Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Neurological Disorders and Stroke (NINDS)
Funding Opportunity Title	Clinical Coordinating Center for the Network of Excellence in Neuroscience Clinical Trials (NEXT - CCC) (U01)
Activity Code	U01 Research Project Cooperative Agreements
Announcement Type	New
Related Notices	September 20, 2022 - This RFA has been reissued as RFA-NS-22-029 June 9, 2011 - See RFA-NS-12-004 Spinal Muscular Atrophy (SMA) Biomarker Study (U01). April 8, 2011 - Notice of Intent to Publish a Request for Applications for a Spinal Muscular Atrophy (SMA) Biomarker Study (U01) and Convene a Related Workshop. See NOT-NS-11-012. December 7, 2010 - Pre-application Meeting for the Network of Excellence in Neuroscience Clinical Trials (NEXT). See Notice NOT-NS-11-005.
Funding Opportunity Announcement (FOA) Number	RFA-NS-11-009
Companion FOA	RFA-NS-11-008, U10 Cooperative Clinical Research Cooperative Agreements RFA-NS-11-010, U01 Research Project Cooperative Agreements
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestics Assistance (CFDA) Number(s)	93.853
FOA Purpose	The purpose of this funding opportunity announcement (FOA), issued by NINDS, is to invite applications to participate as a Clinical Coordinating Center in the Network for Excellence in Neuroscience Clinical Trials. This clinical research network will develop and conduct multiple, scientifically sound, possibly biomarker-informed exploratory clinical trials evaluating the most promising therapies, whether from academic, foundation or industry discoveries. Examples include Phase 2 clinical trials and clinical research studies aimed at validating biomarkers and clinical outcomes in preparation for clinical trials. The network will provide a robust, standardized, and accessible infrastructure to facilitate rapid development and implementation of protocols in neurological disorders affecting adult and/or pediatric populations. While the network will not be specific to one disease, it will have the capacity to coordinate a cadre of specialist investigators to implement studies efficiently in response to disease-specific opportunities. This FOA solicits applications for the Clinical Coordinating Center (CCC). Separate FOAs solicit applications for the Clinical Sites and the Data Coordinating Center (RFA-NS-11-008 and RFA-NS-11-010).

Posted Date	December 7, 2010
Letter of Intent Due Date	February 11, 2011
Application Due Date(s)	March 11, 2011
AIDS Application Due Date(s)	Not Applicable.
Scientific Merit Review	May/June 2011
Advisory Council Review	August 2011
Earliest Start Date(s)	September 2011
Expiration Date	March 12, 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 applications for participation as the Clinical Coordinating Center (CCC) in the Network for Excellence in Neuroscience Clinical Trials. This clinical research network will develop and conduct multiple, scientifically sound, possibly biomarker-informed exploratory clinical trials evaluating the most promising therapies, whether from academia, industry, foundations, the NINDS intramural laboratories or the NINDS translational program. Examples include Phase 2 clinical trials and clinical research studies aimed at validating biomarkers and clinical outcomes in preparation for clinical trials.

The network will provide a robust, standardized, and accessible infrastructure to facilitate rapid development and implementation of protocols in neurological disorders affecting adult and/or pediatric populations. While the network will not be specific to one disease, it will have the capacity to coordinate a cadre of specialist investigators to implement studies efficiently in response to disease-specific opportunities.

The network will include multiple Clinical Sites, one Clinical Coordinating Center (CCC), and one Data Coordinating Center (DCC). The network is designed to increase the efficiency of clinical trials, to facilitate patient recruitment and retention, to increase the quality of neuroscience clinical trials, and to enable public-private partnerships.

BACKGROUND

To translate recent, high quality neuroscience discoveries into better treatments for people burdened by neurological disorders, efficient clinical trials are needed. These trials require cooperation and coordination among investigators, patients and industry partners. Clinical trial networks can increase the efficiency of research by providing infrastructure, centralized resources, and access to patients; however, with more than 400 neurological diseases falling under the auspices of NINDS, creating multiple specialized research networks would not be feasible.

In the traditional model, a consortium of clinical sites is created for each new multi-center trial. This causes redundancy and delays because infrastructure is duplicated. Protracted contract negotiations and approvals at multiple Institutional Review Boards (IRBs) often cause further delays. In addition, there may be loss of expertise as experienced research coordinators move to other fields after a trial is completed. The objective of the network is to increase the efficiency of clinical research through shared infrastructure for NINDS clinical trials.

