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.

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

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 a Clinical Site. The Clinical Sites of the ISPCTN will:

--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 Clinical Sites and a companion FOA (RFA-OD-19-025) will solicit applications for a Data Coordinating and Operations Center (DCOC) to support the activities of the ISPCTN.

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 children and families 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 child 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 than children living in urban and suburban areas. These health inequities are the result of 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 Clinical Sites and the Data Coordinating and Operations Center, together, will form the ISPCTN, a research network to conduct pediatric multicenter clinical trials as part of the ECHO program.

The overall structure 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.

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 at Clinical Sites, to include needed expertise on clinical trial proposals, and to enhance capacity to recruit rural participants into clinical research, applicants are encouraged to propose collaboration with other institutions. Applicants may collaborate with 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.

Data Coordination and Operations Center (DCOC): The DCOC will provide needed support and collaborative leadership for the network’s research projects. The DCOC will administer capitation and implementation costs for pediatric clinical trials conducted by the Network. The DCOC will also facilitate professional development across the Clinical Sites.

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 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 children with obesity--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: Clinical Sites will enhance their research infrastructure by adding needed equipment and office space to conduct ISPCTN protocols. Additionally, Clinical Sites may add any additional staff (beyond those required in this FOA) as needed to conduct 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. A Senior Faculty Development Leader at each Clinical Site (or a partnering site) will work with the Data Coordination and Operations Center to guide this educational component and implement clinical research skills development plans. Professional development will include senior faculty level-led educational opportunities, including didactic and interactive education 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 may be conducted at one or more Clinical Sites within the ISPCTN. A second Junior Faculty at the same Clinical Site 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.

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

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

Higher Education Institutions

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

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

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

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

Applicant Organizations

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.

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.

PD(s)/PI(s) from IDeA states might not have extensive experience with clinical trials or have comparable track records of publications and funding as more experienced investigators. However, the PD(s)/PI(s) must be capable of providing both administrative and scientific leadership to the development and implementation of the proposed program. The PD(s)/PI(s) will be expected to attend all Steering Committee Meetings, and submit all documents, data, and reports as required.

PD(s)/PI(s) for the Clinical Site should be a board-certified Pediatrician. PD(s)/PI(s) will supervise the development and conduct of ISPCTN clinical research at their institution and/or partner Clinical Site

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

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

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).

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.

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.

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: [email protected]

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

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

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

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

Facilities and Other Resources

Infrastructure and Equipment

Describe the infrastructure available for pediatric clinical research

Clinical Capabilities

Describe the inpatient and outpatient clinical services available for pediatric research. Describe laboratory testing, availability of subspecialists, and institutional pharmacy capable of supporting clinical research. The application should describe the site's staffing and experience in clinical research. Describe the potential for night and weekend recruitment.

Populations available for Clinical Studies/Trials

Applicant Clinical Sites must describe their access to community practices that serve a minimum of 30 percent children from rural homes.

Provide the specific pediatric population available for study by the Clinical Site. Include information for the year 2018 in tabular format.

• The number and percent of children (0-18 years) in the catchment area of the applicant Clinical Site that live in a rural area; describe the catchment area, definition used for rurality, and a brief methodology for this calculation.
• The number of births in your Clinical Site’s hospital (or hospitals).
• The number of discharges from your Clinical Site’s hospital (or hospitals) with a diagnosis of asthma who were children or adolescents.
• The number of ambulatory visits in your Clinical Site among children and adolescents with ECHO-relevant outcomes, for example, pre-term birth, asthma, attention-deficit/hyperactivity disorder, autism spectrum disorder, obesity, well-child checks.

Be specific about your methodology, including the number of clinics or institutions included in your estimates if more than one. Report separately for each location, as well as overall.

Experience with Clinical Trials and Clinical Trials Networks

Describe participation and site success in clinical trials networks, including the first cycle of the ISPCTN, if applicable. Provide information on previous multicenter clinical trials in which the Clinical Site has participated in the previous 5 years. Describe time to site activation, time to initial participant enrollment, numbers enrolled, the length of the enrollment period, and retention (to the extent possible) to the end of the trial among those enrolled.

Data System

Describe the availability of computers, information technology, electronic medical/health records, and other electronic data system(s) and how these technologies will be leveraged for clinical research.

