Department of Health and Human Services
Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)


 Office of the Director

Components of Participating Organizations

National Institute of Allergy and Infectious Diseases (NIAID)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Drug Abuse (NIDA)
National Institute of General Medical Sciences (NIGMS)
National Institute of Neurological Disorders and Stroke (NINDS)

All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers.  The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Behavioral and Social Sciences Research (OBSSR)

Funding Opportunity Title

Data Coordinating and Operations Center for the ECHO IDeA States Pediatric Clinical Trials Network - 2 (U24 Clinical Trial Required - Infrastructure)

Activity Code

 U24 Resource-Related Research Projects – Cooperative Agreements

Announcement Type

Reissue of RFA-OD-16-002

Related Notices
  • August 23, 2019 - Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-137.
  • July 26, 2019 - Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-128.
Funding Opportunity Announcement (FOA) Number

RFA-OD-19-025

Companion Funding Opportunity

RFA-OD-19-026,  UG1 Clinical Research Cooperative Agreements - Single Project

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

93.310, 93.855, 93.865, 93.279, 93.859, 93.853 

Funding Opportunity Purpose

 This funding opportunity announcement (FOA), issued by the Office of the Director (OD), National Institutes of Health (NIH), invites applications from entities/institutions in Institutional Development Award (IDeA)-eligible States to participate as the Data Coordination and Operations Center (DCOC) in the Environmental Influences on Child Health Outcomes (ECHO) IDeA States Pediatric Clinical Trials Network (ISPCTN). The DCOC will support the Clinical Sites of the ISPCTN to conduct multicenter clinical trials research, assuring the participation of children living in rural or underserved communities located in IDeA states, and build pediatric research capacity for IDeA states to support the conduct of clinical trials of relevance to rural or underserved children in IDeA states. The DCOC and the Clinical Sites, together, will form the ISPCTN.    The ISPCTN is the intervention part of the ECHO program and supports its overall mission: to enhance the health of children for generations to come. The award will support clinical trial pediatric research in the 5 focus areas of the ECHO program: pre-, peri-, and postnatal outcomes; obesity; upper and lower airways; neurodevelopment; and positive health.

Key Dates
Posted Date

August 30, 2019

Open Date (Earliest Submission Date)

November 2, 2019

Letter of Intent Due Date(s)

November 2, 2019

Application Due Date(s)

December 2, 2019, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

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

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

February 2020

Advisory Council Review

May 2020

Earliest Start Date

 August 2020

Expiration Date

December 3, 2019

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow 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 the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.


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

    Section I. Funding Opportunity Description
    Section II. Award Information
    Section III. Eligibility Information
    Section IV. Application and Submission Information
    Section V. Application Review Information
    Section VI. Award Administration Information
    Section VII. Agency Contacts
    Section VIII. Other Information

    Part 2. Full Text of Announcement
    Section I. Funding Opportunity Description
    Purpose

    The purpose of this funding opportunity announcement (FOA), issued by the Office of the Director (OD), National Institutes of Health (NIH), is to invite applications from entities/institutions in Institutional Development Award (IDeA)-eligible States to participate in the Environmental Influences on Child Health Outcomes (ECHO) IDeA States Pediatric Clinical Trials Network (ISPCTN) as the Data Coordination and Operations Center (DCOC).   The DCOC will support the Clinical Sites of the ISPCTN to:

    --Conduct multicenter clinical trials research, assuring the participation of children living in rural or underserved communities located in Institutional Development Award (IDeA) states.  

    --Build pediatric research capacity for IDeA states to support the conduct of clinical trials of relevance to rural or underserved children in IDeA states.

    The ECHO ISPCTN is the intervention part of the ECHO program and supports its overall mission: to enhance the health of children for generations to come.   Through the rigorous use of appropriate scientific methodology and by recruiting and retaining the numbers of participants that justify multicenter trials, the ISPCTN aims to provide answers to relevant research questions more robustly and rapidly than any one site could do alone. The Network will be primarily responsible for initiating studies, although the Network may also collaborate with other NIH research networks. 

    This RFA will request applications for the DCOC and a companion FOA (RFA-OD-19-026) will solicit applications for the Clinical Sites of the ISPCTN.   

    Background

    Congress authorized the IDeA Program in 1993 to broaden the geographic distribution of NIH funding for biomedical and behavioral research. The program aims to enhance the competitiveness for research funding of institutions located in 23 states and the Commonwealth of Puerto Rico in which the aggregate success rate for grant applications to NIH has historically been low.   Hence, the NIH designed this program to serve the health research needs of the rural or underserved populations in these states and to increase and strengthen research teams to compete successfully for NIH funding. 

    In 2016, the NIH established the IDeA States Pediatric Clinical Trials Network (ISPCTN) to provide access to state-of-the-art clinical trials for communities living in IDeA states.  The NIH aimed to leverage the resources that it had developed in these states in clinical and translational research through the IDeA Program and bridge a gap by providing these communities access to clinical trials to improve health. 

    The ECHO ISPCTN is the only NIH pediatric clinical trials network with a specific focus on rural or underserved populations, populations of great prevalence in IDeA states. Children living in rural communities experience worse health outcomes compared with children living in urban and suburban areas.  These health inequities result from poor socio-economic conditions, limited access to health care, fewer adults with postsecondary education, greater number of uninsured populations, and a lack of social support in rural areas.

    Children in IDeA states have been under-represented in clinical trials, and access to state-of-the-art clinical trials will help to answer important questions that will result in health benefits for this population.  The ISPCTN is uniquely positioned to identify targeted solutions to address the health issues of rural or underserved children by conducting clinical trials and disseminating the findings that will improve the health of children.  Through this approach, the ISPCTN will help bridge an important gap in pediatric health research.

    This FOA builds on the success of the first cycle of the ISPCTN (RFA OD 16-001 and -002) which developed infrastructure and pediatric clinical trials expertise in IDeA states and assured the participation of rural or underserved children in the ISPCTN clinical trials.  The Data Coordinating and Operations Center and the Clinical Sites, together, will form the ISPCTN, a research network to conduct pediatric multicenter clinical trials as part of the ECHO program.

    Network structure

    The overall framework of the ISPCTN will consist of dedicated pediatric clinical trial teams at participating IDeA states Clinical Sites and a central Data Coordinating and Operations Center (DCOC) to provide comprehensive support of the Network. 