RESEARCH OBJECTIVES

The network aims to share expertise and infrastructure across diseases, to leverage research resources at clinical sites, and to flexibly take advantage of clinical research opportunities as they arise in different disease areas. Finite resources and especially for rare diseases a small pool of potential participants limit the number of large, confirmatory efficacy (Phase 3) trials that can be conducted at any given time. Therefore, NINDS aims through the network to support exploratory trials that can provide more rapid preliminary testing of new treatments.

The objective of the network is to streamline the implementation of clinical research by using standardized master trial agreements and infrastructure that utilizes a central IRB of record. While NINDS has historically funded trials to test drugs already approved for other indications, the network is designed to assure the broadest access to any new therapies for patients by carrying out trials coming from partnerships between NINDS and industry, foundations, or academia. These trials will be utilizing a variety of the NIH agreement mechanisms (e.g., Cooperative Research and Development Agreements [CRADAs]) that maximize industry participation and support.

It is envisioned that the network will not be "idle" at any time. During the start-up period, as well as during periods of time when new network projects will not take up the entire network capacity, the Clinical Site coordinators and principal investigators will improve the quality and facilitate the implementation of clinical trials at their sites, by offering their support to ongoing NINDS-funded trials and enhancing patient recruitment and retention. The CCC will track site performance as it relates to ongoing NINDS-funded trials.

RESEARCH APPROACHES

Shared Network Infrastructure

This FOA solicits applications for funding of infrastructure for trial coordination. The additional project-specific funds to support the implementation of network protocols will be part of future awards. These funds will be distributed to the Clinical Sites via the 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 network will give preference to clinical sites agreeing to use a central IRB of record, to accelerate IRB approval in multi-center trials. To that effect, the network will use a federated" IRB model. This model gives participating institutions the option to choose one of three tiers of IRB review:

• Tier 1 indicates the reliance on a central IRB as IRB of record;
  
  
• Tier 2 indicates an option to designate a central IRB as IRB of record in addition to a local IRB;
  
  
• Tier 3 indicates the reliance on local review.

The Clinical Sites are strongly encouraged to work with a central IRB of record. The CCC will have to coordinate a central IRB of record and manage all required IRB communication and documentation including but not limited to tracking approval, maintaining regulatory documents, communicating with the local IRBs, and handling adverse event reporting and notifications.

Network Projects

Over the 7-year project period, the network will conduct approximately 5-7 clinical research projects, and will promote the implementation of ongoing NINDS-funded clinical trials. The exact number of protocols supported in the 7-year program will depend on the nature and extent of the investigations proposed and the availability of funds.

To ensure that the network is efficiently using resources from its inception, a short-term clinical research project will begin soon after the network has been established. It is anticipated that this first project will be a biomarker validation study for spinal muscular atrophy (SMA). A separate future FOA will solicit applications for this SMA protocol. Additional trials will be selected from project proposals from industry and academic investigators submitted in response to a second, future FOA that will solicit applications for network Phase 2 clinical trials to be implemented through the network. It is anticipated that at least one of the total trials conducted will be targeted to children.

Following a second level of review by the NINDS advisory council, NINDS will select protocols to be fully developed by a protocol lead team consisting of the Project Director/Principal Investigator (PD/PI), disease-experts as co-investigators, and network representatives.

The final protocol will be approved after technical review by a Protocol Review Committee. A subset or all of the Clinical Sites will then be invited to participate in a given project and will have the option to accept or decline, depending on their capacity, interest, and patient population relevant to the specific protocol. It is also possible that non-network sites may be added ad-hoc for a specific project, for their expertise and patient population to complement network sites.

RESEARCH TOPICS

The Clinical Coordinating Center's Scope of Work includes, but is not limited to:

• Overseeing from conception to analysis/publication the implementation of at least 5-7 complex, multi-center clinical projects over the seven-year funding period;
  
  
• Monitoring human subjects' protection and adequate gender and minority representation among subjects enrolled at network Clinical Sites;
  
  
• Coordinating all network Steering Committee (SC) activities including, but not limited to organizing teleconferences at least twice monthly, and in-person meetings at least three times each year, maintaining documentation such as meeting minutes of SC activities, and coordinating the network SC working groups. SC working groups are established on an as-needed basis to develop and oversee the implementation of specific protocols, and to provide in-depth evaluation and recommendations on such issues as publications/presentations, quality control, conflict of interest, per-patient budgets, and others;
  
  
• Participating in the SC and serving on network SC working groups;
  
  
• Coordinating and documenting all communication, and reporting between the CCC, clinical sites, central IRB of record, and local IRBs, which includes but is not limited to maintaining documentation of IRB initial approvals, amendment approvals, and adverse event and other reports.
  
