Required Application Instructions

It is critical that applicants follow the 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

This funding opportunity announcement (FOA) intends to provide clinical investigators and their support teams in an Institutional Development Awards Program (IDeA) academic research setting the necessary professional development, infrastructure and capacity building to conduct pediatric clinical trials research for children with a variety of conditions. The IDeA States Pediatric Clinical Trials Network (ISPCTN) is being developed to foster study of any diseases and conditions relevant to the pediatric population, but priority will be given to the four focus areas of the Environmental influences on Child Health Outcomes (ECHO) Program (RFA-OD-16-004) which include: 1) upper and lower airway disease; 2) obesity; 3) pre-, peri-, and postnatal outcomes; and 4) neurodevelopment.

The goal of the ISPCTN is to provide access for underserved and rural populations to state-of-the-art clinical trials and transfer of findings that will benefit the health of all children. This will be accomplished by supporting professional development in clinical research of faculty-level pediatricians and their support teams (Research Nurse Coordinators, Data Managers) and by engaging them in clinical trials. 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. These awards will ultimately result in a well-qualified national network of pediatrician scientists who will help strengthen the research capacity to meet the need for highly skilled physician investigators who can take advantage of new technologies and respond to the increasing demands for high quality pediatric clinical trials.

Rigorous use of appropriate scientific methodology, deployed across the ISPCTN, in conjunction with collaborative efforts, will achieve the numbers of patients required to provide answers more rapidly than individual sites acting alone. The ISPCTN will primarily function to augment pediatric clinical trials initiated by other entities to improve access to relevant populations, accelerate overall study accrual, and support advances in pediatric clinical research. Studies initiated within the Network will also be encouraged. Each selected IDeA location will support a local team of a physician-investigator, a Research Nurse Coordinator, and a Data Manager. The ISPCTN will be directed by a Steering Committee with standing committees and subcommittees. A Scientific Oversight Board and a Data and Safety Monitoring Board (DSMB) will be constituted as well.

The NIH Project Scientists, one from the NICHD and one from the NIGMS, will assist the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) of the Clinical Sites and the Data Coordinating and Operations Center (DCOC) of the ISPCTN, in identifying research topics of high priority for the implementation of pediatric protocols appropriate to the Network goals and objectives.

Protocol development and implementation will be coordinated by the DCOC. The DCOC will provide needed instruction on all aspects of the research initiatives. The DCOC will also administer capitation and implementation costs for pediatric clinical trials, as needed. Competition for a DCOC to support the Network is solicited under a companion FOA (RFA-OD-16-002).

The IDeA Program was authorized by Congress for the purpose of broadening the geographic distribution of NIH funding for biomedical and behavioral research by enhancing the competitiveness for research funding of institutions located in states in which the aggregate success rate for grant applications to the NIH has historically been low. Disparate funding distributions may stem in part from having relatively few competitively supported biomedical and behavioral investigators in IDeA States.

This Funding Opportunity will establish a pediatric research network among eligible institutions in the 23 states and Puerto Rico that are currently participating in the IDeA Program that will be capable of conducting pediatric clinical trials, particularly in rural and underserved areas. Supported by a DCOC that will provide capacity building and professional development in all aspects of clinical trials research and facilitate the operations of the Network, this funding opportunity will establish and maintain the infrastructure necessary to conduct state-of-the-art pediatric research in these institutions.

In order to respond to the need for access to state-of-the-art clinical research for historically underrepresented populations, to enhance pediatric clinical trial capacity at a national level, and to implement well-designed clinical trials in pediatric populations, the NIH will establish the ISPCTN. The ISPCTN is being developed as a separate, but related program to the Environmental influences on Child Health Outcomes (ECHO) Program. The ECHO Program intends to investigate the longitudinal impact of pre-, peri-, and postnatal environmental exposures on pediatric health outcomes with high public health impact. The ISPCTN will enable clinical trials to be conducted using the reach of participating ISPCTN institutions to engage participants in underserved and rural areas. The ISPCTN will be designed to study any diseases and conditions relevant to the pediatric population, but priority will be given to the four focus areas of the ECHO Program which include: 1) upper and lower airway disease; 2) obesity; 3) pre-, peri-, and postnatal outcomes; and 4) neurodevelopment.

