Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Neurological Disorders and Stroke (NINDS)

Funding Opportunity Title
Data Coordinating Center for the Network of Excellence in Neuroscience Clinical Trials (NEXT - DCC) (U01 Clinical Trial Not Allowed)
Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type
Reissue of RFA-NS-11-010
Related Notices

NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022

Funding Opportunity Announcement (FOA) Number
RFA-NS-22-030
Companion Funding Opportunity
RFA-NS-22-029 , U01 Research Project (Cooperative Agreements)
RFA-NS-22-031 , U24 Resource-Related Research Project (Cooperative Agreements)
Assistance Listing Number(s)
93.853
Funding Opportunity Purpose

The purpose of this funding opportunity announcement (FOA), issued by NINDS, is to invite applications to participate as a Data Coordinating Center (DCC) 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, phase 2-3 trials if warranted by the nature of the studied population (such as rare diseases), and platform trials where applicable. in addition, the DCC will offer data coordination and statistical support to the Gene Therapy Consortium organized by the CCC.

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 DCC. Separate FOAs solicit applications for the Clinical Sites and the Clinical Coordinating Center.

Key Dates

Posted Date
September 20, 2022
Open Date (Earliest Submission Date)
October 21, 2022
Letter of Intent Due Date(s)

30 days prior to application due date

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
November 21, 2022 Not Applicable Not Applicable March 2023 May 2023 July 2023

All applications are due by 5:00 PM local time of applicant organization. 

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

Expiration Date
November 22, 2022
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose:

This funding opportunity announcement invites applications for participation as the Data Coordinating Center (DCC) in the Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT). The purpose of the network is to efficiently conduct multiple, scientifically sound, possibly biomarker-informed exploratory clinical trials evaluating the most promising therapies, and to facilitate collaborations between academia, industry, non-profit foundations, government organizations, and other possible stakeholders. The main focus of the network is the conduct of phase 2 clinical trials. Studies of biomarker validation are also eligible, if a multicenter network setting is necessary. In addition, the network will serve as the vehicle for the conduct of early clinical trials of gene therapy for ultra-rare neurological disorders. Where the nature of the study population warrants it, phase 2-3 trials are acceptable.

The network provides 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 is not specific to one disease, it has the capacity to coordinate a cadre of specialist investigators to implement studies efficiently in response to disease-specific opportunities. The network will set up master protocols if warranted for specific patient populations or therapeutic assets.

Background:

NeuroNEXT was established in 2011, in order to provide an efficient structure for the conduct of high-quality, collaborative clinical trial studies, focusing on the phase 2 clinical trial space, as a particularly challenging and impactful area of clinical research. 11 studies have been or are being conducted in the network since inception. A recent network review has highlighted opportunities for improvement and progress, which are reflected in this FOA.

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 trials that can provide more rapid preliminary testing of new treatments.

The network will streamline the implementation of clinical research by using standardized master trial agreements and infrastructure that utilizes a central IRB of record, and 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.

Shared network infrastructure:

This FOA encourages applications for funding of infrastructure for data and statistical coordination. The additional project-specific funds to support the implementation of network protocols will be part of future awards. 

Responsibilities of the DCC include the following:

  • The DCC will provide full statistical support from trial conception, design, implementation (including but not limited to randomization), to interim analysis, final analysis, and publication; The DCC will lead the design and implementation of master protocols where appropriate for specific studies;
     
  • The DCC will also provide full data management support from conception, planning, building a trial database with user-friendly, web-based data entry, data quality control, data monitoring, preparation of reports for the Data and Safety Monitoring Board (DSMB) and analyses, data lock, data cleaning, and preparing datasets for submission to an NINDS data repository; 
     
  • The DCC will provide support for web-based communication and access to study-wide information (e.g., protocol amendments), as well as for a public website for each trial to promote outreach and recruitment.