  
• Establishing standardized master trial agreements with the network Clinical Sites and developing and implementing a plan to reduce the start-up time of each network project through the use of these standardized master trial agreements and the distribution of network approved per-patient cost according to these agreements;
  
  
• Coordinating study drug management, including but not limited to drug and placebo acquisition, delivery plan for bulk drug, secondary packaging/labeling/distribution/storage, blindedness testing, coordinating stability testing and accommodating expiration timelines, and drug accountability;
  
  
• Working with the Project SC and IND sponsor (investigator or industry partner) on obtaining FDA regulatory approval for the trial (IND/IDE or exemption), and on reporting, documenting and coordinating follow-up correspondence;
  
  
• Working closely with the DCC in a collaborative and interactive manner. The CCC and DCC, once selected for potential funding, will submit to the NINDS jointly their respective Standard Operating Procedures (SOPs), revised from the version originally submitted as part of the application, based on their jointly developed collaboration plan. They will also submit a scope of work document that details the division of tasks and responsibilities within the budget they had proposed. It is essential that the tasks required in planning and executing a complex, multi-centered trial be clearly defined, and that the responsibilities of the collaborators (including CCC and DCC) be delineated. It is therefore required that the joint DCC and CCC SOPs and scope of work document show excellent and seamless communication and coordination and reflect an in-depth understanding of the overall operational conduct of a complex, multi-center trial;
  
  
• Providing collaborative leadership to the Clinical Sites, including to potential ad-hoc sites.

During the Conceptual Phase of each potential new network project, the CCC is responsible for:

• Working with potential new network project investigators in determining appropriateness of their project for network infrastructure access;
  
  
• Providing information necessary to the potential investigators as they apply for NINDS funding (e.g., review protocol synopsis and schedule of activities, create project workscope and timeline, ensure the feasibility of the proposed projects by analyzing the numbers of potentially eligible participants at the proposed sites and by including patient representatives in the conceptual process);
  
  
• If needed, the CCC will support project investigators in the IND/IDE submission.

During the Planning Phase of approved network projects, the CCC is responsible for:

• Working with project lead team of investigators to finalize the protocol and consent form;
  
  
• In collaboration with the DCC, working on case report forms (CRFs);
  
  
• Participating in site selection;
  
  
• Developing a written, detailed patient recruitment plan, with attention to adequate minority recruitment;
  
  
• Monitoring the IRB approval process and promoting rapid approval through well-developed and complete documentation at the initial submission, and through rapid and comprehensive responses to any IRB comments or concerns;
  
  
• Collecting regulatory documents (1572 forms, curricula vitae, Good Clinical Practice [GCP] certifications, etc.);
  
  
• Finalizing details of per-patient payments to sites within approved budget, developing site payment schedule, finalizing subcontracts with sites per master trial agreements;
  
  
• Finalizing study drug packaging and labeling;
  
  
• Holding investigator meetings and ensuring initial study personnel training for GCP and protocol adherence;
  
  
• Working with the DCC as they establish a trial database.

During the Implementation Phase, the CCC is responsible for:

• Overseeing the enrollment of eligible subjects;
  
  
• Tracking enrollment and retention and developing outreach interventions as needed;
  
  
• Distributing study drug to sites;
  
  
• Working with sites to ensure appropriate protocol implementation and adherence to protocol and GCP;
  
  
• Answering queries from the sites regarding protocol, drug dose adjustments, adverse events, premature withdrawals, etc.;
  
  
• Conducting site visits, as needed;
  
  
• Supporting the DCC in their monitoring and data quality assurance procedures.

During the Analysis and Publication Phase, the CCC is responsible for:

• Assisting the DCC and sites in resolving final queries, finalizing reporting to the FDA and IRBs;
  
  
• Coordinating the communication of the trial results to the investigators, patients and public;
  
  
• Working with the DCC and network investigators in the publication of the primary and, if applicable, secondary manuscripts.