Other Support

Applications should include a list of funded clinical research. This includes but is not limited to financial support from NIH, federal and non-federal granting agencies, and institutional support.

Special Strengths

Applicants are encouraged to describe special or unique strengths that may be relevant to ISPCTN research. This can include expertise in Biostatistics, Epidemiology, Study design or other relevant areas. It may also include established partnerships, presence of an institutional CTR or CTSA, or educational tools or expertise which may be available to develop and expand the scientific productivity of the ISPCTN.

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

Biographical Sketch: A biographical sketch should be included for all key personnel. The biographical sketch should reflect the strengths, leadership, and administrative skills, and scientific expertise of the PD(s)/PI(s).

At least one PD(s)/PI(s) must be a fully qualified, Board Certified pediatrician who is able to make a substantial, long-term commitment of effort to Network responsibilities (no less than 1.8-person months for each year of the five-year award). The PD(s)/PI(s) must be an investigator with previous training and scientific expertise in pediatrics who has prior Pediatric Clinical Research experience. PD(s)/PI(s) will supervise the development and conduct of ISPCTN clinical research at their institution and any partner Clinical Site(s).

Any previous experience with clinical trials including specific roles (e.g. PD/PI, participating site, Steering Committee member, writing committee, trial design and development) should be described in the Biosketch. Any publications that resulted from participation in those studies should be listed in this Biosketch. The PD/PI's clinical, academic, administrative, and research time commitments, and availability for ISPCTN research and management activities, should be clearly stated in the Personal Statement of the Biosketch.

One Senior Faculty Development Leader should be designated as a Senior/Key person. The biographical sketch of this senior level faculty should reflect qualifications for guiding clinical trials skills development educational efforts, including teaching clinical trials development and implementation, for other faculty. This faculty member should be able to make a substantial commitment to the Network (a minimum of 0.6 person months for each year of the five year award). Any previous experience in a similar role should be clearly stated in the Personal Statement of the Biosketch. The Senior Faculty Development Leader may be at the primary institution or at a collaborating institution.

One or two Junior faculty should be designated as key persons. These junior faculty need not have extensive clinical trials experience, but they should be willing to build clinical trials development and implementation skills during the funding period with the guidance of senior level faculty at this or other institutions. Junior faculty members identified on the application should be able to make a substantial commitment to the Network (a minimum of 1.8 person months per year for each faculty member included). An institutional commitment of at least 1.8 person months per year for each junior faculty member included should be described in a letter of support.

The biographical sketch of the Research Nurse Coordinator(s) should reflect qualifications through training, background and research experience. It is appropriate to describe the experience, skill set, and accomplishments of individuals who may not have had clinical research experience, but who have the potential to be strong research coordinators. The Research Nurse Coordinator(s) should be able to make a substantial commitment to the Network (no less than a total of 12 person months for each year of the five-year award). Additional part-time research coordinators needed for research may be included in the application.

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

A Base Budget estimate for the Clinical Site should be included for all years. The award provides allowances for each of the following costs:

• Salary and fringe benefits for the time and effort allotted for PD(s)/PI(s) commitment to the Network (No less than 1.8-person months for each of the five years of the award). The PD(s)/PI(s) should make a substantial, long-term commitment of effort to Network responsibilities.
• Salary and fringe benefits for the time and effort allotted for Senior Faculty Development Leader commitment to the Network (No less than 0.6 person months for each of the five years of the award).
• Salary and fringe benefits for the time and effort allotted for one to two Junior Faculty commitment to the Network (approximately 1.8-person months for each Junior Faculty for each of the five years of the award).
• Salary and fringe benefits for the time and effort allotted for the Research Nurse Coordinator(s) (approximately 12 person months for each year of the five years of the award).
• Travel to Steering Committee Meetings and Protocol Meetings. The PD(s)/PI(s), Senior Faculty Development Leader, Research Nurse Coordinator, and at least one Junior Faculty member should plan to attend Steering Committee and/or Protocol Meetings for the IDeA States Pediatric Clinical Trials Network. These Meetings allow research teams to share research results, develop new research protocols, and share experiences with protocol implementation with other site teams across the Network. Steering Committee meetings and/or Protocol Meetings are held in the Washington, DC metro area three to four times per year and will last approximately two days each. The PD/PI or designee, Senior Faculty Development Leader, Research Nurse Coordinator, and at least one Junior Faculty member are required to attend Steering Committee meetings in their entirety. At least one investigator and the Research Nurse Coordinator are required to attend Protocol Meetings. Funds should be requested in the budget for these purposes.
• Administrative support services that are directly associated with and necessary for the Network program, and are not covered by institutional overhead charges, may be requested. Allowable costs include supplies, duplicating equipment, telephone, or maintenance contracts for equipment.
• Consultant costs, equipment, supplies, travel for key persons, and other program-related expenses may be included in the proposed budget. These expenses must be justified as specifically required by the proposed program and must not duplicate items generally available at the applicant institution.
• The Data Coordinating and Operations Center for the Network will provide capitation fees and study implementation costs per protocol that is approved by NIH.