Network trials:

Project proposals from industry and academic investigators are submitted in response to separate announcements, and are selected for funding through the standard NINDS process as outlined in the related announcements.

The network trials utilize a variety of the NIH agreement mechanisms (e.g., Cooperative Research and Development Agreements [CRADAs]) that maximize industry participation and support.

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. Patient representatives and patient advocacy groups must be included in the protocol development process and in review of manuals of operation as well as organizational and oversight committees.

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 Data Coordinating Center' Scope of Work includes, but is not limited to:

1)  Data Management

  • Creating and/or network DCC Standard Operating Procedures (SOPs) including, but not limited to all aspects of data management;
  • Finalizing scope of work documents in collaboration with the CCC that clearly delineate CCC and DCC tasks, respectively, and document communication plan (after review, but prior to award, see below);
  • Identifying an experienced data management team that is expected to include an experienced programmer and project manager.

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

  • Reviewing the protocol synopsis and creating the scope of work and timelines for database building, so that the investigators have material for their application; 
  • Working with investigators on statistical design as needed with the help of the DCC statistician, or working with project specific statisticians, when applicable.

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

  • Working with the project lead team of investigators to finalize data management aspects of the protocol; 
  • Working with investigators and CCC to create a database for each trial in a timely manner; 
  • Developing Case Report Forms (CRFs); 
  • Finalizing randomization scheme/process;  
  • Developing a data quality assurance plan;
  • Developing a data monitoring plan.

During the Implementation Phase of approved network projects, the DCC is responsible for:

  • Supporting all data management aspects of trials implementation including but not limited to: 
  • Building on existing hardware and software infrastructure and experience, DCC will be establishing a web-based, user-friendly database for each trial;
  • Incorporating security features consistent with the guidelines of the U.S. DHHS, including but not limited to secure, password protected database access, and audit trails for database changes;
  • Implementing procedures for backing up the program’s clinical and administrative data, including intermittent duplication of the database with storage at a remote facility; 
  • Protecting patient confidentiality at all steps in the submission and analysis of clinical trials data and ensuring the technical integrity and security of the data management systems; 
  • Providing in a timely manner data and reports at the request of the DSMB, the FDA, or the NINDS;
  • Providing in a timely manner true copies of data files and supporting documentation for all network-supported protocols;
  • Supporting web-based or other mode of central randomization;
  • Providing documentation of drug distribution, in collaboration with the CCC;
  • Establishing quality assurance procedures for data quality and completeness;
  • Answering database questions and resolving technical issues for database users.
  • Providing efficient project management for data management projects;
  • Promoting standardization of data collection across trials, including using the NINDS Common Data Elements (CDE), when available, or helping develop common data elements by working with NINDS on submitting data elements and meta-information for use in the CDE initiative.  (see http://www.commondataelements.ninds.nih.gov for more details);
  • Working with the CCC to report and track trial status in terms of enrollment and retention;
  • Transferring data to statistician and others for interim analysis as needed, and at the end of follow-up, cleaning and closing-out the database.

2)  Data Quality Assurance

  • Overseeing data quality control, including but not limited to regular data queries and data monitoring and cleaning to assure data completeness and quality.

3)  Data Sharing

  • Supporting and promoting data sharing after trial completion by preparing a final, limited personal health information or de-identified data set in a format appropriate for data sharing, for submission to a secure data repository after publication of the primary study results or after 18 months, whichever comes first.

4)  Communication

  • Working with the CCC and Clinical Sites to support study communication, including, but not limited to an investigator communication platform/website where the study documents, the protocol and amendments, the manual of procedures, and the other study communications are stored;
  • Providing staff training in database use and answering questions regarding database use;
  • Working with the CCC to ensure that the trial status and results are posted on clinicaltrials.gov, as required; 
  • Working with the CCC, clinical sites, and network project teams, to create a public website as platform for recruitment and outreach efforts for all network projects. 