    Data Coordination and Operations Center (DCOC): The DCOC will support and collaborative leadership for the network’s research projects.

    Examples of services the DCOC will provide include:

    • input to development of salient research questions and clinical trial protocol study designs,
    • sample size calculations and statistical advice,
    • developing protocol data management system and procedures,
    • developing data collection forms and protocol tools,
    • performing data analyses,
    • administering scientific protocol funds for sites with ECHO Program Office approval,
    • submitting protocols to a single institutional review board, 
    • coordinating and providing logistical support for the activities and meetings [e.g. the Steering Committee, Leadership Committee, Protocol Review Committee (PRC), Data and Safety Monitoring Board (DSMB)],
    • overall study coordination and quality assurance,
    • facilitate training and professional development of Clinical Sites.

    Clinical sites: Each selected ISPCTN Clinical Site will support a team of a Senior Investigator, a Senior Faculty Development Leader, one or two Junior Faculty, and a Research Nurse Coordinator.

    Partner institutions: To enhance research expertise and potential to build capacity, DCOC applicants may propose collaboration with other institutions.  Applicants may collaborate with other IDeA States institutions in their own state or other IDeA states.  Applicants are encouraged to propose collaboration with an IDeA Program-Infrastructure for Clinical and Translational Research (IDeA-CTR) awardee (https://www.nigms.nih.gov/Research/DRCB/IDeA/Pages/IDeA-CTR.aspx) or a Clinical and Translational Science Award program (see www.ctsaweb.org) in their own state or in another IDeA state.  Applicants may consider collaboration with other ECHO components or investigators (https://www.nih.gov/research-training/environmental-influences-child-health-outcomes-echo-program ).  The NIH will award a minimum of 60% of total costs to institutions within IDeA states.

    Governance and Oversight: ISPCTN governance will include a Leadership Committee, Steering Committee, working groups, and subgroups, as needed. The ECHO Program Office will convene an independent Protocol Review Committee (PRC) and an independent Data and Safety Monitoring Board (DSMB) for the Network.   The ISPCTN will develop and participate in a single IRB that will streamline IRB approval while maintaining patient safety and human subjects’ oversight.

    Clinical Trials:  The network will complete and report a minimum of 3 multicenter clinical trials during this funding period.  Each multicenter clinical trial should be focused on one or more of the 5 focus areas of the ECHO program, and among all three multicenter trials, at least 2 of the 5 focus areas should be represented.  The 5 focus areas of the ECHO program are pre-, peri-, and postnatal outcomes; obesity; upper and lower airways; neurodevelopment; and positive health. The DCOC and the NIH will closely monitor participant accrual and retention.

    Research Topics: The award will support pediatric clinical trial research in the 5 focus areas of the ECHO program.  Examples of potential research topics include, but are not limited to:

    • To what extent does a smoking cessation intervention during pregnancy among recalcitrant smokers result in improved infant and child respiratory outcomes?
    • To what extent can screening and early referral services improve neurodevelopmental outcomes for rural children? 
    • Do mobile technology-based health interventions (mHealth) among obese children--designed to overcome rural health care access challenges—result in sustained weight reduction?
    • To what extent do interventions to improve parenting improve child well-being?

    The Steering Committee and NIH project scientist will identify research topics of high priority research protocols aligned with Network goals and objectives.

    Research infrastructure enhancement: The DCOC will enhance its own research infrastructure by adding needed equipment and office space to conduct ISPCTN protocols.   Additionally, the DCOC may add any additional staff (beyond those required in this FOA) as needed to conduct capacity building and ISPCTN protocols, as budget allows.

    Program Administration: All proposed clinical research activities must employ applicable standards that are consistent with those adopted by the Department of Health and Human Services for use in U.S. health care and public health operations.  All ISPCTN staff involved in clinical research projects must be, at a minimum, Good Clinical Practice (GCP) certified. GCP training is available free of charge at https://gcp.nihtraining.com/ and at https://learningcenter.niaid.nih.gov/. The DCOC will maintain centralized records on training.

    Professional skills development: The network will focus on capacity building of professional skills among Senior faculty, Junior Faculty, and Research Coordinators to help improve their skills in clinical trials development and implementation.   The DCOC will work with a Senior Faculty Development Leader at each Clinical Site (or a partnering site) to help to guide this educational component and to implement clinical research skills development plans.   Professional development will include senior faculty level-led educational opportunities, including didactic and interactive training in developing appropriate research questions, matching study design and implementation to the question, multicenter clinical trial protocol development and implementation. Professional development will be provided by the DCOC, the Clinical Site, or either in partnership with another research institute.

    Junior faculty pilot proposals: One junior faculty at each institution, during the second year of the funding cycle, will complete a single research proposal (1 project per Clinical Site) for a pilot study that the ISPCTN may conduct at one or more Clinical Sites. A second Junior Faculty at the same institution may collaborate with the first Junior Faculty to develop the pilot study proposal.  Junior faculty should propose a pilot study that provides needed information to inform a future multicenter clinical trial. Junior faculty are encouraged to develop the proposal with the input of Senior research faculty at the Clinical Site and/or Senior research faculty at a collaborating site, if appropriate.   The ISPCTN Steering Committee will consider all pilot proposals and will select about five for implementation during the remainder of the funding cycle.

    Ongoing studies in the ECHO ISPCTN

    Vitamin D Supplementation in Children With Obesity-Related Asthma (VDORA1) (NCT03686150)

    https://clinicaltrials.gov/ct2/show/NCT03686150?term=IDeA+states+Pediatric+Clinical+Trials+network&rank=1

    Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care (PTN_POPS) (NCT01431326) https://clinicaltrials.gov/ct2/show/NCT01431326?term=POP01&rank=2.  This study is a collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Pediatric Trials Network.