Network Structure and Management

The NINDS Network of Excellence in Neuroscience Trials will include: one Data Coordinating Center (DCC), one Clinical Coordinating Center (CCC), and up to 25 Clinical Sites. Investigators at the NIH Clinical Center may function as an additional clinical site.

• 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 NINDS partner, consistent with the Cooperative Agreement mechanism. The NINDS will appoint a Scientific Advisory Board (SAB). The SAB is an external group of experts who will review the network Program and advise the network investigators and the NINDS.
  
  
• A Steering Committee (SC) composed of three principal investigators representing the Clinical Sites, the DCC PI, the CCC PI, plus the PIs of active network projects and the NINDS Project Scientist will be the main governing body of the network. NINDS will appoint an SC Chair to preside over SC meetings and serve as the SC representative to the SAB.
  
  
• All major scientific decisions will be determined by majority vote of the SC;
  
  
• Each SC member will have one vote; the SC Chair will cast a vote in case of a tie;
  
  
• The protocol lead PIs of approved network protocols will become SC members for the duration of the project they are leading;
  
  
• The initial three Clinical Site representative PIs will be appointed by NINDS to the SC for a 2 to 3-year term;
  
  
• The second slate of SC investigator-members will consist of the highest overall enrolling investigator and two investigators elected by their peer investigators to a 2-year term. For continuity, one of the three initial SC investigator members will serve on the committee for 2 years, and two will serve on the committee for 3 years, so that not all tenures expire at the same time;
  
  
• It is anticipated that the SC will meet two times per month by telephone conference call and at least three times per year by in-person meetings;
  
  
• The SC will have primary responsibility for network governance, and will advise on prioritizing protocols. SC working groups will be established by the SC to perform specific functions, such as, for example:
  
  
  • Protocol review, publications and presentations;
  • Per-patient budget approval;
  • Quality control assurance;
  • Conflict of interest.
    
    
• The DCC will support protocol development and implementation with regards to statistical design, data management, data quality assurance, and analysis;
  
  
• The DCC will also initiate and coordinate activities to promote standardization of data elements using the NINDS common data elements (CDEs) when available, or help develop common data elements and standardized protocols. See RFA-NS-11-010 for more details describing the responsibilities of the network DCC.
  
  
• The CCC will provide overall clinical coordination as described above.
  
  
• The Clinical Sites will facilitate efficient project start-up; will collect high quality data in adherence to the protocol and in compliance with the rules and regulations governing clinical research.
  
  
• The Clinical Sites will also participate in network-wide training, communications, and network SC activities, including network-SC working groups, as needed.

Funding Instrument	This FOA will use the NIH U01 research Project Cooperative Agreement award mechanism (U01). In the cooperative agreement mechanism, the PD(s)/PI(s) retain(s) the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the PD(s)/PI(s), as described under the Section VI.2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".
Application Types Allowed	New The OER Glossary and the PHS398 Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The total amount of funding that NINDS expects to award through this announcement is up to $18.5 Million. The anticipated number of awards is one (1). 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 expected direct cost amount for individual awards is up to $1.75 Million annually for 7 years. Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004. 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.
Award Project Period	This is a one-time solicitation to fund the network for 7 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)
• Eligible Agencies of the Federal Government
• 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 Organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations 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 Directors/Principal Investigators (PD/PIs) 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 Project Director/Principal Investigator (PD/PI) 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 PHS398 Application Guide.

The PD/PI for the network Clinical Coordinating Center will be a clinical trials expert with a track record in successfully coordinating and implementing complex, multi-center clinical trials in the neurosciences.

• Institutions will be required to 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).
  
  
• 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 clinical research expertise they could draw upon on an as-needed basis, as well as any research resources they have established at their institution.
  
  
• Applicants should describe the SOPs they have in place and the processes they currently apply when coordinating multi-center projects.
  
  
• Applicants should document their timelines in project management of recent trials, and describe the collaborative leadership structure used in recent multi-center trials they have coordinated.
  
  
• Applicants are encouraged to provide examples and describe features of investigator meetings and research team training sessions they have organized.

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

Only one CCC application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed. However, applicants may apply for an award for the DCC or Clinical Site (separate FOAs) as well as for an award under this FOA.

Awards for a CCC and a DCC will not be made to the same Principal Investigator, to ensure that data analyses and data acquisition are performed independently.

