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

The purpose of this funding opportunity announcement (FOA) is to invite applications for a centralized Data Coordinating and Operations Center (DCOC) to support the activities of the IDeA States Pediatric Clinical Trials Network (ISPCTN). The funded DCOC will cooperate with the ISPCTN Program Directors/Principal Investigators (PDs/PIs), the NICHD and NIGMS Project Scientists, and the NICHD Program Officer, to identify pediatric clinical trials that are relevant and feasible to implement in the ISPCTN, establish collaborations and partnerships, design or adapt protocols appropriate to generate high quality data, develop and implement quality assurance and quality control measures, establish and maintain human subject protection oversight, comply with applicable policies, regulations, and laws for the research project, and develop and implement relevant professional development programs. The DCOC will have primary responsibility for resource allocation, data management and analysis and data sharing for research conducted through the Network, in collaboration with the ISPCTN Steering Committee and NIH Program Staff. 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 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.

In order to respond to the need for access to state-of-the-art clinical research to 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 in 2016, with funding provided to Clinical Centers in IDeA Program locations and a Data Coordinating and Operations Center, following the competitions announced in RFA-OD-16-001 and RFA-OD-16-002.

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 Institutional Development Award (IDeA) Program supports institutions in 23 states and the Commonwealth of Puerto Rico that historically have not received extensive NIH funding. Within the IDeA Program are several initiatives with a common theme of increasing research capacity and mentoring scientists who can effectively compete for future NIH funding. Many of the IDeA states are primarily rural.

The opportunity for children in rural and medically underserved locations to participate in clinical research studies is limited by time, distance, and logistics. The NICHD proposes to collaborate with the NIGMS to supplement the IDeA Program to address this access gap for these children through a national network for pediatric clinical trials based on establishing a team of highly competent pediatric clinical trial professionals in IDeA states. Providing access to clinical trials in such locations would enable better science and aid in addressing health disparities through recruitment of diverse populations and provide professional development, mentoring and pediatric research opportunities to IDeA state investigators.

The overall framework would 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

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.

Examples of services to be provided by the DCOC include:

• Data collection and storage
• Data processing
• Protocol specific training of research personnel at the individual sites
• Professional development opportunities on topics related to pediatric clinical trials
• Single or Federated Institutional Review Board (IRB)
• Design and conduct of protocols, analysis of data, and reporting of results of Network research.
• Rapid response to inquiries and opportunities for outside research studies based on expertise and capacity
• Interoperable infrastructure to partner with other entities
• Protocol document processing
• Maintenance of Standard Operating Procedures
• Quality assurance
• Compliance with policy, regulation, and law
• Maintenance of a funding pool to provide capitation fees to local sites on a per enrolled patient per protocol basis and to initiate pilot studies.

Interface with other entities

The ability to partner with other studies and other research systems 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. 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.

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.

Objectives and Scope

The functions of the DCOC will include developing protocol data management procedures, devising study designs, providing sample size calculations and statistical advice, developing data collection forms and protocol tools, performing data analyses, administering scientific protocol funds for sites with NICHD approval/concurrence, coordinating and providing logistical support for the activities and meetings of the Steering Committee, DSMB, Scientific Oversight Board, as needed, and overall study coordination and quality assurance.

The DCOC will:

• Provide professional development updates on pediatric clinical research to ISPCTN sites, and protocol specific training on an ongoing basis. 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 certification and other activities of ISPCTN staff at all locations.
• Provide expertise in the design, conduct, data analyses and data management of collaborative clinical trials.
• Function as a point of contact for other entities to interface with the ISPCTN to engage ISPCTN sites for protocols that originate outside the Network. The process will involve establishing liaisons at each active ISPCTN site to rapidly and accurately transfer critical concepts and information to allow each location to assess feasibility for participation.
• Serve as an ISPCTN liaison for any related ECHO Program activities; the DCOC PD/PI will represent the ISPCTN as a member of the overall ECHO Program Steering Committee. In addition, the DCOC PD(s)/PI(s) will be a member of the ISPCTN Subcommittee of the overall ECHO Program Steering Committee.
• Coordinate human subject protection oversight of ISPCTN studies. In alignment with emerging Federal and NIH policy, shared reliance among IRBs to consolidate into a single or Federated IRB will be expected.
• Use informatics and electronic data technologies to design and produce data collection systems; modify and redesign such systems as appropriate for new study protocols. Data collection systems should comply with international standards for interoperability. In anticipation of ISPCTN data to be used to support submissions to regulatory authorities such as the Food and Drug Administration, use of the Clinical Data Interchange Standards Consortium Study Data Tabulation Model and Object Data Model is highly encouraged. For further information see http://www.cdisc.org. When feasible, Common Data Elements as defined by the NIH should be used. For examples and resources, see the NIH Common Data Element Portal at http://www.nlm.nih.gov/cde/. Terms as a basis for defining concepts and forming variables for pediatric topics, particularly adverse events reporting, should use as a default the NICHD Harmonized Pediatric Terminology, which is aligned with the Medical Dictionary for Regulatory Activities (MedDRA). For further details see https://www.nichd.nih.gov/health/clinicalresearch/clinical-researchers/terminology/Pages/current.aspx. Data collected by the ISPCTN is expected to be interoperable and able to integrate with other systems including relevant data repositories for data sharing.
• Provide appropriate and capable leadership and expertise in biostatistics, study design, data management, data analysis and project management. These activities should include, but are not limited to, staff and site professional development and quality assurance procedures. In conjunction with these activities, develop a quality assurance and quality control program to ensure high quality and timely data collection and delivery and maintain data integrity. Standard Operating Procedures for data quality will be posted for public access to maintain transparency.
• Provide research support activities in designing data collection modules, operational procedure manuals, quality control systems, and an internet based communications system for Clinical Site PDs/PIs, Research Coordinators, and other Network staff.
• Manage and distribute patient and protocol funds, after NICHD approval, to participating Clinical Sites on a per protocol capitation basis.
• Establish an account with clinicaltrials.gov and maintain listings for all ISPCTN clinical trials unless exempted by the NICHD Program Officer. Information on establishing an account can be found at https://clinicaltrials.gov/ct2/manage-recs/how-apply. Listings include post completion results posting as per the policies of clinicaltrials.gov and the NIH.
• Provide meeting and conference support for the activities of the Steering Committee, the Scientific Oversight Board and the DSMB through the provision of materials and documentation, meeting planning and logistics, and conference call coordination.
• Organize and conduct multisite monitoring activities in conjunction with the NICHD and NIGMS Project Scientists.
• Provide regular reports to the NIH on enrollment, population diversity, and the allocation of resources. Respond appropriately to changing work needs, Network prioritization and re-prioritization, and changes in staffing.
• Provide administrative and scientific assistance in the preparation of manuscripts for publication of ISPCTN data under the supervision of the NICHD and NIGMS Project Scientists.
• Provide technical expertise and management of novel resources to enhance Network activities. Examples include, but are not limited to, the establishment of semantic interoperability in electronic health records (EHRs) across the Network.
• Prepare and provide to appropriate data repositories public and restricted use data sets in accordance with NIH data sharing and access policies. The ISPCTN data sharing and data access policies will be posted for public access to maintain transparency.
• Establish a process for preparing and managing Investigational New Drugs (IND) and Investigational Device Exemption (IDE) reports and other regulatory requirements. Be prepared to become the IND or IDE holder of record as deemed appropriate by the NIH Program Official. .
• Provide arrangements for data collection and reimbursement of study-related data collection costs at non-Network sites participating in Network studies.
• Support study recruitment by developing community outreach plans including informational material about the opportunities and responsibilities of participating in research and the chance to help others.
• Develop Network-wide plans to return results to participants when appropriate and to share with participants the overall results and contributions of each study.

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

All applicants must either be an eligible organization that is located in an IDeA state or territory, or will partner with an IDeA State organization.