    Objectives and Scope

    The DCOC will work collaboratively with the Clinical Sites and the ECHO Program Office.  Examples of services the DCOC will provide the ISCPTN include:

    Network Logistics and Communications

    • Provide in-person meeting and conference call support for the Steering Committee, Leadership Committee, Protocol Review Committee (PRC), and Data and Safety Monitoring Board (DSMB);
    • Provide support to Network priorities as determined by Leadership Committee and Steering Committee
    • Provide regular updates and reports to the ECHO Program Office;
    • Establish an account with clinicaltrials.gov and maintain listings for all ISPCTN studies;
    • Establish and implement a Comprehensive Communications Plan for the ISPCTN that includes:

           -ensuring that a public website remains current and includes an adequate description of studies (e.g., protocol, publications, contact information);

           -ensuring that a website for network investigators remains current and includes study specific information, including regulatory documents, study protocols, manuals of operations, and standard operating procedures;

           -ensuring bidirectional communication with stakeholders, participants, and their families.

    • Serve as an ISPCTN liaison for any related ECHO Program activities; the DCOC PD/PI will represent the ISPCTN as a member of the overall ECHO Cohorts Steering Committee;
    • Function as a point of contact for other entities to interface with the ISPCTN to engage ISPCTN sites for collaborations with other networks or investigators.

    Clinical Trials Skills Development Core

    • DCOC will create a Clinical Trial Skills Development Core with the goals of enhancing knowledge and assuring performance of Clinical Site investigators and staff. 
    • Examples of core protocol development skills include:  articulating a clinical trial research question based on health impact for children and a research gap analysis, justification for multi-center network to meet study objectives, rationale for experimental design, including event rates for primary outcome, participant eligibility, and analysis
    • Examples of clinical trial skills in protocol implementation include feasibility assessment, such as participant availability, risks to participation, participant recruitment, assessment of participant burden, and participant retention.
    • Examples of best practices for study conduct include standard operating procedures, quality assurance and quality control plans in multicenter clinical research, delineation of milestones that are performance-based to achieve completion of the trial on time and on budget, and contingency plans to proactively confront potential delays or disturbances in meeting milestones.
    • Conduct ongoing evaluation of the effectiveness of the Clinical Trial Skills Development Core and engage in continuous quality improvement of the program.

    Clinical Study/Trial Development

    Provide expert assistance in protocol development/design, analysis plans, and feasibility assessment. This includes assistance with study design, epidemiology, and biostatistical expertise for sample size estimates and analysis, as well as protocol document creation (informed consent/assent forms, Manuals of Operations, data collection forms, and training guides) and processing.  Assistance should include helping Clinical Site Investigators develop proposals that include background\rationale including gaps in the literature that the trial will fill, a specific and actionable research question with clear primary comparisons, a main hypothesis, a clear impact on child health of the anticipated results, projected number (per group) and characteristics of the participants, a well described intervention, the primary outcome and any salient secondary outcomes, the overall analytic strategy, a study timeline, a well described budget, and why the trial is particularly applicable to the ISPCTN. Proposed methods should directly support the research question. 

    Clinical Study/Trial Operations

    • Provide resource allocation to conduct clinical trials, including maintenance of a funding pool to provide capitation fees to local sites for network studies;
    • Provide project management expertise, including timelines, and site monitoring for protocol implementation at the Clinical Sites;
    • Provide standard operating procedures for clinical research data collection, processing, completeness and quality assessments, management, analysis, security, storage, and sharing;
    • Implement well-documented, high quality site monitoring, Quality Assurance/Quality Control plans; 
    • Provide recruitment and retention monitoring and reporting to the Clinical Sites, Steering Committee and Leadership Committee;
    • Implement a Single Institutional Review Board (IRB);
    • Outline and implement study recruitment plans for identifying, screening and enrolling subjects;
    • Establish processes for tracking studies and changes/approvals by the Protocol Review Committee, Data and Safety Monitoring Board (DSMB) and single Institutional Review Board (IRB);
    • Document and follow procedures for handling protocol deviations/violations;
    • Comply with NIH policy, all regulations applicable to research, and law;
    • Provide ISPCTN study staff (DCOC and clinical sites) with pertinent ongoing training including documentation of proficiency (protocol training and certification, Human Subjects Protection Training, Ethics Training, IT Security, data capture, etc.), and Good Clinical Practice (GCP) training. Maintain centralized records on certification of ISPCTN staff at all locations;
    • Provide detailed training for Steering Committee and NIH approved protocol implementation at Clinical Sites to Clinical Site Investigators, Research Coordinators, Study Staff, and clinical staff involved in research protocols.
    • Support human subjects data and biospecimen repository and regulatory activities;
    • Establish a process for preparing and managing IND/IDE reports and other requirements.  Be prepared to become the IND or IDE holder of record as deemed appropriate by the NIH Program Official; and
    • Develop a well-defined reporting process for adverse event (AE) and unanticipated problems (as defined by OHRP) that is defined precisely and is in compliance with local IRB requirements, 21 CFR 312.32 for Investigational New Drugs (IND), 21 CRF 812.150 for Investigational Device Exemptions (IDE), and International Conference on Harmonisation Regulations E2A, as applicable.
    • Implement a plan to report safety analyses and report AEs to the Data and Safety Monitoring Board (DSMB) in a format that highlights trends or signals.

    Dissemination of Findings

    • Establish, document, and follow processes for manuscripts and presentations tracking, preparation, review, communication and submission. Provide support to Clinical Sites to report results through publications in peer-reviewed journals; 
    • Create reports and summaries for the DSMB, Steering Committee, Leadership Committee, and NIH;
    • Report results to ClinicalTrials.gov and prepare and provide to appropriate data repositories public and restricted use data sets in accordance with NIH data sharing and access policies; and
    • Develop Network-wide plans to return results to participants when appropriate and to share with participants the overall results and contributions of each study.

    Pilot project development for Junior Faculty

    DCOC will provide

    • a review and recommendation process and administer an opportunity fund to implement about 5 single or multisite pilot projects developed by junior faculty at clinical sites and  
    • guidance to junior faculty who seek opportunity funds at each site.

    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
    Renewal

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

    Clinical Trial?

    Required: Only accepting applications that propose clinical trial(s))

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

    NIH intends to fund 1 award, corresponding to a total of up to $8,000,000, for fiscal year 2020.

    Award Budget

    An applicant for the DCOC may request a budget for up to $1,750,000 per year in direct costs plus $3,500,000 per year in direct costs for capitation fees for distribution to the Clinical Sites, and for necessary monitoring, DSMB visits, and Protocol Review Committee activities.