Items that may NOT be supported with award funds include:

• Direct support of the laboratories, salaries, fringe benefits, travel, and research projects of the established investigators serving as PD/PI beyond those expenses directly attributable to Network projects;
• Patient care costs such as inpatient bed days or outpatient visits, except for clinical laboratory analyses essential for trials conducted through the Network;
• 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.

All instructions in the SF424 (R&R) Application Guide must be followed. Partnerships are encouraged to strengthen any aspect of Clinical Site performance, including to enhance research expertise and build capacity at Clinical Sites, to include needed expertise on Clinical Trial proposals, and to enhance capacity to recruit rural participants into clinical research. All partnerships must be well-justified. Recruitment of research participants for clinical trials must take place in IDeA states. 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.

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

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

Specific Aims: All applications should list Specific Aims for the proposed participation in the Network. These should not be the same as the specific aims of the Clinical Trial Proposal (Subsection 5).

Research Strategy:

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

In lieu of a traditional research strategy with the usual headings, the application should use the following subsections: Overall strategy, Readiness for clinical trials, Clinical research skills development plan, Rural engagement plan, and Clinical Trial proposal.

Subsection 1: Overall strategy and administrative plan

The applicant should describe the applicant's overall strategy and administrative plans to oversee and monitor the program/team.

Subsection 2: Readiness for clinical trials

The applicant should describe the institution's readiness to engage in a multicenter clinical trials network, including ability to develop and implement multicenter clinical trials, research infrastructure, and trial recruitment infrastructure.

If this is a renewal, provide a summary of this Clinical Site's accomplishments during the first funding cycle of the ISPCTN. For example, describe improvements to the clinical trials research infrastructure relative to the baseline infrastructure that was in place at the onset of the prior project period; challenges designing or implementing clinical trials encountered during the prior project period and solutions that were successfully implemented; and evidence of overall research productivity attributed to or influenced by the ISPCTN award. In the Biosketch, include and indicate publications, presentations at major scientific meetings, workshops, seminars, and numbers and types of research grant applications submitted and grants/contracts awarded [including funding source] that were attributed to or influenced by the ISPCTN award.

Subsection 3: Clinical research skills development plan

Propose a robust capacity building plan for clinical research skills development of junior faculty, senior faculty, and research coordinators that are included in the grant. The role of the Senior Faculty Development Leader should be clearly stated within the capacity building plan. Knowledge and skills development should focus on clinical research design and implementation. Content knowledge in other areas may be included but must be justified as important to the longer-term development of clinical trial development and expertise at the Clinical Site. For example, applicants may propose epidemiology or biostatistical coursework if needed to improve clinical trial development. Applicants are encouraged to partner with other institutions to provide needed expertise to guide and provide clinical research skills development.

Subsection 4: Rural engagement plan

Propose a strategy to recruit rural participants into one or more ISPCTN trials. Describe the approach to recruiting participants from rural areas, e.g., through engaging rural communities and/or providers. Applicants should describe how they have defined rural areas. Applicants may collaborate with other institutions and entities to allow rural recruitment. Be specific about the role of partner institutions/entities.

Subsection 5: Clinical Trial Proposal

Propose one multicenter clinical research trial that the ISPCTN will conduct during the funding cycle. The trial may be a prevention trial or a treatment trial. The trial should focus on one of the five focus areas of the ECHO program. The clinical trial proposal should include background\rationale including gaps in the literature that the trial will fill, a specific and actionable research question with the primary comparison, the main hypothesis, impact on child health of the anticipated results, projected number (per group) and characteristics of the participants, main elements of the interventions, the primary outcome, the overall analytic strategy, a study timeline, and why the trial is particularly applicable to the ISPCTN. The proposed methods should directly support the research question. The proposal should be feasible within the funding cycle.