Awards for a CCC and a Clinical Site may be made to the same institution.

However, it is preferred that the CCC and a Clinical Site at the same institution be led by separate investigators, to ensure that the CCC activities as well as the local Clinical Site activities receive full attention.

This section contains other eligibility criteria, if applicable (e.g., if entities have violated a particular statute).

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. Resubmission applications are not permitted in response to this FOA.

Renewal applications are not 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.

A letter of intent is required.

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 PI;
Names of other key personnel;
Participating institutions;
Number and title of this funding opportunity.

The letter of intent should be sent to:

Petra Kaufmann, MD
National Institute of Neurological Disorders and Stroke
National Institutes of Health
6001 Executive Blvd., Room 2116
Bethesda, MD 20892-9520 (Express/Courier: Rockville, MD 20852)
Telephone: (301) 496-9135
Email: [email protected]

Pre-Application Meeting: The NINDS anticipates holding a technical assistance meeting in January 2011 (now December 17, 2010 per NOT-NS-11-005), through a teleconference to which all interested prospective applicants are invited. Program and review staff will make presentations that explain their goals and objectives for the NEXT Initiative and answer questions from the attendees. Prospective applicants are urged to monitor the NIH Guide for Grants and Contracts regarding a Notice for the date and time of the meeting (http://grants.nih.gov/grants/guide/index.html).

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 must be followed, with the following exceptions or additional requirements:

• Research Strategy section is limited to 30 pages. Applications received that exceed these page limitations will not be reviewed.

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

Applications should include the following information in the relevant subsections:

1) Leadership and Operations Plan

The PD/PI should describe in the Approach section of the Research Strategy, how clinical trials and research will be strategically supported by the network Clinical Coordinating Center. The PD/PI should describe the expertise and track record of the research staff, the CCCs 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 CCC. Note that the CCC will be responsible for registering all trials with http://www.clinicaltrials.gov.

2) Collaboration Plan

In the relevant sections of the Biosketch, Resources/Facilities and the Research Strategy or (where applicable), in the Multiple PD/PI Leadership Plan, applicants should state their general support of collaborative research and their willingness to participate in a collaborative and interactive manner with the Clinical Sites, the Data Coordinating Center, and NINDS and its partners (both academic and industry 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., experience in clinical trial collaborations with industry partners or patient groups). The applicant should indicate how potential network project investigators (from academia or industry) will be motivated to work with the network, supported in the conception phase, and integrated into the network in the planning and implementation phases.

3) Recruitment and Outreach Plan

In the Approach section of the Research Strategy, the PD/PI should describe plans for supporting recruitment of patients at the clinical sites, including plans to optimize minority recruitment. Additional details on recruitment plans may be provided in the Human Subjects section of the application, as appropriate. Prospective recruitment plans should be established for each project and the PD/PI should indicate how outreach into the community at the Clinical Sites, to referring physicians and patients will be encouraged, what actions and materials will be used to support recruitment of patients, and how patients will be included in the conception, planning and implementation of trials so that a strong partnership between investigators and patients can serve as a foundation for successful trial recruitment and retention.

4) Leveraging Local Clinical Research Resources Plan

In the Resources/Facilities section of the application, the PD/PI should describe how local clinical research resources such as equipment, space and research staff will relate to the network CCC activities, and, if applicable, how the network will integrate Clinical and Translational Science Award (CTSA) resources.

5) Plan to Increase the Quality and Efficiency of the Clinical Research Enterprise at the Clinical Sites

For new trials, describe CCC plans to reduce start-up time by increasing the efficiency of contracting and IRB review through use of standardized master trial agreements and federated IRB models. If applicable, describe additional measures in the Research Strategy section that would increase the efficiency of ongoing NINDS-funded clinical research, even if outside of the network. Describe other plans to increase the quality and efficiency of clinical trials. Describe how protocol adherence and data quality will be maximized in collaboration with the Clinical Sites.

6) Performance Monitoring and Potential Interventions Plan

For new and potentially also for ongoing NINDS-funded trials, the application should describe in the Approach section of the Research Strategy, how the CCC will monitor performance and collect data on start-up, recruitment and retention, as well as data quality for NINDS-funded clinical trials at the Clinical Sites.