The IDeA eligible states and territories involved are 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, and 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.

Any PD/PI from an IDeA eligible state with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with his/her organization to develop an application for support. Additionally, eligible individuals include PD(s)/PI(s) from non-IDeA states who partner in a multi-PD/PI application with a PD/PI from an IDeA eligible state. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

The PD(s)/PI(s) for the DCOC must have appropriate expertise and capability in biostatistics, data management, informatics, data analysis and project management, and strong skills and experience in the design, execution and analysis of pediatric research.

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

At a minimum, the DCOC PD(s)/PI(s) and staff must be prepared to cooperate effectively in all Network functions with the NIH and the Clinical Sites. The PD(s)/PI(s) and other key personnel must have prior experience operating a data coordinating center in multicenter studies in the previous five years.

Experience in planning, developing and executing pediatric studies, and the special consent and IRB procedures needed for the conduct of research in children, is strongly preferred.

The PD(s)/PI(s) must have the ability to assist in designing protocols, data collection systems including distributed data entry, and capabilities and experience with research performance and data quality control systems.

The PD(s)/PI(s) must have the ability to manage and analyze data for several studies concurrently.

The PD(s)/PI(s) must have the ability to hold and distribute scientific protocol funds to the Clinical Sites, and to maintain accounting for such funds with regular reporting to the NICHD Project Officer and Program Project Scientists.

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

Only one application per IDeA institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed. For example an IDeA institution could apply as a single entity, as a partnership with other IDeA institutions or as a partnership with one or more eligible institutions as listed above.

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 obtain 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 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
Email:[email protected]
Phone: 301-480-2619

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

• For this specific FOA, the Research Strategy section is limited to 30 pages.

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:

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

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 applicant must demonstrate staff experience and expertise in biostatistics, data management, data analysis, data quality assurance and project management in multicenter research.

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

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

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

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

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

The PD(s)/PI(s) should submit Base Budget estimates for all years including:

• A minimum PD(s)/PI(s) time commitment of 50% (6 person months) should be made. Applications with differing leadership effort commitment plans should document in detail how Network needs will be met.
• Patient and protocol costs.
• Patient and protocol training costs for studies and trials will be supported for distribution to the Clinical Sites.
• Support for required monitoring and DSMB visits, Scientific Oversight Board activities, and ISPCTN Steering Committee meetings.

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

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

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:

Research Strategy:

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

Staffing Plan

The DCOC PD(s)/PI(s) will provide input on study design, data collection, data analysis, and publication of ISPCTN studies. Active participation of the PD(s)/PI(s) is expected during all phases of a research study. The application should describe plans for staffing DCOC functions from protocol design through analysis. The DCOC should have some degree of flexibility in staffing to be able to respond to changing needs and seasonal variation in work effort of the ISPCTN. For instance, meeting deadlines, trial startup and completion, and other variables occur which necessitate increases and decreases in staff effort from the DCOC. Logistical staff for day to day functioning of the Network and support staff to manage Clinical Site patient and protocol costs must be described and justified.

Professional Development Experience

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

Management of Data and Communications

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

Reporting

Applicants must describe plans for generating monthly reports on subject enrollment for multiple concurrent studies, reports for use by the DSMB and the Scientific Oversight Board, and reports for Steering Committee meetings. Documentation and dissemination of meeting minutes and minutes of selected conference call meetings are required to be performed in a timely manner. The applicant should delineate previous history of such activities in the application. Further, experience in preparing data and manuscripts for publication is to be described. The DCOC PD(s)/PI(s) will give a report to the NIH and the Steering Committee quarterly at the Steering Committee meetings, as necessary, including a quarterly report of protocol fund distributions and outstanding invoices.

Logistical and Other Support Services

Applicants must describe plans for logistical and support services relevant to the ISPCTN. Describe plans for providing arrangements for logistical support associated with Steering Committee meetings (as many as four per year) and conference calls, DSMB meetings, webinars and other meetings as needed by the ISPCTN, as well as the annual Scientific Oversight Board meeting. The constitution of the external Scientific Oversight Committee will be determined by the Steering Committee, the DCOC, and the NIH Scientific Officers.