The overall framework of the ISPCTN will consist of dedicated pediatric clinical trial teams at participating institutions, a professional development component, and a central Data Coordinating and Operations Center to provide comprehensive services across the Network. This ISPCTN could partner with academic institutions outside the IDeA consortium to augment geographic diversity of their clinical trials. This enhanced research capacity would provide a portal of entry to populations historically not included in multisite pediatric studies, particularly rural and underserved communities.

Site-Dedicated Research Staff

Trained pediatric clinical trial teams at IDeA institutions that are able to implement studies independent of the disease or condition under study would provide quality and consistency in data collection. In addition to a pediatric scientist-investigator, each participating location would support a pediatric-trained Research Nurse Coordinator and a Data Manager. The research staff would be capable of implementing almost any study protocol, with the occasional exception of a specialized procedure or assessment not available or feasible at their particular location.

Professional Development

A mentoring and professional development component would leverage existing activities within the IDeA program, augmented by pediatric-specific clinical trial resources. The professional development program will contribute to maintaining quality, currency, and sustainability of the Network.

Data Coordinating and Operations Center (DCOC)

The DCOC will support the ISPCTN by providing data coordination functions for pediatric clinical trials. In addition, the DCOC will benefit the IDeA consortium by providing technical instruction, adherence to state-of-the-art data standards, quality assurance, and an operational interface between the IDeA program and other entities that wish to partner with the Network to expand the reach of their pediatric clinical trial enrollment.

Interface with other entities

The ability to collaborate with other funded investigators to increase their enrollment, provide greater opportunity and diversity in study participation, and accelerate study completion can be advantageous to the IDeA sites by providing exposure and partnerships with experienced investigators. Similarly, the IDeA sites can benefit other entities by providing professional study implementation with access to relevant populations and with no additional overhead costs; capitation fees, protocol training, data collection services and infrastructure will be provided by the DCOC. The partnering capacity of an IDeA-based pediatric research network would allow participation in research founded on scientific opportunity and public health needs.

Interested researchers would contact the ISPCTN DCOC as a clearing house to determine feasibility and Network interest. Clinical trials to be conducted through the Network would require approval by the ISPCTN Steering Committee in conjunction with the NIH Program Official. This availability would be limited to NIH-funded studies that have undergone NIH peer review to assure scientific quality. Although trials addressing any disease or condition relevant to the pediatric population will be considered, priority will be given to proposed pediatric trials on one of the four focus areas of the Environmental influences on Child Health Outcomes (ECHO) Program: (1) upper and lower airway conditions; (2) obesity; (3) pre-, peri-, and postnatal outcomes; and (4) neurodevelopment. The DCOC would provide capitation fees per patient per protocol while partner programs would provide protocol specific training through the DCOC. Incentives for partners to engage the ISPCTN include no additional costs for recruitment because capitation fees, protocol training support, data collection services and infrastructure are provided by the DCOC, plus access to additional participants including access to generally underrepresented populations. The NIH encourages all proposed programs to foster the participation of individuals from racial and ethnic groups underrepresented in biomedical and behavioral research, individuals from disadvantaged backgrounds, individuals with disabilities, and women.

Other engagement opportunities would include consultation and input from the ISPCTN members on study design and implementation, especially in rural areas. The Network could also provide both scientists and patient families to serve on regional community engagement advisory committees. This consultative process would allow investigators to receive input at an early stage of study development and provide greater assurance of relevance and feasibility prior to formal engagement of the Network for data collection.

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

Higher Education Institutions

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

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

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• 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) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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

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

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 assess the program, attend Steering Committee Meetings, and submit all documents, data, and reports as required.

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

Applicant organizations may submit only one application.

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).

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the "Apply for Grant Electronically" button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

A letter of intent to apply is not required. Although it 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 to best plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent from the appropriate, high-ranking institutional official(s) from the lead institution 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:

Robert Tamburro, MD, MSc
Telephone: 301-480-2619
robert.tamburro@nih.gov

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: Describe the research infrastructure and facilities that are available and accessible to this program. This includes the existence of funded laboratories and research space and activities that will meet and sustain the needs of the program. As appropriate and applicable, describe any existing resources supported by the IDeA Program that are leveraged and utilized.

