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) invites applications to participate in a research program cooperative agreement to support the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN). The network will have the capacity to develop and conduct innovative behavioral, community-based, translational, therapeutic, microbicide and vaccine trials in HIV-at-risk and HIV-infected youth ages 12 to 24 years, with a focus on the inclusion of minors. Investigators with innovative thinking and new approaches to address the public health issues facing adolescents are encouraged to apply.

The objective and overarching goal of this initiative is to increase the numbers of at-risk youth who are aware of their serostatus, and for those who are diagnosed with HIV, to increase the numbers in each segment of the care continuum to 95% and to bend the infection rate curve downward toward zero through the efforts of this Network.

This FOA builds on the ATN’s previous work (1994-2016) by encouraging a more focused, innovative, basic and clinical research agenda. For the next ATN cycle there will be a strongly renewed focus on an urgent public health issue in the United States the HIV epidemic in youth.

This FOA solicits applications for the ATN Coordinating Center (CC)(U24) which will provide the necessary support, coordination and operational infrastructure for up to 5 US ATN Cooperative Program Project U19s (funded under a separate FOA).

Greater than of all new HIV infections in the US occur in youth. These infections are disproportionately distributed among ethnic/racial minorities and men who have sex with men (MSM), with more than of new infections occurring in young African American and Hispanic populations and 72% in young MSM populations. These groups are also unique compared to all others because longitudinal trends of infection over the last decade have increased. CDC guidelines for routine HIV testing across the US have increased the numbers of people identified with undiagnosed HIV infection, however up to 80% of youth are unaware of their infection. Additionally, establishing a durable linkage to care, an activity associated with improved outcomes, remains an elusive goal for many providers. This issue is especially important in vulnerable populations like youth, who may encounter more obstacles and challenges when attempting to access care. A significant portion of the youth targeted for the ATN studies will include traditionally difficult to reach populations of medically disenfranchised, low socio-economic status, sexual and gender minority and/or racial/ethnic minority young men and women.

The ATN Coordinating Center (CC) will support the ATN Executive Committee as it executes its responsibilities which include, but are not limited to, the integration of efforts across the ATN U19s and facilitation of transdisciplinary research. The CC will provide infrastructure and organizational support for the ATN's cross-U19 collaborative Projects and other external collaborations.

The CC will facilitate transdisciplinary research through organizational leadership and support of an adolescent-specific research agenda with emphasis on efficient communication, coordination of efforts and scientific collaboration across multiple research projects and institutions in ATN. This will include but is not be limited to: participant accrual, staff and site training, quality assurance procedures including necessary site monitoring, and the operation and integrity of the cross-U19 and other collaboration study databases. Additionally, as determined by NIH, the ATN CC will provide funding for high priority study protocols and collaborations that emerge as major scientific gaps in the rapidly evolving HIV/AIDS research landscape.

U19s Multi-Program Project

The ATN is newly designed as a collaborative Network of up to 5 U19s, each of which will support a research program with a well-defined central theme, research focus, or objective(s) to be funded by a separate FOA, and which will draw on support, coordination and operational infrastructure from an ATN CC funded through this FOA.

Each ATN U19 will include 3-4 R01-like Research Projects and may include 1-2 R21-or R03-like pilot projects, along with Core(s) necessary to support the projects. All research projects will directly focus on one or more aspects of primary prevention and/or the continuum of care among adolescents in the US. The U19 research Network will be facilitated by the sharing of ideas, data, and specialized resources, such as equipment, services, and clinical facilities. The Research Projects proposed must be scientifically meritorious, and also complement one another, be synergistic, and support the program's overall theme. Thus, the program's overall scientific merit should be greater than the sum of its parts.

In addition to the research projects contained within each U19, each application will also include a proposal and process for the development of new protocols within the U19 as the science around primary prevention and the continuum of care among HIV-infected youth continues to evolve. Each application will also include brief proposals for one or more studies that require collaboration with other U19s and/or other domestic HIV clinical research networks. These will inform network discussions and planning that will involve the ATN Executive Committee and will be assisted by the ATN CC which will be supported by this FOA.

ATN Executive Committee (EC)

The ATN Executive Committee (EC) will have representation from each U19 PD(s)/PI(s), the ATN CC (U24) PD(s)/PI(s), NIH ICs, and other selected scientific experts. Additionally, a community representative will bring an added layer of community participation and engagement in the research agenda. The ATN EC will oversee the integration of efforts across the U19s though leadership, efficient communication, coordination and scientific collaboration across the multiple participating research institutions, as well as close interaction with NIH program staff members. Furthermore, the ATN EC will assist the network with identifying emergent scientific priorities and will help administer their implementation, with assistance from the ATN CC. It will also help develop cross-U19 collaborations and facilitate collaborations with other networks and investigators. In consultation with NIH scientists, the EC will also consult with an external Ethics Advisory Panel (EAP), as needed.

