Purpose

The purpose of this funding opportunity announcement (FOA) is to solicit applications for the Coordinating Center (CC) for the Stroke Preclinical Assessment Network (SPAN). SPAN will support late-stage preclinical studies of putative neuroprotectants to be given prior to or at the time of reperfusion, with clinically relevant long-term outcomes and comorbidities. Parallel testing of the most promising interventions will help to determine if an intervention can improve outcome as compared to reperfusion alone and/or extend the therapeutic window for reperfusion, and if so, guide the selection of the best agent(s) to transition to future Phase II clinical trials (to be conducted through StrokeNet). SPAN will consist of one CC and up to 6 network sites; this infrastructure is expected to test up to 6 compounds/interventions in animal models of transient cerebral ischemia. The SPAN program will not support any human subjects research.

Background

Until 2015, intravenous recombinant tissue-type plasminogen activator (rt-PA) was the only FDA-approved therapy for acute ischemic stroke. Despite its overall efficacy and safety, rt-PA presents some limitations, such as increased risk of hemorrhagic transformation, a narrow time window of few hours from stroke onset, and a low success rate in lysing large clots. Over the past few years, acute endovascular therapy (EVT) with stent-retriever devices and access to advanced imaging modalities have transformed the standard of care, offering the opportunity to improve outcome significantly in selected patients that have salvageable tissue treated as late as 16-24 hours after their stroke. Despite the success of EVT in clinical trials, many patients still experience neurological deficits following therapy; thus, there is a need to develop adjunctive approaches to improve long-term outcomes. These recent advances offer a new and timely opportunity to further evaluate the potential benefit of neuroprotective agents in the context of mechanical revascularization.

The 2012 NINDS Stroke Research Priorities Meeting identified several priorities that are relevant to the proposed initiative:

• Accelerating the Translation of Stroke Research in Preclinical Animal Models into Clinical Studies of Highly Promising Treatments;
• Preclinical and Clinical Studies to Improve Early Reperfusion Therapy and Establish the Limitations of Late Reperfusion Therapy;
• Preclinical and Clinical Studies to Achieve Robust Brain Protection.

Furthermore, this initiative builds on the recent NINDS-sponsored workshop "Translational Stroke Research: Vision and Opportunities", which recommended that preclinical multi-laboratory trials of a putative treatment may be valuable before investing in a clinical trial.

Research Objectives

The overall goal of this program is to create a virtual preclinical stroke network to support late stage preclinical studies of potential neuroprotective strategies to be given prior to or during reperfusion. SPAN will test in parallel up to 6 compounds/interventions in animal models of transient cerebral ischemia following the same rigor and methodology characteristic of clinical trials. The parallel testing of multiple interventions, including an adaptive design approach that will eliminate compounds that do not demonstrate sufficient promise, will allow the identification of the most promising candidates to advance to clinical testing. Only drugs/ interventions that are supported by robust and rigorous preliminary data, have been shown to be safe in humans, and are likely to be ready for clinical testing by the end of the award will be eligible to be tested through the SPAN network.

The SPAN CC will contribute to these objectives by providing scientific and organizational leadership for implementation of preclinical protocols to be conducted within the network sites. The CC will promote high quality and efficiency in study execution and provide a central resource for protocol development, drug acquisition, formulation and distribution, study administration, data management, and statistical analysis. The CC additionally organizes the SPAN governance committees and oversees quality assurance for network performance. The CC is encouraged to be innovative in improving research efficiency and quality.

SPAN Organization

The Coordinating Center (CC) will provide scientific and organizational leadership to SPAN to achieve both efficiency and excellence in the implementation and performance of the neuroprotection protocols. The CC will work collaboratively with the network sites and NINDS to provide overall study coordination, including oversight of study protocols, monitoring of the individual sites, data management, data sharing, and reporting. Additionally, the CC will be responsible for acquisition, formulation, and distribution of active and control compounds. Candidate compounds/interventions for the network will be proposed through the companion FOA RFA-18-033 and selected following peer review.

Each Network site will propose one promising neuroprotectant to be tested in SPAN and will test, in a controlled, randomized, and blinded fashion, up to 6 interventions in parallel, including their own. The roles and responsibilities of the network sites are described more fully in the companion FOA, RFA-NS-18-033.