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

Biographical Sketch: The biographical sketch should reflect the strengths, leadership, and administrative skills, and scientific expertise of the PD(s)/PI(s). The 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 (2.4 person months for each year of the four year award). The PD(s)/PI(s) must be an investigator with previous training and scientific expertise in pediatrics who has some prior clinical research experience. 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. Any publications that resulted from participation in those studies should be listed. His/her 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.

The biographical sketch of the Research Nurse Coordinator 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.

A Data Manager should be available to provide data compilation and analysis. This individual will be expected to work closely with the DCOC. The Data Manager must be trained in data compilation and analysis, and will work with the DCOC in ensuring local data collection quality, protocol specific training, and transmitting data in a timely manner.

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 to offset the time and effort allotted for PD(s)/PI(s) commitment to the Network (2.4 person months for each of the four years of the award). It is expected that the PD(s)/PI(s) will to make a substantial, long-term commitment of effort to Network responsibilities.
• Salary and fringe benefits may be requested for the Research Nurse Coordinator, who may also assist in recruiting efforts, for up to 12 person months.
• Salary for a part-time Data Manager with responsibilities directly associated with the ISPCTN program may be requested, for up to 2.4 person months in the first year for professional development, with increased support up to 6 person months in the ensuing years.
• Travel to Steering Committee Meetings. The PD(s)/PI(s), Research Nurse Coordinator, and Data Manager are expected to attend Steering Committee Meetings for the IDeA States Pediatric Clinical Trials Network. These Meetings allow research results to be shared across the Network and with PDs/PIs who have engaged the Network to conduct their studies; and ongoing instruction in protocol implementation as needed. Funds should be requested in the budget for this purpose.
• 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.

Capitation fees and study implementation costs will be provided by the Data Coordinating and Operations Center for the Network.

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 primary investigator beyond those expenses directly attributable to Network projects;
• Travel of the PD(s)/PI(s), Research Nurse Coordinator, or Data Manager to scientific meetings other than the Steering Committee Meetings;
• 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.

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.

Research Strategy:

In addition to the sections specified in the instructions in the SF424 (R&R) Application Guide, provide the following sections:

Program Administration

• Describe the strategy and administrative plans to be used to oversee and monitor the program/team.
• 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 are expected to be Good Clinical Practice (GCP) certified. GCP training is available free of charge at https://gcp.nihtraining.com/ and at https://gcplearningcenter.niaid.nih.gov/Pages/default.aspx. The DCOC will maintain centralized records on training and other activities on ISPCTN staff at all locations. Such certification will be mandated as part of the award.

Proposed Implementation of Program

• Provide an overview of the proposed program: Describe the immediate and long-term objectives of the program, including activities that will be used to implement the pediatric clinical trials research development, and how outreach efforts to recruit pediatric participants for funded clinical trials would be conducted. A description of the program's access to a diverse, rural or underserved subject population should be included.
• The description should include how the pediatric clinical trials team will coordinate with their home institutions and faculty, as well as potentially partner with other pediatrics-focused entities in other IDeA States within their region.
• The description should also include how they will collaborate with other institutions, organizations, and networks outside of the IDeA Program.

The Clinical Site will be expected to participate in clinical trials no later than the beginning of the second year of the award.

Program Evaluation

• Describe an evaluation plan to review and determine the effectiveness of the program in your home institution on an annual basis. This should include plans to obtain feedback from institutional officials at the home institution and any other IDeA-eligible institutions with which you have partnered, and the clinical trial PDs/PIs, to help identify weaknesses and to provide suggestions for program improvements.
• Specified evaluation metrics should be tied to the goals of the program, such as success in recruiting and retaining clinical trial participants.

Letters of Support: Include letters of support from participating parties. The application must include a statement from the applicant institution (senior institutional official) describing the commitment to the planned program.

The institution must assure that protected time will be allowed for the PD(s)/PI(s) (2.4 person months for each year of the four year award), Research Nurse Coordinator (up to 12 person months for each year of the four year award), and Data Manager (up to 2.4 person months for year one, 6 person months for years 2-4) selected for the program.