Single Institutional Review Board (sIRB)

In order to reduce the burden on local IRBs, to streamline the protocol approval process, and to standardize the oversight of human subjects protection in the ATN Studies, the use of a single IRB is strongly encouraged.

External Advisory Group (EAG)

An independent External Advisory Group (EAG) will be convened by the ATN EC with assistance from the ATN CC to review the scientific progress and activities of each U19, as well as for cross-U19 and other collaborations across the Network, with the goal of maintaining the highest level of scientific progress and relevance of proposed and ongoing projects. The EAG may recommend new directions as appropriate. Members will have the scientific expertise but not be affiliated with components of the ATN U19s. The EAG will meet yearly at an ATN Meeting coordinated by the ATN CC. Following these meetings, the EAG will make recommendations in writing regarding scientific progress and activities of the Network to the NIH and the ATN Executive Committee (EC).

U24 ATN Coordinating Center (CC)

A separate award, which will facilitate collaborations through scientific leadership from the ATN EC and organizational support for the Network, including cross-U19 and external collaborations (including management and allocation of resources) for all ATN U19s and will coordinate logistical needs for the Network, is described in more detail under this FOA for the ATN Coordinating Center (CC) (U24) below.

The ATN Coordinating Center (CC) funded under this FOA will provide operational and logistical support infrastructure to a series of U19 Cooperative Research Program awards, funded under a separate FOA, to support a research program with a well-defined central theme, research focus, or objective(s) for the ATN. The award funded under this FOA and the companion FOA will use cooperative agreement mechanisms (see Section VI.2 Cooperative Agreement Terms and Conditions of Award). Close and substantial interactions between the NIH, and the ATN U24 and U19 awardees, are required to accomplish the objectives of the ATN and of this FOA.

All funds for cross-network collaborative and emerging high-priority study protocols to be conducted by the Network's U19's and other external collaborations will be awarded to the ATN CC in the Notice of Grant Award (NOA) as restricted protocol-related expenses. The use of these funds will require prior discussion and approval from NICHD. Upon approval the funds will be released for studies either in increments or full amounts for approved ATN protocols to the ATN CC.

• The ATN CC is responsible for the monitoring and distribution of protocol funds to the ATN U19s.
• The application should provide a performance-based, centralized, equitable, and efficient method for coordinating the distribution of funds with actual subject accrual.
• Full and transparent collaboration, including appropriate sharing of all necessary tools, materials, technologies and other essential methodologies necessary for protocol and program development, implementation and monitoring between the ATN CC and each of the ATN U19 Programs is a critical requirement for the success of the Program.
• Critical features and functions of the CC include, but are not limited to:
• Administrative management and coordination of external collaborations with the network
• Operational support for cross-network U19 protocols, collaborations and other projects (e.g. conduct of trainings, development of manuals of operation, network public relations, maintenance of network website, communications and conference calls, convening committees and meetings, etc.)
• Data management and innovative analytic methodology
• Training on a breadth of research related topics (e.g. regulatory/IND, safety reporting, GCP/GCLP, HSP, etc)
• Management of resources and execution performance-based subcontracts (e.g. material distributors, specimen storage, pharmaceutical vendors, U19 investigators, other collaborators, etc.)
• Provision of a regulatory infrastructure for cross-network U19 protocols, collaborations and emerging projects (e.g. site performance monitoring, quality assurance procedures and protocol registration)
• Provision of mechanisms and metrics to monitor subject screening, recruitment, retention, and dropout, and procedures for adjustment if enrollment targets are not being met
• Provision of a detailed system for regular tracking and reporting of study progress, including a description of performance metrics, milestones, timelines, and quality-control measures to keep the study on track and on budget and which includes strategies to identify and mitigate problems as they arise
• Provision of a data sharing policy with explicit plans, procedures, milestones, and timelines to make the data and bio specimens available for access and analysis by the research community as appropriate

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

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.

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

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

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.

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

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

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

The letter of intent should be sent to:

Bill G. Kapogiannis, MD
Telephone: 301-402-0698
Fax: 301-496-8678
Email: [email protected]

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

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

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

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

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

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

All instructions in the SF424 (R&R) Application Guide must be followed. The application should include costs for post-award kick-off meeting(s) at a convenient location for ATN and NIH staff.