    Award Project Period

     The project period cannot exceed five 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)

    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

     Only institutions or organizations in the following IDeA states/commonwealths are eligible to respond to this FOA:

    Alaska, Arkansas, Delaware, Hawaii, Idaho, Kansas, Kentucky, Louisiana, Maine, Mississippi, Montana, Nebraska, Nevada, New Hampshire, New Mexico, North Dakota, Oklahoma, Puerto Rico, Rhode Island, South Carolina, South Dakota, Vermont, West Virginia, Wyoming.

    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.

    • 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)– 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 to register in eRA Commons.  Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 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.

    Eligible Individuals (Program Director/Principal Investigator)

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

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

       To be eligible for an award through this announcement, any Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) from an IDeA eligible state with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with his/her organization to develop and submit an application for support.  The primary institution must be in an IDeA state.  Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

    The PD(s)/PI(s) for the DCOC must have appropriate expertise and capability in biostatistics, data management, informatics, data analysis and project management, and strong skills and experience in the design, execution and analysis of pediatric research.  Applicants are encouraged to include expertise in pediatric multi-center clinical research.

    For single PD/PI applications, the PD/PI will be designated as the DCOC Director. For multi-PDs/PIs applications, the DCOC Director designation will be the Contact PD/PI.

    At a minimum, the DCOC PD(s)/PI(s) and staff must be prepared to cooperate effectively in all Network functions with the NIH and the Clinical Sites. The PD(s)/PI(s) must have prior experience operating a data coordinating center in multicenter studies in the previous five years. Together, the DCOC PD/PI and staff should have the following minimum qualifications in terms of experience and expertise in:

    • planning, developing and executing pediatric studies, and the special consent and IRB procedures needed for the conduct of research in children, is strongly preferred.
    • a broad range of clinical trial study design and statistical expertise including pragmatic clinical trial methodology.
    • designing data collection systems including distributed data entry, and capabilities and experience with research performance and data quality control systems.
    • project management and knowledge of workflow and research team practices in implementation of clinical trials.
    • oversight and analysis of several studies concurrently.
    • distributing scientific protocol funds to the Clinical Sites, and accounting for such funds with regular reporting to the NIH ECHO Program Officer and Project Scientist.
    • working with a variety of stakeholders including research participants and families, practitioners, researchers, hospital/clinic and research informatics and technical personnel, and research organizations on workflows and practices of health care systems.
    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.  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 NOT-OD-11-101).
    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 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:

    Maribeth Champoux, PhD
    National Institutes of Health, Center for Scientific Review
    Telephone: 301-594-3163
    Email: champoum@mail.nih.gov

    Page Limitations

    All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed. For this specific FOA, the Research Strategy section is limited to 30 pages.

    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.

    Facilities and Other Resources:

    Applicants should describe facilities and other resources that may be relevant to ISPCTN research. This can include state-of-the-art data management systems, which may be shared or may be available to develop and expand the scientific productivity of the ISPCTN.

    SF424(R&R) Senior/Key Person Profile

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

    Biographical Sketch: The biographical sketch of the PD(s)/PI(s) should reflect the strengths, leadership, administrative skills, and scientific expertise The applicant must demonstrate staff experience and expertise in biostatistics, data management, data analysis, data quality assurance and project management in multicenter research.

    PD(s)/PI(s) must demonstrate prior experience in the design, conduct, data collection, analysis and management of major collaborative multicenter clinical trials research projects, preferably in pediatric clinical research, and provide evidence of successful performance as a DCOC for multicenter studies within the past five years. Further, the applicants need to show evidence of monitoring of trials, including the ability to generate monthly reports of enrollment and follow up for the ISPCTN Clinical Sites, safety reports for the DSMB, and provision of support of data files. Contributions in key areas of research development and design, data collection and analysis, monitoring of trial progress, and track record of publications that resulted from participating in the studies should be described and related to the proposed DCOC structure and function.

    Previous experience in pediatric clinical research studies and Food and Drug Administration Investigational New Drug/Device protocols is preferred. Knowledge of Federal patient privacy and data confidentiality requirements and appropriate experience in ensuring that relevant mechanisms and procedures are in place must be provided in the application.

    In addition, special administrative strengths or experience, as well as participation in administrative aspects of clinical research (IRB, DSMB, Advisory Board for clinical research, clinical research committees, and so forth) for the PD(s)/PI(s) and additional staff members should be highlighted. The level and support of clinical trials can be described.

    If the PD(s)/PI(s) has substantial experience with or staff expertise in, research involving vulnerable populations, special sensitivity to the issues of informed consent in the critically ill, research under emergency circumstances, or experience in multicenter research in children, it should be summarized here.

    R&R Budget

    All instructions in the SF424 (R&R) Application Guide must be followed.  The PD(s)/PI(s) should submit Base Budget estimates for all years including:

    • PD(s)/PI(s) or collectively if MPD/MPI must commit no less than 50% (6 person months) effort. Applications with differing leadership effort commitment plans should document in detail how that would support Network needs.
    • Participant and protocol costs.
    • Participant and protocol training costs for studies and trials will be supported for distribution to the Clinical Sites.
    • Support for required monitoring Protocol Review Committee activities, DSMB meetings, ISPCTN Steering Committee meetings, and ISPCTN Leadership Committee meetings.

    Items that may NOT be supported with funds from this FOA include:

    • Direct support of the laboratories, salaries, fringe benefits, travel, and research projects of the established investigators serving as primary investigator beyond those expenses directly attributable to Network projects;
    • Salary and support for central institutional administrative personnel (e.g. budget officers, grant assistants, and building maintenance personnel), which are usually paid from institutional overhead charges unless the conditions in Sec. 8.1.1.6 of the NIH Grants Policy Statement are met;
    • Salary and support for administrative activities such as institutional public relations or health and educational services.
    R&R Subaward Budget

    All instructions in the SF424 (R&R) Application Guide must be followed.   Partnerships are encouraged to strengthen any aspect of DCOC performance.  All partnerships must be well-justified.  If partnerships with institutions outside of IDeA states are proposed, a minimum of 60% of total costs must be awarded to institutions within IDeA states.