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 total costs requested for any one year, should address a Data Sharing Plan in conjunction with the Data Coordinating and Operations Center. Data sharing plans are expected to have a local component to provide data to a central resource and the Data Coordinating and Operations Center is expected to assume responsibility for the central resource.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

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 Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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 NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

The IDeA States Pediatric Clinical Trials Network is aimed at developing research teams in entities / institutions located in IDeA States who are able to participate in pediatric clinical trials in conjunction with the Data Coordinating and Operations Center (DCOC) to recruit and retain children from underserved or rural areas, and implement those clinical trials within IDeA sites. 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? 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 PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Does the PD(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? Does the research team at the center 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 (provided by the DCOC), recruitment and conduct of clinical trials, data management, 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? Is there evidence of innovative ideas for conducting quality pediatric clinical trials research in a traditionally research underrepresented state using available funding?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

Does the application effectively describe how the research team will function together and within their institution to conduct research? Is there an effective evaluation plan to review and determine the effectiveness of the program? Does the applicant have 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 centers, the DCOC and the NIH in a manner summarized in this FOA?

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 children, 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?

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 diverse, rural or underserved subject population? Are there additional administrative strengths, such as affiliations with other research units or organizations that strengthen the environment of the applicant Clinical Site?

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

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

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

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

Not Applicable

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

Not Applicable

Not Applicable

Not Applicable

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

Not Applicable

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

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

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 Scientific Review Branch at the NICHD, 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 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 appropriate national Advisory Council or Board. 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.

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.

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.

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 Steering Committee, the DCOC, the NICHD, and the NIGMS.
• Representing the site on the ISPCTN Subcommittee of the overall 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 Scientists. 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, 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 NIH IC, an ISPCTN Clinical Site Investigator, or the DCOC. If the regulatory sponsorship responsibility is assigned to a NIH IC, NIH Project Scientists/Medical Monitors will obtain, through the ISPCTN DCOC, 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.

• Provide technical assistance and participate as voting members of the Steering Committee.
• 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 NICHD Program Official, 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 Committee.
• Participate on the Steering Committee and all active subcommittees.
• Collaborate with the NICHD Program Official in recommending administrative actions to enhance scientific productivity.

NIH Program Official

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

• Carry out continuous review activities with the NICHD/NIGMS Project Scientists 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, DSMB, Scientific Oversight Board, 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

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. A member of the NICHD Grants Management Branch 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 NICHD, and supported by the DCOC, and report to the NICHD Director.

Logistics of both conference calls and Steering Committee meetings are the responsibility of the DCOC. The Steering Committee, with the assistance of the DCOC, is responsible for coordinating protocol development, descriptive study design, protocol submission, study conduct, quality control and study monitoring, trial 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 and the NIH that govern its operations, including publications. These policies and procedures can be amended by the Steering Committee and the NICHD/NIGMS. All ISPCTN members will be required to accept and implement all policies, common protocols and procedures approved by the Steering Committee.

Scientific Oversight Board

The Scientific Oversight Board assists and reports to the Steering Committee in the identification and prioritization of topics for pediatric clinical research. The members of the Scientific Oversight Board are independent from the DCOC and Clinical Sites. The Scientific Oversight Board will be determined by the NIH Scientific Officers, in conjunction with the Program Official, and consists of individuals with expertise in clinical trials, biostatistics, epidemiology, and pediatric clinical research. Additional members with specific scientific expertise may be appointed. Parents of children in IDeA states can and should be highly encouraged to serve on the Scientific Oversight Board.

Data and Safety Monitoring Board (DSMB)

For ISPCTN studies, an independent DSMB will be established to monitor and provide recommendations to the NICHD Director regarding participant recruitment/enrollment, safety, data quality, and other issues, as appropriate. The DSMB will also review the Steering Committee-approved common protocol, informed consent templates, milestones, and monitoring plans prior to the start of recruitment. It is recommended that, if possible, a single central IRB is used 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. A Dispute Resolution Panel composed of three members will be convened. 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 progress report, 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.

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)

Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)

Telephone: 301-710-0267

There must be a contact for all participating ICs.

Robert Tamburro, M.D., MSc
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-480-2619
Email: robert.tamburro@nih.gov

Regine Douthard, M.D., MPH
National Institute of General Medical Sciences (NIGMS)
Telephone: 301-435-1759
Email: douthardr@mail.nih.gov

Sherry Dupere, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-496-1485
Email: duperes@mail.nih.gov

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

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.