Expectations of the SPAN Coordinating Center

The CC provides scientific and organizational leadership to facilitate the conduct of preclinical studies within SPAN. The CC is the administrative center of the network, with responsibility for maintaining the network’s infrastructure relevant to best practices consistent with those routinely used in clinical trials. Expertise in preclinical models of transient cerebral ischemia is not a requirement for the CC. However, the CC is required to have strong expertise in data management; statistical analysis, including adaptive trial design; drug formulation; complex project coordination; randomization; and blinding. Expertise in stroke research is desirable, but not required. In addition, the CC leads and manages the key SPAN governance committees: SPAN Steering Committee and the External Advisory Board (described below). Specific activities could be performed through subcontracts, but the activities and the facilities need to be clearly described in the application.

Examples of responsibilities of the CC include the following:

• Providing scientific leadership and regular communication to SPAN sites regarding protocols and study progression
• Overseeing multiple concurrent protocols
• Managing ongoing operational issues, such as subcontracts, protocol-specific site training, and site monitoring
• Developing and implementing investigator and staff training programs
• Organizing and implementing investigator meetings, including an annual in-person meeting to enable exchange of data and enhance synergy across the network
• Overseeing drug/intervention and placebo control acquisition and distribution as needed
• Developing operational guidelines and assuring compliance with protocols and reporting
• Developing a plan for conflict resolution
• Coordinating editorial and manuscript preparation
• Managing data and resource sharing activities
• Analyzing data and adjust protocols and interventions to be performed at each site, based on the adaptive design approach
• Monitoring compliance with milestones to be determined at the time of the award.

The CC is expected to coordinate with the network sites to ensure that testing of the selected drugs/ intervention will start no later than 1 year after the award and will be completed in the remaining 2 years of the award.

SPAN Network Committees

1. The governing body of the network will be a Steering Committee, appointed by the CC in conjunction with NINDS, that will consist of the PD/PI of the CC, the PD/PI of each of the network’s testing sites, NINDS Program staff and 3 representatives from the NIH Stroke Clinical Trials Network (StrokeNet) Steering Committee (to facilitate a potential transition to clinical trials to be conducted in the future, if the intervention is successful in SPAN). The NINDS Director has the right to supersede any decision by the network at any time.

2. An independent External Advisory Board, appointed by and reporting to NINDS, will comprise basic and clinician scientists with expertise in neuroprotection, representatives from pharmaceutical and biotech industry, and experts in regulatory affairs, statistics, and clinical trial design.

.

The CC will be responsible for managing the logistics of committee activities, such as scheduling, soliciting agenda items, finalizing and distributing agendas, arranging and leading monthly teleconferences, preparing minutes, and making logistic and financial arrangements for annual in person SPAN meetings, including meeting space, accommodation, travel, per diem reimbursement, etc.

National Institute of Neurological Disorders and Stroke

The NINDS will be responsible for organizing and providing overall support for the SPAN network. NINDS Program and Grants Management staff will be responsible for the overall management of the SPAN network. In addition to regular grant stewardship, an NINDS Project Scientist will be involved substantially with the awardees as an NINDS partner, consistent with the Cooperative Agreement mechanism.

Applicants are strongly encouraged to consult with NINDS Scientific/Program Staff early during the planning phase of their application (See Agency Contacts, Section VII).

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
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

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

Applicant Organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA. All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims: State the specific aims to outline a clear strategy for implementing the goals of this FOA.

Research Strategy: Organize the Research Strategy by Significance, Innovation, and Approach. A milestone plan, under separate heading, must be included in the approach.

Significance: The Significance section should describe how the proposed CC infrastructure and organization will address primary goal of rapid identification of neuroprotective interventions as adjunctive therapies to recanalization. This section should provide justification and rationale indicating that the proposed team and plan can fulfill the role of the CC as the network’s information, data, and administrative hub, and will work closely, collaboratively and effectively with the individual projects PIs and their teams, the NINDS/NIH Program staff and the Steering Committee and External Advisory Board.