    PHS 398 Cover Page Supplement

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

    PHS 398 Research Plan

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

    Research Strategy:

    In addition to the sections in the SF424 (R&R) Application Guide, complete the following

    If this is a renewal, describe participation and contribution to the ISPCTN in detail including contributions in key areas of research development and design, patient recruitment and retention efforts, and data collection and analysis.  In Biosketch, describe publications, presentations at major scientific meetings, workshops, and seminars resulting from ISPCTN activities. 

    New applicants must describe their recent experience and participation in multi-center randomized clinical trials. Applicants must describe their specific roles in each trial (coordinating center, principal investigator, participating site, steering committee, writing committee, trial design and development, etc…). In Biosketch, list 4 relevant publications, presentations at major scientific meetings, workshops, and seminars resulting from participation in studies.  

    Staffing Plan

    The DCOC PD(s)/PI(s) will provide input on study design, data collection, data analysis, and publication of ISPCTN studies. The PD(s)/PI(s) will actively participate during all phases of a research study. The application should describe plans for staffing DCOC functions from protocol design through analysis. The DCOC should have some degree of flexibility in staffing to be able to respond to changing needs and variation in work effort of the ISPCTN. For instance, meeting deadlines, trial startup and completion, and other variables occur which necessitate increases and decreases in staff effort from the DCOC. The applicant should describe staffing plans for day-to-day functioning of the Network and management of Clinical Site per participant and protocol costs.

    Professional Development Plan

    The applicant should describe plans to provide general professional development opportunities to Network DCOC and Clinical Site personnel.  These plans should include development and implementation of protocol specific training to ensure consistency and quality in data collection in pediatric clinical trials.

    The applicant should propose a structure and content for a Clinical Trial Skills Development Core to enhance knowledge and assure performance of Clinical Site Investigators and staff on core protocol development skills including (but not limited to):

    • articulating a clinical trial research question based on health impact for children and a research gap analysis;
    • justification for multi-center network to meet study objectives;
    • rationale for experimental design;
    • identifying appropriate outcomes and endpoints;
    • designing an intervention;
    • identifying the population of interest and participant eligibility criteria (inclusion and exclusion)
    • assessing the feasibility of a proposed trial;
    • additional clinical trial design elements including sample size determination, blinding, randomization, stopping rules and interim analyses;
    • ensuring fidelity of the intervention, including participant availability, risks to participation, location of recruitment, assessment of participant burden;
    • best practices for study conduct, including standard operating procedures, quality assurance and quality control plans in multicenter clinical research, delineation of milestones that are performance-based to achieve completion of the trial on time and on budget, and contingency plans to proactively confront potential delays or disturbances in meeting milestones;
    • analysis approaches and concerns;
    • ethical considerations;
    • recruitment and retention techniques, including recruitment and retention monitoring;

    The Clinical Trial Skills Development Core should also facilitate standardization of the training and provide clinical research career development opportunities for investigators across the network.  Professional development will include senior faculty level-led educational opportunities, including didactic and interactive training in multicenter clinical trial protocol development and implementation provided by the DCOC, the site institution, or in partnership with another research institute. The DCOC will develop a curriculum adapted to the needs of the research team at clinical sites. The DCOC should include direct professional development opportunities for both junior and senior level faculty at the Clinical Sites to facilitate improvement in study design and protocol creation skills. The DCOC should conduct ongoing evaluation of the effectiveness of the Clinical Trial Skills Development Core and engage in continuous quality improvement of the program.

    Logistical and Other Support Services

    Applicants must describe plans for logistical and support services relevant to the ISPCTN, including for in-person: Steering Committee meetings (three to four per year) and conference calls, Leadership Committee meetings (as many as two per year), Protocol Review Committee meetings, DSMB meetings, webinars and other meetings as needed by the ISPCTN.  This should include

    documentation in the form of minutes and actions resulting from the above-mentioned meetings,  handling travel arrangements for Protocol Review Committee members, DSMB members, and selected consultants as needed, and as resources permit. The applicant should describe how the DCOC will provide infrastructure and support for ongoing communication of the ISPCTN via email and teleconference. Plans for logistical and support services should reflect expertise in coordinating sample storage and study drug/equipment assignment. Describe plans to oversee the patient and protocol funds for the studies and trials and maintain subcontracts with the Clinical Sites for disbursement. The DCOC will prepare a quarterly report of protocol fund distributions and outstanding invoices for the NIH and ISPCTN Steering Committee.

    Clinical Trial Protocol development and implementation plan

    The applicant should provide a plan for how clinical trials will be developed, implemented, and monitored in collaboration with the Clinical Sites of the ISPCTN.  This includes how the DCOC will assist protocol development with respect to design of manual of procedures, data collection forms, data collection systems, electronic technology, and data entry systems. Applicants should provide evidence of data management and program support capabilities by describing their standard operating procedures to include data collection, management, analysis and quality control. A system to ensure availability of patient randomization for studies outside of normal business hours (i.e. nights, weekends, and holidays) is required. Applicants must include plans for support of electronic mail and communication as well as plans for a web-based system for participants of the ISPCTN. The DCOC must develop and maintain a website for both public access and private, with secure investigator access.

    Applicants for the DCOC must describe plans for protocol training of research staff at the Clinical Sites of the ISPCTN.  Applicants must include plans for training sessions for scientific protocol implementation and for ongoing yearly certifications necessary for ISPCTN studies.

    Applicants for the DCOC must describe plans for organizing and conducting both onsite and offsite monitoring of research studies.  This includes, but is not limited to, generation of data errors and needed edits as queries to sites and assuring that ISPCTN Clinical Sites fully comply with NIH regulatory requirements including Human Subjects Protections, informed consent, reporting of adverse events, human safety and welfare provisions, and FDA requirements as indicated by specific studies. Additionally, overall documentation and coordination of IRB approvals are the responsibility of the DCOC. Applicants must describe plans for oversight of data collection, transfer, and management.

    Reporting

    Applicants must describe plans for generating reports on subject enrollment and retention at least twice per month for multiple concurrent studies for use by the DSMB, and for the Steering Committee and Leadership Committee. The DCOC should describe experience with and an approach to timely documentation and dissemination of meeting minutes. Applicants should describe experience in preparing data and manuscripts for publication, and experience with data sharing. The DCOC PD(s)/PI(s) will report to the NIH and the Steering Committee progress on study timelines and milestones, and quarterly reports of protocol fund distributions.