The CC should include in their budget under the Other Expenses category an amount each year for subcontracts to clinical sites.

The budget for the CC should include, at a minimum:

• Level of effort and salary for the PD(s)/PI(s)
• Level of effort and salary for a project manager possessing the scientific and operational content expertise in the conduct of HIV research among adolescents to support the PD(s)/PI(s)
• Administrative support personnel to assist the PD(s)/PI(s) and project manager
• Personnel costs for the efficient support of cross-ATN collaborative studies
• Personnel costs to support/manage ATN studies of emerging high-priority protocols
• Travel funds for two 2-3 day ATN meetings per year

The budget for the CC should also include support for the National Community Advisory Board (CAB) Representative Liaison (on behalf of all U19 CAB Liaisons) to be selected by the ATN EC and provide logistical support to any CAB-associated meetings at the in-person national ATN meeting;

The CC is responsible for the monitoring and distribution of protocol funds for cross-U19 and other collaborations, and high-priority protocols responding to emerging needs. This includes funds distributed through performance-based subcontracts to any sites from which subjects will be recruited, as appropriate.

The CC must propose administrative and management functions that would assure continued attention to cost-efficiency and productivity, including adjustment of resource allocation during protocol performance, to be executed after consultation with and approval by NIH and the ATN EC.

Key Members of the CC are expected to attend monthly group calls, scheduled specific study calls, and semi-annual network and ad hoc group meetings.

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: The PD(s)/PI(s) for the CC should propose an infrastructure and organizational support plan for the ATN to facilitate cross-U19 and other collaborations, and high-priority protocols responding to emerging network priorities.

The application must clearly outline:

• Plans for a project manager possessing the scientific and operational content expertise in the conduct of HIV research among adolescents to support the PD(s)/PI(s) in successfully implementing and achieving the goals of the CC,
• The mechanisms proposed for staff and site training,
• Site-specific subject accrual reimbursement through performance-based subcontracts
• Quality assurance procedures,
• The operation and integrity of the ATN study databases,
• ATN study development and support, for cross-U19 and other network collaborations
• These responsibilities should be presented with plans, processes, and timelines.
• The CC applicant should be able to respond flexibly to the changing needs of the ATN cross U19 protocols as the projects unfold, adding and subtracting staff as the requirements of the protocols dictate. The application should reflect an understanding of these processes.

An application for the CC must provide evidence of data management capabilities by describing standard operating procedures that address:

(1) plans for database design and administration;

(2) plans for data collection, management, and data quality control;

(3) plans for innovative analytic methodology relevant to HIV/AIDS research,

whether provided by the CC or through external performance-based

subcontracts;

(4) plans for the management of external data collected and/or analyzed by ATN U19

or other collaborating investigators themselves;

(5) plans for the provision of a regulatory infrastructure that will support cross-U19

registrational research protocols (including potential IND sponsorship) and which

will cooperate fully with individual U19 awardee's regulatory counterparts for all

needed data submissions to NIH and FDA, in accordance to all applicable federal

requirements; and

(6) plans for providing an electronic communication system to participants of the

ATN, including the design of an ATN website where necessary resources for the

Network and collaborating investigators and which allows separate access to the

public.

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

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• The Data Sharing Plan is expected to address the explicit milestone of making data available for this purpose within one calendar year of study/research project completion.
• Applicants are expected to deposit biospecimens in the ATN Network Repository for storage and use, consistent with achieving the goals of the program. NICHD holds the exclusive authority to enter into agreements with outside parties for the purpose of sharing data and biospecimens in accordance with NIH policies. Therefore, awardees shall not enter into any third party agreements directed to aspects of an active study with any outside party, during the course of the study.

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

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.

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?

Do the qualifications and research experience of the project manager demonstrate scientific and operational content expertise in the conduct of HIV research among adolescents to appropriately support the PD(s)/PI(s) in successfully implementing and achieving the goals of the CC? Are the qualifications and research experience of the management and team adequate? Is the previous experience with design, administration, management, and coordination of multi-center clinical studies or trials adequate? Are the proposed resources and personnel for supporting the ATN adequate?

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?

If CC is proposing internal analytic capacity, is there demonstration of innovative

approaches to evaluating clinical research data?

Is there demonstration of innovative approaches to the management of clinical research data?

Is there demonstration of innovative approaches to providing operational support for a multi-site clinical research network to undertake expedient scientific protocol development and implementation?

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?

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?

For cross-U19 and other collaborations, and high-priority protocols responding to emerging needs:

Are site set-up and staff training plans adequate?

Are plans to respond to the changing data management and analytic needs of the ATN, including for complex collaborations and cross-U19 registrational trials, flexible?