5)  Monitoring

  • Identifying an experienced clinical monitor to conduct at least annual site visits to monitor the quality of record keeping, source documentation and the accuracy of data entry.

6)  Statistical Support

  • Identifying at least one experienced statistician, with a documented track record in successfully designing and implementing clinical trials: expertise in Phase 2 trials is required, and expertise in efficient trial designs, master protocols, and trials in small populations is preferred; 
  • Providing statistical input to potential network project applicants at the request of NINDS in the conceptual, pre-submission phase;
  • Providing statistical expertise to the trial design in the planning and protocol development phase;
  • Providing statistical oversight throughout the trial implementation phase;
  • Providing interim and final analyses per protocol;
  • Supporting analyses and procedures relevant to adaptive and Bayesian designs where applicable
  • Collaborating with the clinical investigators in the preparation of presentations of primary and secondary publications;
  • Providing additional analyses at the request of the DSMB, the FDA, or the NINDS;
  • For network trial applicants who already have an established and successful working relationship with a statistician in the field of the application, the NINDS may allow for his/her participation; this project-specific statistician will have to be willing to work closely with the DCC team and DCC lead statistician in a collaborative manner and under a pre-specified statistical leadership plan.

7)  Collaborating with Other Network Components

  • The DCC PD/PI will be a member of the Steering Committee (SC) and will be serving as DCC member on network lead protocol development working groups.  The network SC is the main governing body of the network, and works with the NINDS to oversee the implementation of all network protocols. The DCC PD/PI and team will be working with PIs of potential new projects during the conceptual phase, and with PIs of network projects selected for funding during the protocol development and planning phase. The DCC PD/PI and team will be working with the project specific SC during the implementation and analysis/publication phase.  The DCC PD/PI will be responsible for data quality.
  • The DCC will be working closely with the CCC in a collaborative and interactive manner. The DCC and CCC – once selected for potential funding – will submit to the NINDS jointly their respective SOPs, revised from the version originally submitted with their applications, based on their jointly developed collaboration plan. They will also submit a scope of work document detailing the division of tasks and responsibilities within their proposed budget.  Before the award is made, the NINDS will review for approval the joint SOP and scope of work documents.  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 DCC and CCC) be delineated.  It is 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.

New for this funding cycle, the network will organize and maintain a Gene Therapy Consortium (GTC), under the leadership of the CCC. Gene therapy trials, either based on projects completing studies through the Ultra-Rare Gene-Based Therapy (URGeNT) program or proceeding directly to clinical trial phase, will also be selected for funding through the process outlined in the related announcements. The URGenT network supports Investigational New Drug (IND)-enabling studies and planning activities for First-in-Human (FIH) clinical testing of gene-based or -directed therapeutics, such as oligonucleotides and viral-based gene therapies, for ultra-rare neurological or neuromuscular disorders.The goal is to accelerate the development of a promising clinical candidate with robust biological rationale and demonstrated proof of concept (POC) data for the intended approach in a model system relevant to a specified patient population towards an IND filing and the initiation of a clinical trial. The NeuroNEXT GTC will conduct clinical trials as the next step in development. Access to the GTC will not be limited to assets developed through the URGeNT network and applicants could enter the development pipeline directly at the clinical trial stage.

The GTC will consist of 6-10 members with expertise in gene-based and gene-targeted therapies, ultra-rare and rare diseases, and clinical trial planning and execution, with particular emphasis on first-in-human or first-in-disease trials, small clinical trials, and adaptive trial design.

The DCC will be responsible for data management, data quality assurance, data sharing, communication, monitoring, and statistical support for the GTC.

Also new for this funding cycle, the CCC and DCC will organize, with the collaboration of network sites, network-linked open conferences to facilitate stakeholder discussions to identify areas of high unmet need and priority. At least one conference annually, in person if possible and virtual if necessary, will be organized focused on different disease or subspecialty areas for each iteration. The goal will be to proactively identify areas in which projects could be proposed to NINDS for implementation in the network. Participation will include at the minimum the members of the NEC and the members of the specific subspecialty interest group, representatives for the interest area from each site, unless already covered through NEC or interest group membership, key opinion leaders from outside the network, and other stakeholders as relevant to the subject area.