7) Training Plan

The network presents a rich environment for young investigators to be exposed to and develop additional research skills and to assist them in progressing to more senior status. In the Approach section of the Research Strategy, describe the plans to reach out to young investigators.

8) Clinical Coordination and Project Management Plan

Leading the network CCC will be a complex and time-consuming undertaking, and applicants must have the necessary experience and expertise to coordinate multi-center clinical trials in pediatric and adult patients with neurological disorders. Therefore, a listing of current and up to five of the most recently completed trials that the CCC applicant has coordinated must also be provided in the 30 page Research Strategy.

The standard operating procedures (SOPs) used by the CCC in the implementation of multi-center clinical trials, including, but not limited to SOPs describing regulatory document collection, IRB approvals, study drug management, procedures to minimize bias and maintain blinding, recruitment plans, retention plans, data sharing plans, safety monitoring plans, etc., should be included under Research Strategy. Plans directly related to participants such as adverse event monitoring, may be included in the Human Subjects section, as necessary.

In the Research Strategy section, applicants should include a table with a brief description of current and up to five most recently completed trials that the CCC has coordinated, indicating:

• the intervention;
• the funding source;
• the sponsor of the IND;
• the drug distribution center;
• the data management center;
• the number and location of sites (US and/or other countries);
• the number of patients;
• the length of follow-up;
• time to first subcontract executed (starting from award date);
• time to last sub-contract executed;
• time to IRB at CCC site;
• time to first IRB approval at any consortium site;
• time to last IRB approval at a consortium site;
• time to first patient screened;
• time to first patient randomized;
• overall recruitment rate;
• proportion of patients lost to follow-up;
• time from last patient last visit to database lock.

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.

The following items are recommended for inclusion as the Appendix:

• In accordance with the NIH policy on appendix materials (NOT-OD-07-018), when a free, online, publicly available journal link in not available, applicants should provide up to 3 manuscripts either accepted for publication or in press that highlight recently coordinated trials;
• One sample protocol and set of Case Report Forms (CRFs).

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 and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Qualifications and Experience

• Applicants should have demonstrated leadership in the design and conduct of clinical trials, as well as a track record in successfully coordinating and implementing complex, multi-center clinical trials, working with academic, foundation and industry partners, and include this in the Multiple PD/PI Leadership Plan.
  
  
• Applicants should describe specific experience with international trials.

Collaboration

• In the Budget Justification section, 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.
  
  
• In addition, applicants should discuss in the Approach section of the Research Strategy, their (and their institutions') willingness to establish master trial agreements with each Clinical Site, so that the per-patient cost associated with specific network protocols can be efficiently administered.
  
  
• In the Approach section of the Research Strategy, applicants and their institutions should also indicate their willingness to coordinate a central IRB model, as described above (Part 2. Section I. "Research Approaches").
  
  
• CCC applicants should be able to work closely with the DCC.
  
  
• The CCC and DCC have to collaborate in reporting results in a timely manner to http://www.clinicaltrials.gov.

Links with NIH Resource Centers

Applications from institutions that have a General Clinical research Center (GCRC) or Clinical and Translational Science Award (CTSA) funded by the NIH National Center for Research Resources should identify the resources that could be available to support the proposed network CCC, commenting particularly on those aspects that will enhance their programmatic and scientific efficiency in the Resources/Facilities section of the application. In such a case, a description of the GCRC or CTSA and how the applicant proposes interacting with it should be included, as well as letter of agreement from either the GCRC/CTSA Program Director or PI included in the Letters of Support section of the application Having a GCRC or CTSA at the institution is not a requirement for application.

Budget

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

All activities related to coordinating at least 5-7 clinical research studies, should be budgeted, including:

• Start-up activities;
• Regulatory approvals;
• Training and investigator meetings, SC and other leadership committee functions;
• Site visits;
• Communication, documentation and reporting required to operate a central IRB of record;
• Study drug management;
• Collecting regulatory documents;
• Working with potential network investigators in the protocol conception development and implementation phases.
• In addition, administrative tasks related to subcontracting with Clinical Sites, monitoring recruitment and protocol adherence, and tracking and reporting performance must be budgeted.
  
  
• The budget should also include travel costs for at least two CCC team members to attend SC meetings in Bethesda, MD three times each year, plus other travel related to network operations, including at least one visit to each Clinical Site throughout the funding period, for training purposes, plus two annual trips to DSMB meetings.
  