    Administration and Management

    Described and justify partnerships and collaborations between an eligible organization and an IDeA Awardee.   Memoranda or other formal agreements/commitments should be included in Letters of Support.

    The PD(s)/PI(s) should describe plans for managing and administering the DCOC. The DCOC must estimate the appropriateness and reasonableness of resources needed for individual projects and the ability to manage those resources efficiently during the course of the research. The applicant should demonstrate flexibility among personnel based on effort needed. Prior experience with meeting formal deadlines (e.g., FDA reporting requirements, national meetings, Steering Committee meetings, DSMB meetings, Advisory Board Meetings, and so forth) should be delineated in the application.

    The PD(s)/PI(s) must describe detailed plans for financial administration of the Network.  The ability to efficiently process invoices from ISPCTN Clinical Sites and provide timely distribution of protocol funds is essential. Experience with capitation for study subject recruitment by Clinical Sites is essential. This includes providing and monitoring funds to the Clinical Sites for patient enrollment at regular intervals. Experience with subcontracts is required, as there is occasional need to supplement resources through arrangements with outside organizations based on individual protocol requirements.

    The applicant should propose an operational structure for providing and coordinating all DCOC functions for several Network protocols simultaneously (including lines of responsibility/authority for professional staff) and propose an administrative and management structure that would support and enhance the operational structure.

    Letters of Support: Document with letters of support from appropriate individuals, including the Chief Executive or Operating Official (or equivalent) of the applicant institution, the departmental and institutional commitments to participate in ISPCTN supported research. Evidence of past support can also be cited.

    Describe support in areas of grants management, personnel management, space allocation, data coordination and confidentiality (including electronic data systems, such as hardware, software, maintenance and informatics technology), procurement, and equipment as well as general support of the research, as well as evidence of past research support. Include in the application, letters of support from appropriate leaders of institutional component services.

    There must be a clearly expressed intent to participate in a cooperative manner with other ISPCTN Clinical Sites, the NIH, the Protocol Review Committee and the Data and Safety Monitoring Board in all aspects of research in a manner consistent with the terms of the award. The prioritization of ISPCTN work at the DCOC must be expressly stated in the application. The DCOC should confirm that it will provide logistic and data support for all projects.

    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, with the following modification:

    • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. 

    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

    Only the following fields are required:

                    1.1 Study Title

                    1.2 Is this Study Exempt from Federal Regulations?

                    1.3 Exemption Number (if applicable)

                    1.4 Clinical Trial Questionnaire

                    2.1 Conditions or Focus of Study

                    2.4 Inclusion of Women, Minorities, and Children

                  2.7 Study Timeline

                    3.1 Protection of Human Subjects

                    3.2 Multi-site question and associated single-IRB plan

               3.3 Data and Safety Monitoring Plan

               4.2.a Narrative Study Description

    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 field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

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

    See more tips for avoiding common errors.

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

    In order to expedite review, applicants are requested to notify the peer review contact by email at {champoum@mail.nih.gov} when the application has been submitted. Include the FOA number and title, PD/PI name, and title of the application.

    Pre-Application Workshop

    An informational pre-application workshop via webinar, addressing the scientific and administrative issues associated with this initiative, is anticipated around one month prior to the Letter of Intent due date. The purpose of this webinar workshop is to (1) familiarize the potential applicant with established NIH guidelines and criteria for review, (2) discuss the areas of NIH programmatic emphasis, and (3) facilitate the submission of a well-organized 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.

    A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

    Specific for this FOA:

    The IDeA States Pediatric Clinical Trials Network is aimed at developing research teams in entities / institutions located in IDeA States who are able to work with PDs/PIs of relevant clinical trials and the Data Coordinating and Operations Center (DCOC) to recruit and retain children from rural or underserved areas and implement those clinical trials within IDeA sites.  These teams will augment and strengthen the clinical research capacity of an IDeA-eligible State.

    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

    Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy?  For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

    Does the proposed Center address the needs of the research network that it will coordinate? 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 network?

    Investigator(s)

    Are the PD(s)/PI(s) and other personnel well suited to their roles in the Center? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing multicenter clinical trials research? Do the investigators demonstrate significant experience with coordinating collaborative clinical research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the Center? Does the applicant have experience overseeing selection and management of subawards, if needed?  

    With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

    Specific for this FOA: Are the scientific, administrative, statistical and academic qualifications of the PD(s)/PI(s) and the research team at the DCOC, as well as the qualifications of the PD(s)/PI(s) and applicant institution to participate fully as the DCOC for the ISPCTN demonstrated?

    Do the key personnel possess appropriate and adequate knowledge and experience in areas relevant to the conduct of collaborative clinical research, especially multi-center randomized clinical trials, including experience in research design, execution, data management and quality control, preferably in pediatric clinical research?  

    Are the appropriate commitment, availability, and flexibility of staff and PD(s)/PI(s) time for the satisfactory conduct of the studies and ISPCTN activities demonstrated?

    Are the experience and qualifications of team members who would be responsible for data quality and management activities appropriate?

    Are the appropriate expertise and capability in biostatistics, the special needs of pediatric subjects, institutions and IRBs, study development and support, data analysis, project management, staff site training, and monitoring/quality assurance procedures described?

    Is the evidence of management capability, including assessment of the PD(s)/PI(s)' ability to estimate appropriate and reasonable resources for research studies, to manage research resources efficiently during study execution, and to enhance collaboration among the Clinical Sites of the Network adequate?

    Does the PD(s)/PI(s) possess prior experience in the design, conduct, data analysis, and data management of major collaborative research projects, experience in pediatric research, and successful performance as a data coordinating center in the previous five years?

    Innovation

    Does the application propose novel organizational concepts, management strategies, or instrumentation in coordinating the research 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?   

    Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

    Approach

    Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research network the Center will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the network, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the network is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the network? Are an appropriate plan for work-flow and a well-established timeline proposed?  Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of 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? 

    Does the application adequately address the following, if applicable

    Study Design

    Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

    Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

    Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

    Data Management and Statistical Analysis

    Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

    Specific for this FOA:

    Does the application demonstrate the quality of the applicant's participation as a DCOC (new applicants) in the recent past or ISPCTN protocols during the current grant period (current DCOC)?