NeuroNEXT network structure and management:

The overall structure of the network includes the CCC, DCC, and 25 geographically distributed sites. The CCC will oversee the GTC, which will be activated as needed for gene therapy trials of variable scale.

  • NINDS will be responsible for organizing and providing overall support for the network. The NINDS Division of Clinical Research staff and the NINDS Grants Management Branch 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 recipients as NINDS partner, consistent with the Cooperative Agreement mechanism. The NINDS has appointed an External Oversight Board (EOB). The EOB is an external group of experts who will review the network Program and advise the network investigators and the NINDS. The CCC will be responsible for the oversight of the EOB.
  • 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 yearly by in-person meetings, unless prevented by uncontrolled circumstances.
  • 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;
    • Pediatric studies
  • The DCC will support protocol development and implementation with regards to statistical design, data management, data quality assurance, and analysis, as described above.
  • 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.
  • The CCC will provide overall clinical coordination. See companion FOA for more details describing the responsibilities of the network CCC.
  • 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.

Gene therapy studies in rare disorders:

The GTC will work in collaboration with the CCC, DCC, clinical trial PI, and relevant sites as described above for NeuroNEXT trials. It is expected that only a small number of sites, or in some cases a single site, will be involved in some of the trials, due to the nature of the patient population and intervention. The sites involved in the gene therapy trial may be NeuroNEXT sites or external sites depending on individual project needs.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed
New

New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Funds Available and Anticipated Number of Awards

NINDS intends to commit up to $1.3 Million FY 2023 to fund 1 award.

Award Budget

The expected direct cost for individual awards is up to $1,300,000 per project year.

Award Project Period

This is a one time solicitation to fund a DCC for 5 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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)

Local 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)

Federal Government

  • 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
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed. 

Required Registrations

Applicant Organizations

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

  • System for Award Management (SAM)– 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.
    • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
  • eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission. 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 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.

Eligible Individuals (Program Director/Principal Investigator)

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

  • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
  • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
  • An application that has substantial overlap with another application pending appeal of initial peer review (see 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Only one DCC application per institution (normally identified by having a unique UEI number or NIH IPF number) is allowed. However, applicants may apply for an award for the CCC 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 DCC and a Clinical Site may be made to the same institution.

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

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

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

Letter of Intent

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

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

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

The letter of intent should be sent to:

Joan Ohayon
Telephone: 301-496-9135
Email: ohayonj@ninds.nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

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.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

The applicants should outline prior experience in managing multicenter trial infrastructures and the planning and execution of multicenter clinical trials in the personal statement and relevant publications portion of their bio-sketch. The applicants should outline their experience and expertise in study design and data analysis in multicenter clinical trials, as well as any experience and expertise in small clinical trials and gene and gene-targeted therapeutic trials.

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide must be followed. The additional instructions also apply:

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

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

  • Conceptual activities;
  • Planning activities;
  • Start-up activities;
  • Randomization support;
  • Implementation activities;
  • Close-out phase activities;
  • Participation in investigator meetings, SC and other leadership committee functions;
  • Site monitoring;
  • Communication, documentation and reporting;
  • Support of study drug management; 
  • Support of the GTC and network-linked conferences

The PD/PI must be available to attend all network investigator meetings, which may include conference calls twice a month and in-person meetings.

The total should not exceed $1.3 Million direct costs per year in years 1-5 (all of which will be 12-month project years).  The release of funds will be milestone-driven, according to milestones 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).

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Leadership 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 Data Coordinating Center PD/PI and staff, and how the data management and statistical team will be directed.