Letters of Support: Include letters of support from partnering institutions or outside collaborators with statement of roles/responsibilities. The application must include a statement from the applicant institution (senior institutional official) describing the commitment to the planned program, senior and junior investigators, research staff and infrastructure needed. The institution must assure that protected time will be allowed for the PD(s)/PI(s) (at least 1.8 person months for each year of the five year award), Junior investigators (minimum 1.8 months each for each year), and Research Nurse Coordinator(s) (at least 12 person months for each year of the five year award) selected for the program. The institution of the Senior Faculty Development Leader, whether the primary institution or a collaborating institution, should provide a letter of support that assures that protected time will be allowed for the Senior Faculty Development Leader (minimum of 0.6 person months for each year of the five year award).

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.

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

Section 2 Study Population Characteristics

Inclusion Enrollment Report(s)

The ISPCTN Data Coordination and Operations Center will provide Inclusion Enrollment Reports of Human Subjects for Network protocols and reports to ClinicalTrials.gov for the network.

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.

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

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

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.

This initiative is not subject to intergovernmental review.

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

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

Applications must be 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 Center for Scientific Review Referral Office by email at {[email protected]} when the application has been submitted. Include the FOA number and title, PD/PI name, and title of the application.

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.

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.

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 aims to develop research teams in entities / institutions located in IDeA states to be able to participate in pediatric clinical trials and implement those clinical trials within IDeA sites, including recruiting and retaining children from rural or underserved areas. These teams will augment and strengthen the clinical research capacity of an IDeA-eligible state. PD(s)/PI(s) from IDeA states may not have extensive experience with clinical trials or have comparable track records of publications and funding as more experienced investigators.

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).

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

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

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?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

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:

Does the PD(s)/PI(s) have the scientific, administrative, clinical and academic qualifications to conduct successful clinical pediatric research and to lead the proposed program? Is there evidence that an appropriate level of effort will be devoted by the program leadership to ensure program objectives? Is there evidence that an appropriate level of effort will be devoted by Junior Investigator(s) and the Senior Faculty Development Leader to ensure program objectives? Does the research team at the Clinical Site have the institutional support and capabilities to participate fully in the ISPCTN? Is there sufficient assurance that the required effort of the PD(s)/PI(s) and research team will be devoted directly to professional development in pediatric clinical trials research, recruitment and conduct of clinical trials, and related activities?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

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?

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

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 applicant demonstrate an effective clinical trials skills development plan that is likely to positively impact the research team's ability to design and implement clinical trials in their institution?

Does the applicant demonstrate the ability to successfully implement multicenter clinical trials including the ability to recruit, retain and follow up children in clinical studies?

Is there evidence of a willingness to work and cooperate with other ISPCTN Clinical Sites, the DCOC and the NIH?

Does the research team, with proposed partner institutions or collaborators, have the ability to design multicenter clinical trials?

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?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

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 international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

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:

Does the institution demonstrate the commitment to support pediatric research and the proposed program? Is there evidence of commitment to prioritize ISPCTN studies? Are the research infrastructure and facilities that are available and accessible to this program described? Is there adequate institutional assurance to provide support to the program in areas of fiscal administration, personnel management, space allocation, procurement, planning, and budgeting?

Is there demonstrated adequacy of administrative, clinical, and data organizational management facilities as described in the requirements?

Does the applicant institution have access to a rural or underserved participant population? Does the applicant institution, with or without partner institutions, have the ability to successfully recruit rural participants into clinical trials?

Are there additional administrative strengths, such as affiliations or collaborations with other research units, institutions, or organizations that strengthen the environment of the applicant Clinical Site?

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 international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

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?

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.

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, 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)?

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.

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

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

Not Applicable

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

Not Applicable

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

Not Applicable

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

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

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

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

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:

• 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.
• Geographic distribution of awards

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.

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.

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).

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 NIH 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, 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.

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.

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

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: [email protected] (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: [email protected]

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
[email protected]

Maribeth Champoux, PhD
National Institutes of Health, Center for Scientific Review
Telephone: 301-594-3163
Email: [email protected]

Bryan S. Clark, MBA
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: [email protected]

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

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