Describe plans for providing documentation in the form of minutes for the above mentioned meetings. Describe plans for handling travel arrangements on occasion for selected consultants as needed, and as resources permit. The DCOC will also provide infrastructure and support the ongoing communication of the ISPCTN via email and teleconference. Plans for logistical and support services should reflect expertise in coordinating sample storage and study drug/equipment assignment is required. Describe plans to oversee the patient and protocol funds for the studies and trials and maintains subcontracts with the Clinical Sites for disbursement. The DCOC will prepare a quarterly report of protocol fund distributions and outstanding invoices for the NIH and ISPCTN Steering Committee.

On Site and Off Site Monitoring Ability

Applicants for the DCOC must describe plans for organizing and conducting both onsite and offsite monitoring of research studies. Generation of data errors and needed edits as queries to sites are required. The DCOC needs to ensure that ISPCTN Clinical Sites fully comply with NIH regulatory requirements including Human Subjects Protections, informed consent, reporting of adverse events, human safety and welfare provisions, and FDA requirements as indicated by specific studies. Additionally, overall documentation and coordination of IRB approvals are the responsibility of the DCOC.

Technology Transfer, Data Management and Protocol Training

Applicants are expected to describe plans for technology transfer, data management, and protocol training. The DCOC must be able to assist the Clinical Sites in data management and communication activities. Professional development and technical expertise, as well as experience and resources, must be delineated. Training sessions for specific scientific protocols, ongoing yearly certifications necessary for any ISPCTN studies and data entry will be arranged through the DCOC.

Administration and Management

All partnerships and collaborations, for example between an eligible organization and an IDeA Awardee, should be described in detail. Memoranda or other formal agreements/commitments should be included in Letters of Support.

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

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

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

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

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

There must be a clearly expressed intent to participate in a cooperative manner with other ISPCTN Clinical Sites, the NIH, the DSMB and the Scientific Oversight Board in all aspects of research in a manner consistent with the terms of the award. The prioritization of ISPCTN work at the DCOC must be expressly stated in the application. ISPCTN Clinical Sites are expected to participate in all studies, and the DCOC provides logistic and data support for all projects.

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

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

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 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 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. 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 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 work with PDs/PIs of relevant clinical trials and 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.

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 there a strong scientific premise for the project? 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? Does the project address an important problem or a critical barrier to ensuring increased pediatric participation in clinical trials in IDeA states?

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?

Are the scientific, administrative, statistical and academic qualifications of the PD(s)/PI(s) and the research team at the DCOC, as well as the qualifications of the PD(s)/PI(s) and applicant institution to participate fully as the DCOC for the ISPCTN demonstrated? Do the key personnel possess appropriate and adequate knowledge and experience in areas relevant to the conduct of collaborative clinical research, especially randomized clinical trials, including experience in research design, execution, data management and quality control, preferably in pediatric clinical research? Are the appropriate commitment, availability, and flexibility of staff and PD(s)/PI(s) time for the satisfactory conduct of the studies and ISPCTN activities demonstrated? Are the experience and qualifications of team members who would be responsible for data quality and management activities appropriate? Are the appropriate expertise and capability in biostatistics, the special needs of pediatric subjects, institutions and IRBs, study development and support, data analysis, project management, staff site training, and monitoring/quality assurance procedures described? Is the evidence of management capability, including assessment of the PD(s)/PI(s)' ability to estimate appropriate and reasonable resources for research studies, to manage research resources efficiently during study execution, and to enhance collaboration among the Clinical Sites of the Network adequate? Does the PD(s)/PI(s) possess prior experience in the design, conduct, data analysis, and data management of major collaborative research projects, experience in pediatric research, and successful performance as a data coordinating center in the previous five years?