Collaboration and Communications 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 describe their ability to work in a collaborative and interactive manner with the Clinical Sites, the Clinical Coordinating Center, and NINDS and its partners in all aspects of the network program. Applicants should describe their communications plan with the CCC and Clinical Sites within the network. Applicants are encouraged to describe any special expertise or unique strengths they can offer to the collaborative effort (e.g., established database tools, hardware, software, quality control tools, monitoring expertise, team leadership and training, communications platforms, website design and management).

Data Management, Quality Assurance and Monitoring Plan:

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

  • Collect data in a user-friendly manner, with a user interface directed at the experience and knowledge of users (rather than that of programmers, data managers or statisticians);
  • Collect data in a manner appropriate to the source of data (i.e., data collected by people should be entered by people, data generated by machines should be imported from the machine, data generated in a lab should be entered by the lab, etc.);
  • Integrate data from disparate sources seamlessly;
  • Validate data as thoroughly as possible on collection and/or entry;
  • Validate data completely, on an ongoing basis;
  • Have a rigorous error and query resolution process, which monitors data quality throughout the collection process;
  • Allow for the easy dissemination of data to statisticians and other analysts, in a variety of formats;
  • Allow for the easy production of regular reports on trial status and progress;
  • Have graduated, role-based security, which permits varying degrees of access to data based on an individual’s role in the study;
  • Protect any personal health information (PHI) collected from unauthorized access, and create a log of all authorized access;
  • Assemble all study data in a well-documented central store, to facilitate data sharing and dissemination.

Statistical Support Plan:

Based on the outline above, the PD/PI should describe in the Approach section of the Research Strategy, how all statistical aspects of trials from the pre-application conceptual phase, the planning phase, the implementation phase and the analysis and publication phase will be supported.  It is anticipated that the DCC will provide full statistical support for all network projects. However, the PD/PI should briefly describe how in the alternative scenario of a non-DCC statistician this statistician would be integrated in network DCC operations of their project. Under the alternative scenario, the project statistician leads the statistical design, analysis plans, and the final analysis for publication, remaining blinded during the course of the trial.  The DCC statistician leads the data management and preparation of unblinded reports and analyses. In the Conceptual and Planning phases, both statisticians will work together to ensure the design is suitable for implementation through the network. The applicant should outline their expertise in exploratory clinical trials and adaptive designs. 

In addition, the PD/PI should describe their experience and expertise in statistical aspects of rare diseases and/or gene therapy and gene-targeted therapy trials, and expertise in small clinical trials. The DCC will be supporting clinical trials conducted by the gene therapy consortium.

Data Sharing:

According to the goals and tasks outlined above, the PD/PI should describe in the Approach section of the Research Strategy section how standardization of protocols, data collection and data collection instruments will be promoted, including the integration of NINDS common data elements, if applicable. The PD/PI should describe how datasets of completed trials will be submitted for data sharing to the NINDS repository, using data exchange standards.

Trial Start-up and Participant Recruitment:

Participation in the network will be a complex and time-consuming undertaking.  Therefore, in the Research Strategy under Preliminary Data/Approach section, the applicant should include a description of current and up to five of the most recently completed trials that were coordinated by the DCC, along with a detailed record indicating the following, in a table format:

  • The start-up time for each trial in terms of establishing a database and other tools (including CRFs, randomization mechanism)
  • Time from last patient last visit to database lock
  • Time from database lock to final primary analysis

In addition, the application should include the following information:

  • A description of data management system/software the applicant uses currently or proposes to use for this network should be provided in the Resources/Facilities section of the application.
  • A description of data sharing procedures.
  • Published manuscripts that highlight recently coordinated trials should be referenced in the application in the biosketch or in the literature cited section of the application.
  • Data supporting expertise relevant to the design and execution of trials in rare and ultra rare neurological conditions.