  
• The CCC budget should also include support for two training and SC meetings. The Clinical Site budgets will include travel for two site personnel to travel to meetings in Bethesda, MD three times each year. The CCC budget should include all other costs for planning and implementing meetings.
  
  
• The actual per-patient compensation to the sites (for enrolling patients and for collecting data) for each trial to be conducted within the network will be provided by separate sources of funding and do not need to be included in this budget. However, the CCC should budget for administrative tasks related to distributing these funds.

The total budget should not exceed $1.75 Million direct costs per year in years 1-7 (all of which will be 12-month project years). The release of funds will be milestone-driven, according to milestones pre-specified in the Notice of Grant Award. Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation (see NOT-OD-05-004).

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 project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

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

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/PIs, 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 coordinating multicenter clinical trials?

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 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?

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 letters that demonstrate support via such means as additional protected time, departmental research leadership position, facilities, space, or resources for the PD/PI and/or Clinical Site?,
  
  
• Does the application provide assurance that the institution will be able to coordinate and utilize a central IRB of record as well as standardized network master trial agreements for per patient cost of clinical programs?
  
  
• Does the applicant have a track record of achieving relatively short trial start-up times with regard to contract negotiations, IRB approval times, study personnel training?

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/priority score, but will not give separate scores for these items.

• Do the investigators provide consistent evidence for collaborative leadership, and is there evidence of experience in and willingness to participate appropriately in a collaborative program as described in this FOA?
  
  
• Does the investigator have a successful track record in neuroscience clinical trial coordination?
  
  
• Are proposed interactions/communications between the CCC and the DCC, clinical sites and the community (e.g., referring physicians and patient populations) clearly described and creatively optimized?
  
  
• Is the applicant’s institution willing to work with a centralized network IRB and through standardized master trial agreements for the per-patient cost of network trials?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable.

Renewals

Not Applicable.

Revisions

Not Applicable.

As applicable for the 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/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 Scientific Review Branch (assignments will be shown in the eRA Commons), in accordance with NIH peer review policy and procedures, using the stated review criteria.

As part of the scientific peer review, all applications will:

• 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.
• 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 submitted in response to this FOA . Following initial peer review, recommended applications will receive a second level of review by the National Advisory Neurological Disorders and Stroke Council.

For this particular announcement, 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.
• Strong track record of collaborative leadership and successful coordination of large, multi-center clinical trial teams;
  
  
• Willingness to work collaboratively with clinical sites, with the data coordinating center, with partners from academia and industry, and with clinical researchers from a wide range of disease-specific backgrounds;
  
  
• Track record in coordinating an experienced clinical research team that may include but is not limited to clinical coordinators, project managers, drug supply specialists, contracting and accounting specialists, regulatory affairs specialists, and administrative support staff;
  
  
• Performance in coordinating recent and current multi-center clinical trials, both NINDS-funded programs and multi-center clinical trials funded by sponsors other than NINDS;
  
  
• Ability to begin operations immediately;
  
  
• Willingness, and evidence of potential, to participate in all aspects of the network program, including investigator meetings, protocol development, Steering Committee (SC) responsibilities including SC working groups, and participation in teleconferences and in-person meetings;
  
  
• Agreement to accept the Cooperative Agreement Terms and Conditions of Award delineated in this FOA (see Section VI.2.A);

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

• Coordinating all aspects of network research protocols, including monitoring trial participant safety, implementation of network protocols in accordance with GCP and other regulatory requirements, participant recruitment and retention, reporting to the NINDS, and working with the DCC in reporting to the DSMB and to clinicaltrials.gov.
  
  
• 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 the CCC. 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 Steering Committee (SC) composed of three Clinical Site PIs representing the Clinical Sites, the DCC PD/PI, the CCC PD/PI, plus the PD/PIs of active network projects and the NINDS Project Scientist will be the main governing body of the network. NINDS will appoint a SC Chair.
  
  
• The CCC PD/PI and other key staff are expected to participate in all network teleconferences and investigator meetings. They are also expected to serve on SC working groups established on an as-needed basis to develop and oversee specific protocols, and to provide in-depth evaluation and recommendations on such issues as publications/presentations, protocol implementation, quality control, conflict of interest, and others.
  
  
• Each full member will have one vote. Awardees will be required to accept and implement policies approved by the SC.

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 Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

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. Petra Kaufmann
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.