Innovation: Describe the leading and innovative tools and approaches that the proposed CC offers to the network in terms of data management, communication strategies, information technology, approaches to organization of meetings and conference calls, drug development and distribution, and other activities under the purview of the CC.

Approach: The approach should address administrative commitment, resources and ability to carry out the duties of the CC. The application must describe the current and/or planned organizational structure under which it proposes to operate. If the CC has more than one component/affiliate institution, describe the relationship of component(s)/affiliate(s) to each other and to the CC. Include the distance between these institutions (including administrative offices and shared resources) and location of proposed personnel.

Relevant Accomplishments: describe the group’s accomplishments relative to implementing procedures routinely used in clinical trials, such as randomization, blinding, monitoring of the sites, that would be applicable to the SPAN network. Describe relevant experience in drug procurement and formulation.

Describe the overall management plan, organizational hierarchy of the CC, its administrative structure, the communication plan, and the conflict resolution plan. Describe how the CC will organize, coordinate and administratively drive network-specific activities including: establishing the Steering Committee (the External Advisory Board will be established by the NINDS); organizing the logistical components of all committee activities including, for example, scheduling, soliciting agenda items, finalizing and distributing agendas, arranging calls including conference calls, minutes (drafting, editing based on input, and finalizing); all logistic and financial requirements for in person network meetings including meeting space, accommodation, travel, per diem reimbursement, etc.; required sharing activities. The application should describe how the CC will work with multiple and de-centralized investigators and schedule large (dozens of participants) interactive conference calls including visual support. Indicate how members will be selected for Committees by nomination and vote. All Committees will be formed by 3 months after Notice of Grant Award. SPAN Committees will include members from both the individual sites/projects of the network and the CC, as well as representation from the NINDS/NIH.

Describe how the CC will establish infrastructure, including processes for real-time data entry, data management, including quality assurance (e.g. accuracy, completeness, and internal consistency), and sharing (within the network and with external scientists after appropriate publication). Indicate how the CC will facilitate efficient and accurate incorporation of new and/or extant data via electronic data entry from remote locations. Indicate how the CC will assist in developing and build into its infrastructure the core set of data elements agreed upon by the network. Detail how the CC will harmonize compatible but not identically coded extant data across platforms for sharing and metanalyses. The application should explain the CC’s statistical expertise to help inform adaptive design and analyses. A plan for how the CC will monitor performance across the individual network sites should be described.

Milestone Plan: The application must include a 1-year well-defined Milestone Plan in the approach section with a timeline for establishing the CC to full functionality within the expectations indicated below. Milestones should be unambiguous, quantifiable, and justified. The final milestone plan is subject to concurrence by the CC and NINDS. The timeline and milestones will be used to evaluate applications both in peer review and also in consideration of the awarded CC for funding of non-competing award years. See the section below on Cooperative Agreement Terms and Conditions of Award for specific guidance on content and timing of Milestones. The final Milestone plan is subject to approval by NINDS.

• Initiate calls to organize the Steering Committee by 1 month after Notice of Grant Award.
• Organize the SPAN Kickoff Meeting to be held within 4 months of receiving a Notice of Grant Award.
• Organize Annual meetings (1 per year within a month of annual date of original Notice of Grant Award).
• Develop and test the CC’s information technology infrastructure for receiving real-time data entry from multiple remote locations (including imaging data) by the end of year 1.

  The application should describe the strategy used by the PD/PI and Institutional official to delegate leadership responsibility and how the responsibility is delegated among key/senior individuals. The qualifications, experience, and proposed duties of all proposed support personnel should be described.

  Applicants should provide clear scientific, administrative, and institutional commitments to collaborate with other funded network project investigators/sites to maximize time- and cost-efficiency of testing in parallel up to 6 various neuroprotective interventions.

Letters of Support: If the application includes subcontracts or subawards for particular components of the CC’s operational structure, it should include letters of support from consultants and/or sub awardees detailing the required expertise and available infrastructure. If an application plans to utilize the infrastructure or resources of existing projects, whether funded by the NINDS, other governmental or nongovernmental entities, letters of support detailing the terms of collaboration and data sharing must be included, and must be from the appropriate authority/ies (e.g. institutional/foundation official, funding sponsor, and/or lead PI of the parent activity). Any conflicts with any known entities should be revealed and discussed. Review and approval for the use of samples and data must be completed and a letter of approval must be obtained prior to submission of an application under this FOA.