Project Management and Coordination Plan:

The application should include, in the Research Strategy section, the SOPs, with key documents (e.g., Conflict of Interest policy) used by the DCC in the implementation of multi-center clinical trials, included, but not limited to SOPs describing database access, data quality control, data queries with audit trails, etc. 

Transition plan: The application should include plans for continuing the trials already funded and underway in the network, without significant disruption. The application should also include transition plans for the end of the award period, should the DCC not be selected for funding in the next funding cycle.

Letters of support (LOS): the application should list the LOS providers, and the LOS from senior intitutional officials demonstrating a clear commitment to support the DCC and/or the PD/PI (e.g., additional protected time, departmental research leadership position, facilities, space, or resources) , industry collaborators, other stakeholders, should be included LOS section.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The following modifications also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
  • Generally, Resource Sharing Plans are expected, but they are not applicable for this FOA
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined 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.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form

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

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential fieldof the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

 

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 in the Resources/Facilities section, the resources that could be available to support the proposed network DCC, commenting particularly on those aspects that will enhance their programmatic and scientific efficiency.  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 (included in the Letters of Support section of the application) from either the GCRC/CTSA Program Director or PI.  Having a GCRC or CTSA at the institution is not a requirement for application.

Post Submission Materials

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.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.  Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact

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

Scored Review Criteria

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those 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?

  • Do the investigators have a track record of working collaboratively? 
  • Do the investigators have a track record in successfully designing and implementing the statistical and data management aspects of multicenter clinical trials?
  • Do the investigators have a track record of supporting trials in rare diseases and/or gene or gene-targeted therapy 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? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed 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, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Are the plans for data collection and analysis adequate? In particular, are the plans for managing study start-up conducive to efficiency and reducing delays?

Are the plans for collaboration with other parts of the network and external partners, particularly industry partners, clear and feasible?

Are the transition plans clear and adequate?

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 such as additional protected time, departmental research leadership position, facilities, space, or resources and by providing departmental and institutional support letters? 

Additional Review Criteria

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

  • Do the investigators provide consistent evidence for collaborative leadership in statistical and data coordination of multicenter trials, and is there evidence of experience in and willingness to participate appropriately in a collaborative program as described in this FOA?
  • Does the investigator have a successful track record in trial statistical and data coordination?
  • Are interactions/communications between the DCC and the CCC, clinical sites and the community clearly described and creatively optimized?
  • Are the investigators likely to carry-out the key tasks in a timely manner, including, but not limited to establishing the database, data cleaning, analysis, and data sharing?

Protections for Human Subjects

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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 individuals of all ages (including children and older adults) 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.

Vertebrate Animals

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.

Biohazards

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

Resubmissions

Not applicable

Renewals

Not applicable

Revisions

Not applicable

Additional Review Considerations

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

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the 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).

Authentication of Key Biological and/or Chemical Resources:

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.

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by an appropriate Scientific Review Group convened by NINDS Scientific Review Branch, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

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.

Applications will be assigned to NINDS. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the NINDS Advisory Council. 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.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

Section VI. Award Administration Information

1. Award Notices

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

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

Recipients 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 terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75 and 2 CFR 200, 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 recipients 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below. 

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

  • Coordinating all aspects of data collection and management for network research protocols, including reporting to the NINDS, CCC, DSMB, and clinicaltrials.gov.  
  • Recipients 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 DCC. 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. 
  • An agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. 

Areas of Joint Responsibility include:

  • A SC composed of three Clinical Site 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. Steering Committee will appoint a SC Chair.  
  • The DCC 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. Recipients 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 recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients 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.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 and 2 CFR Part 200– Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and 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)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

Joan Ohayon, RN, MSN, CRNP, MSCN
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9135
Email:ohayonj@ninds.nih.gov

Peer Review Contact(s)

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Email: nindsreview.nih.gov@mail.nih.gov

Financial/Grants Management Contact(s)

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
Email: ChiefGrantsManagementOfficer@ninds.nih.gov

Section VIII. Other Information

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

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.

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