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?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Are the procedures described for communication and dissemination of information relevant to clinical research trials and protocols adequate? Is the evidence for quality of reporting capabilities in multicenter trials with respect to monthly reports, trial subject enrollment, and DSMB experience provided? Is there evidence for adequate quality of procedures for onsite and offsite monitoring capabilities? Is there evidence for adequate quality of protocol training and data entry training capabilities? Is the ability to arrange meetings, webinars and conference calls well suited for this initiative? Does the application demonstrate the ability for web based system/website establishment and maintenance? Is the ability to generate reports and maintain study records, as required demonstrated? Is the ability to enable electronic posting of data, protocols and intra-network communications described? Is there evidence of technology transfer capabilities and of capability for support of publicly utilizable datasets?

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

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 (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 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.

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.

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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.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.

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 DHHS, 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:

• Development and initiation of a relevant professional development program.
• Cooperating with the clinical investigators at the ISPCTN Clinical Sites, and with the Project Scientists, Program Official, and other participating NIGMS and NICHD staff, in the design and conduct of protocols, analysis of data, and reporting of results of Network research.
• Administration of scientific protocol funds to the ISPCTN sites with NIH approval.
• Systems for data collection, analysis, coordination, and quality assurance. Required data summaries will be provided to the Network Steering Committee, the NICHD, the NIGMS, the DSMB, and others as determined by the Steering Committee.
• Logistical services, including provision of study drugs, collection and storage of biological fluids and tissue samples, and other supplies for the conduct of research as may be required.
• The awardee will agree to accept the coordinating role of the group and the participatory and cooperative nature of the collaborative research process, and the decisions of the Steering Committee.
• The DCOC grant will provide research support services to the Clinical Sites comprising the ISPCTN. These will include the establishment and maintenance of a centralized information management system to help the Network Clinical Sites, the Steering Committee, the NICHD, and the NIGMS to edit, store, analyze, publish, and disseminate results from the shared research.
• The DCOC will serve as a central repository for ISPCTN data on all collaborative projects and transfer data in a timely manner to relevant partners. The DCOC will serve as the central repository for all ISPCTN studies and efficiently make the data available for data sharing.
• The DCOC will assist the NICHD/NIGMS Project Scientists, the NICHD Program Official, and the Steering Committee in monitoring research progress, and will work to ensure data integrity, accuracy, security, and accessibility.
• Serving as an ISPCTN liaison for any related ECHO Program activities; the DCOC PD/PI will be an ISPCTN representative on the overall ECHO Program Steering Committee. In addition, the DCOC PD(s)/PI(s) will be a member of 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. It is anticipated that decisions regarding the Data Coordinating and Operations Center activities will be reached by consensus and that the NIH staff members will participate in this process. 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.

Specifically, the NICHD Project Scientist will provide:

• Technical assistance and participate as one voting member of the Steering Committee and all active subcommittees.
• Assistance with the identification of important areas of study.
• Assistance in the development, review and approval of the concept proposals and research protocols of all ISPCTN studies.
• Approval of timelines for protocol development, implementation and completion.
• Assistance in the data analysis process and the development of manuscripts resulting from ISPCTN-supported studies.
• Assistance in the development and review of capitation based budgets, including the identification of study costs and special institutional needs.
• Assistance in the review and evaluation of each stage of the program before subsequent stages are started, in conjunction with the Steering Committee, NICHD Program Official (see below), and the Scientific Oversight Board, and make recommendations to enhance the scientific quality of the work.
• Assistance in the reporting of results in the community of investigators and health care recipients.
• Assistance with the conduct of the trials and other approved 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.
• Collaboration 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 PDs/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 PDs/PIs 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. 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 is selected by the NIH Project Scientists, 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 Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)

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

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

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)

Telephone: 301-710-0267

Robert Tamburro, M.D., MSc
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-480-2619
Email: [email protected]

Regine Douthard, M.D., MPH
National Institute of General Medical Sciences (NIGMS)
Telephone: 301-435-1759
Email: [email protected]

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