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. The sharing infrastructure and protocols must be able to facilitate sharing within the network and with scientists outside of the network (after projects are completed).

Applications must include a clear administrative and institutional commitment to data sharing, including strategies and ability to share raw data, images, and protocols both within the network as well as with other investigators. Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide. When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed. Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy. Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the center 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 center proposed). Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the proposed Center address the needs of the research projects/network that it will coordinate/administer/serve? Is the scope of activities proposed for the Center appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research projects/network? Is there evidence that the proposed team and plan can fulfill the role of the CC as the network's information, data, and administrative hub? Does the CC demonstrate clear understanding of the SPAN goals and the commitment to work closely, collaboratively and effectively with the individual projects' PIs and their teams, the NINDS/NIH Program staff and the Steering Committee and External Advisory Board?

Does the application propose novel organizational concepts, management strategies, or instrumentation in coordinating the research projects/network/ the Center will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts, management strategies or instrumentation proposed?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex and age, for studies in vertebrate animals?

Will the institutional environment in which the Center will operate contribute to the probability of success in facilitating the research projects/network it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Center proposed? Will the Center benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

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

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials. For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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

Not applicable.

Not applicable.

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 score.

Not applicable.

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

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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

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 score.

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:

The SPAN Network CC PD/PI(s) will have the primary responsibility for:

• Designing, leading and implementing all aspects of the SPAN CC as described in this FOA;
• Setting milestones, subject to concurrence of the CC Program Director;
• Ensuring adherence to all applicable NIH/NINDS policies including for data sharing and reporting and assisting sites with development of standard protocols involving vertebrate animals;
• Analyzing and publishing results, interpretations and conclusions of the studies, in collaboration with the network PIs, and providing overall scientific and administrative leadership for the research projects;
• Establishing and overseeing the SPAN Steering Committee;
• Reporting to NINDS regarding timeline and milestone achievement and annual progress reports;
• Coordinating and monitoring all projects within the SPAN Network;
• Scheduling and participating in all network teleconferences and investigator meetings, including Kickoff and Annual in-person SPAN network meetings;
• Coordinating and facilitating development and implementation of network-specific protocols and policies (e.g. regarding pre-registration, randomization, blinding, publication, sharing, etc., as applicable);
• Providing appropriate guidance to network sites/PIs;
• Providing quality assurance monitoring.

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

NINDS program staff will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination. However, the role of NINDS Project Scientists will be to facilitate and not to direct or drive the activities. The NINDS will establish a Steering Committee to assist in determining, in conjunction with the External Advisory Board Committee, the broad direction of the network.

NINDS Program staff will:

• Contribute to the adjustment of research protocols or approaches as warranted;
• Contribute to develop final milestones for the study;
• Serve as a liaison between the awardees, the NINDS Advisory Council and the larger scientific community;
• Establish the External Advisory Board Committee;
• Serve on committees of the SPAN network as appropriate;
• Assist in promoting the availability of data and resources developed during the project to the scientific community at large;
• Assist awardees in the development, if needed, of policies for dealing with situations that require coordinated action;
• Retain the option to recommend the withholding or reduction of support from any cooperative agreement that either substantially fails to achieve its goals agreed to at the time of award, fails to maintain state-of-the-art capabilities, or fails to comply with the Terms and Conditions of the award including biospecimen and data sharing requirements.

Areas of Joint Responsibility include: None. All responsibilities are divided between awardees and NIH staff as described above.

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: (1) a designee of the Advisory Committee chosen without NIH staff voting, (2) one NIH designee, and (3) a third designee with expertise in the relevant area who is chosen by the first two members; in the case of disagreement between the first two members, the third member will be chosen by the Consortium-elected Chair of the Steering Committee. This 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 eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267 Francesca Bosetti, Pharm.D., Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-1431
Email:frances@mail.nih.gov Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
Email:nindsreview.nih.gov@mail.nih.gov

Tijuanna Decoster, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email:tijuanna.decoster@nih.gov Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.