    Does the applicant demonstrate the ability to provide appropriate staffing for all DCOC functions, including all clinical trials related functions from protocol design through analysis and reporting of results?

    Does the applicant demonstrate the ability to facilitate professional development for site level activities focusing on capacity building and clinical trials implementation at clinical sites?  Does the applicant demonstrate the ability to create a Clinical Trial Skills Development Core that will enhance the knowledge of investigators and staff at the Clinical Sites about protocol development, implementation, feasibility assessment, and analysis?  Does the applicant demonstrate the ability to conduct ongoing evaluation of the effectiveness of the Clinical Trial Skills Development Core and engage in continuous quality improvement of the program?

    Does the applicant demonstrate the ability to assist in protocol development with respect to design of manual of procedures and data collection systems, as well as operational support for clinical trials (e.g., data management and program support capabilities including data collection, management, analysis and quality control)?

    Is there evidence for adequate quality of procedures for onsite and offsite monitoring capabilities?

    Is the evidence for quality of reporting capabilities in multicenter trials with respect to twice-monthly reports, trial subject enrollment and retention, and DSMB meetings provided?

    Environment

    Will the institutional environment in which the Center will operate contribute to the probability of success in facilitating the research 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?

    If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

    Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

    If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

    Specific for this FOA:

    Is evidence of the ability to administer patient and protocol costs to Clinical Sites, and to budget and administer support for Steering Committee, DSMB, and Protocol Review Committee meetings provided?

    Is the ability to estimate resources needed for individual projects and manage those resources efficiently during the course of research demonstrated?

    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.

        Study Timeline

    Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, IDeA State resources (CTRs, COBRE, INBRE), practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

    Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

    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

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

    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 networks 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(s) convened by the Center for Scientific Review, 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:

    • 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.
    • Will receive a written critique.

    Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

    Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the NIH Council of Councils. 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 grantee’s business official.

    Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

    Any application awarded in response to this FOA will be subject to 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.

    Under clinical trial directions- Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA. 

    ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

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

    Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

    Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE). 

    2. Administrative and National Policy Requirements

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

    Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency.  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. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html.  Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. 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. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

    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 “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 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:

    -Identification of priority areas for research.

    -Development and implementation of the Network protocols.

    -Collection and transmission of data to the DCOC.

    -Analysis of data in conjunction with the DCOC and publication of results of ISPCTN studies.

    -Acceptance of the collaborative nature and the role of the group process as cooperative and participatory.

    -Projecting subject enrollment for specific protocols during a specified time frame.

    -Design and execution of ISPCTN studies, supervision of personnel, interaction with Institutional Review Boards, interaction with the Clinical Site grants management officials, and collaboration and cooperation with the other Clinical Site PD(s)/PI(s), the Leadership Committee, the Steering Committee, the DCOC, and the ECHO program.  

    -Identifying an ISPCTN site representative for the ECHO Program Steering Committee.

    -Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

    -NIH assistance to the ISPCTN operations will be provided by the ISPCTN Program Official and the NIH Project Scientist(s).  NIH staff will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination above and beyond the normal program stewardship role for grants. In various matters related to study approval and oversight, the NIH staff will have final decision authority, as described below.

    -Study Monitoring and Management: (i) The NIH ISPCTN Program Official/Project Scientist, through the ISPCTN DCOC, will monitor compliance with OHRP and NIH requirements for human subject research, accurate protocol implementation and internal quality assurance across all ISPCTN-supported studies. This includes: participating in the development of and approving Data and Safety Monitoring Plans prior to study initiation; determining the need to conduct for-cause clinical site visits, participating in such visits, and approving recommendations for remedial actions. (ii) NIH staff will participate in ISPCTN Study Management Teams to manage the day-to-day implementation of ISPCTN-supported studies.

    -IND/IDE Sponsorship: The ISPCTN NIH Program Official will determine on a case by case basis whether the regulatory sponsor for a clinical trial conducted under IND/IDE will be an ISPCTN Clinical Site Investigator or the DCOC. The ISPCTN DCOC will provide regular reports on serious adverse events and protocol deviations, and will decide on the final disposition of SAE Reports for all IND/IDE studies.

    -Study Termination: The NIH reserves the right to terminate, curtail or suspend an ISPCTN-supported study for any reason, including but not limited to risks to subject safety, occurrence of unforeseen safety or ethical issues, scientific question is no longer relevant or the objectives will not be met, failure to comply with Federal regulations or Terms and Conditions of Award, and reaching a major study endpoint before schedule with persuasive statistical significance.

    -Access to Data: The NIH will have the right of access to all data (raw and analyzed) generated under this cooperative agreement and may periodically review these data.

    NIH Project Scientists

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

    -Provide technical assistance and participate as voting members of the Steering, Leadership Committees, and all active subcommittees. 

    -Assist with the identification of important areas of study.

    -Assist in the development of study protocols.

    -Assist in the development and review of capitation-based budgets, including the identification of study costs and special institutional needs.

    -Assist in the review and evaluation of each stage of the program before subsequent stages are started in conjunction with the Steering Committee and the Leadership Committee, and make recommendations to enhance the scientific quality of the work.

    -Assist in the reporting of results to the community of investigators and health care recipients.

    -Assist in the conduct of the trials and studies, including ongoing review of progress, possible redirection of activities to improve performance and cooperation, and frequent communication with other members of the Steering and Leadership Committees.

    -Recommend administrative actions to enhance scientific productivity.

    NIH Program Official

    An agency program official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. This Program Official role is separate from the Project Scientists', and will include the following:

    -Carry out continuous review activities with the NIH Project Scientist(s) to ensure that objectives are being met and that all regulatory, fiscal, and administrative matters are handled according to NIH guidelines.

    -Have the option to withhold support to a participating institution if technical performance requirements are not met, such as protocol compliance, enrollment targets, or randomization of subjects, in consultation with the Project Scientists.

    -Initiate a decision to modify or terminate a study based on the advice of the DCOC, Steering Committee, Leadership Committee, Protocol Review Committee, DSMB, and/or Project Scientists.

    -Work with staff in the NICHD Grants Management Branch, who will monitor and evaluate the fiscal concerns and administration, including Facilities and Administrative Fees.

    -Perform other duties required for normal program stewardship of awards.

    -Provide final approval prior to initiation for all ISPCTN-supported studies.

    Areas of Joint Responsibility include:

    Steering Committee (SC)

    The Steering Committee will be the main governing body of the ISPCTN and will have the primary responsibility for developing research policies by consensus, vetting studies to be conducted through the Network, supervising the conduct of the studies, and reporting results.

    The Steering Committee will consist of the PD/PIs (one from each awarded Clinical Site), the PD(s)/PI(s) of the DCOC, and the NIH Staff. The ISPCTN Project Scientists will be the only voting NIH staff members of the Steering Committee and will receive one vote each. The PD(s)/PI(s) of each Clinical Site as well as the PD(s)/PI(s) of the DCOC will also receive one vote each. All major scientific decisions will be determined by majority vote of the Steering Committee. NIH Grants Management advises the Steering Committee on funding matters. Subcommittees will be established by the Steering Committee, as deemed appropriate. An outside chairperson, who is not participating as a PD/PI, will be selected by the NIH to serve as chair in creating the agendas and conducting the meetings, and to vote in the case of a tie vote. Data and Safety Monitoring Boards (DSMBs) will be established at the request of the ECHO Program Office, supported by the DCOC, and report to the ECHO Director.

    Logistics of conference calls, Steering Committee meetings, and Leadership Committee meetings are the responsibility of the DCOC. The Steering Committee, with the assistance of the DCOC, is responsible for coordinating protocol development, study design, protocol submission, study conduct, quality control and study monitoring, trial endpoint adjudication, drug ordering, data management, statistical analysis, protocol amendments/status changes, adherence to requirements regarding investigational drug and other product management and compliance with Federally mandated regulations, and protocol and performance reporting. The DCOC will be responsible for direct communication with the Project Scientists.

    The ISPCTN will establish policies and procedures through the DCOC, the Steering Committee, the Leadership Committee, and the NIH that govern its operations, including publications. These policies and procedures can be amended by the Steering Committee and the ECHO Program Office. ISPCTN members must accept and implement policies, common protocols and procedures approved by the Steering Committee.

    External Scientific Board (ESB)

    Five to seven external experts will serve as the External Scientific Board (ESB) and will be selected and appointed by the ECHO Program Director and NIH Director.  The ESB will review and offer input on ECHO ISPCTN structure, function, and studies, both during protocol development and during the analysis of results.  Members of the Board will provide input based on their individual areas of expertise, as needed over the course of the program.  They will assist the NIH regarding processes and substantive issues that arise during the project and will help ensure that the resources to be delivered by the program are as useful as possible for the end users.  External Scientific Board members may be invited to attend some ECHO ISPCTN Steering Committee meetings. 

    Leadership Committee (LC)

    The Leadership Committee is a subgroup of the Steering Committee.  The Leadership Committee will have representatives from the Clinical Sites, PD(s)/PI(s) of the DCOC, and the NIH staff.   The Steering Committee Chair, who is not participating as a PD/PI, will serve as a member of the LC and will receive a single vote.  The NIH staff will receive a single vote, each LC member from a Clinical Site will receive a single vote, and the DCOC will receive a single vote.  

    The Leadership Committee provides executive leadership for the ISPCTN by providing program oversight, formulating strategic and operational decisions with the input of the SC, prioritizing research activities including concept proposals, expanded concept proposals, protocols, and ancillary studies for implementation.  The LC will also review manuscript topic proposals.  The LC will also formulate governance policies for ratification by the SC, develop SC meeting agendas, and assist in the resolution of disputes within the ISPCTN. 

    Protocol Review Committee (PRC)

    The Protocol Review Committee (PRC) is a network scientific oversight committee for the ISPCTN.  The PRC will review proposed protocols that may be performed within the network.  The purpose of the PRC is to assess the scientific merit of each protocol. The PRC is appointed by, and is responsible to, the ECHO Program Office to provide peer review for the protocols developed by network investigators.  All protocols must have been reviewed and approved by the IDeA States Pediatric Clinical Trials Network (ISPCTN) Steering Committee prior to submission to the PRC. The ISPCTN Steering Committee may also choose to submit preliminary concepts to the PRC for critique prior to fully developing the research protocol, but this is not a requirement. The PRC and the Data and Safety Monitoring Board (DSMB) are separate bodies, which may have overlap in membership.

    The membership of the PRC includes a chair, medical experts, scientists, statisticians, and other clinical research or trial experts as described below. Additional experts may be included in the PRC on an ad hoc basis as necessary to evaluate a respective protocol. The NIH PRC Executive Secretary is responsible for scheduling and attending PRC meetings, taking minutes, and assisting the Chair in drafting the report of the PRC recommendations for the ECHO Director’s Office.

    Data and Safety Monitoring Board (DSMB)

    For ISPCTN studies, an independent DSMB will be established to monitor and provide recommendations to the ECHO Director regarding participant recruitment/enrollment, safety, data quality, and other issues, as appropriate. The DSMB will also review Steering Committee-approved protocols, informed consent templates, milestones, and monitoring plans prior to the start of recruitment. The DSMB will share recommendations with the single IRB.   The ISPCTN will use a single IRB to streamline the protocol approval process and to standardize the monitoring of human subjects' protection in the ISPCTN Program.

    Dispute Resolution

    Any disagreements that may arise in scientific or programmatic matters (within the scope of the ISPCTN awards) between award recipients and the NIH may be brought to Dispute Resolution. The ISPCTN will convene a Dispute Resolution Panel composed of three members. The panel members will be a designee of the ISPCTN Steering Committee, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee.  This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

    3. Reporting

    When multiple years are involved, awardees will be required to submit the 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.

    The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

    In accordance with the regulatory requirements provided at 45 CFR 75.113 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 – 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)

     Mary C. Roary, PhD
    Environmental Influences on Child Health Outcomes (ECHO)
    Office of the Director, National Institutes of Health
    Phone  301-443-5706
    ECHO Phone  301-435-5236
    mary.roary@nih.gov

    Peer Review Contact(s)

    Maribeth Champoux, PhD
    National Institutes of Health, Center for Scientific Review
    Telephone: 301-594-3163
    Email: champoum@mail.nih.gov

    Financial/Grants Management Contact(s)

    Bryan S. Clark, MBA
    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
    Telephone: 301-435-6975
    Email: clarkb1@mail.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.

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