Are the plans to guarantee the quality and integrity of collected data adequate?

Are there adequate plans for a full and transparent collaboration, including appropriate sharing of all necessary tools, materials, technologies and other essential methodologies necessary for protocol and program development, implementation and monitoring between the ATN CC and each of the ATN U19 Programs?

Are plans to maintain accurate and timely information on the progress of studies and site performance adequate?

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?

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.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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

Not Applicable

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 Wide Association Studies (GWAS) /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 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 National Advisory Child Health and Human Development Council (NACHHD). 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.
• Compliance with data and resource sharing policies as appropriate.

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) and project manager will have the primary responsibility for:

ATN Coordinating Center (CC)

The Coordinating Center (CC) will consist of the Principal Investigator(s), project manager, and staff deemed necessary to carry out the mission of the CC. The CC project manager will coordinate the activities of the CC at the direction of the principal investigator.

The CC will:

• Provide methodologic and analytic support for the development of independent research projects, design the corresponding data collection forms and database(s), maintain the database(s) and supply the required analytic capacity, either directly or through performance-based subcontracts;
• Supervise all data collection procedures by the ATN U19's, arranging for combined efforts when indicated by regulatory demands of collaborative research, including transmission and storage of data to central location;
• Provide for the most efficient transfer of study data generated by collaborative research either by maintenance of all necessary study-associated database(s) with their electronic transfer or arranging for on-site data entry for the designated the U19's;
• Provide data management and integrity, harmonization and sharing across U19s for cross-network protocols, collaborations and related projects and share such methods with ATN U19s and collaborators;
• Conduct protocol and site registration and other regulatory duties as delegated from NICHD, including executing data use agreements to protect ATN data and subject rights;
• Establish and support Data and Safety Monitoring Boards (DSMB), protocol safety monitoring committees and other functional groups, when instructed by NICHD;
• Provide training, including the development and updating of study manuals of operation, to all personnel related to acceptable quality control and quality assurance procedures at the sites as well as protocol-training where indicated;
• Provide on-site monitoring for those studies being performed at a particular site on a schedule dictated by the EC, its authorized subcommittee or NICHD, as regulatory needs arise (e.g. registrational/IND trials);
• Support the National Community Advisory Board (CAB) Representative Liaison (on behalf of all U19 CAB Liaisons) to be selected by the ATN EC and provide logistical support to any CAB-associated meetings at the in-person national ATN meeting;
• Participate in regular conference calls and attend meetings to be held at least semi-annually.
• Maintain the ATN protocol disbursement fund and execute all necessary agreements to support study and subject accrual costs for cross-U19 protocols and collaborations, reconciling reimbursement to site performance, in consultation with the NICHD Project Scientist.;
• Collaboratively plan and conduct all recurring EC and ATN meetings and work with other ATN U19 PIs and NIH to assemble and convene the ATN External Advisory Group (EAG) at least annually;
• Coordinate and implement necessary protocol activities including protocol trainings, workshops, etc. for cross-network protocols, collaborations and other projects
• Provide administrative management and coordination of external collaborations with the network
• Provide operational support for the network public relations and media interviews in coordination with the participating NIH Institutes, dissemination and education priorities, communications within the network such as listserv e-mail, formation of subcommittees (on topics such as ascertainment and sampling, publications, clinical issues), and conference calls;
• Provide for mechanisms to monitor subject recruitment, retention, and dropout, and develop procedures for adjustment if enrollment targets are not being met;
• Provide for a detailed system for regular tracking and reporting of study progress, including a description of performance metrics, milestones, timelines, and quality-control measures to keep the study on track and on budget; this system must also include strategies to identify and mitigate problems as they arise;
• For cross-U19 and other collaborations, and high-priority protocols responding to emerging needs, develop and ensure that the ascertainment and sampling strategies are appropriate for the stated goals of the research project, solicit appropriate epidemiological expertise as needed;
• Develop and maintain policies for presentation (e.g., at scientific conferences) and publication of findings in peer-review journals from the consortium’s research activities;
• Work with the ATN EC to produce and maintain documentation of Network manual of operations which includes standard operating procedures and training manuals;
• Develop and maintain a web site to publicize Network activities and provide a venue for public access to available Network resources;
• Provide for the consultation of dedicated expertise and plans to address the various bio-ethical issues and concerns (e.g., handling of sensitive data, participatory risk, involvement of vulnerable populations, incidental findings, early substance use or substance use problems in study participants) that are likely to arise during the conduct of the research;
• Provide a data sharing policy with explicit plans, procedures, milestones, and timelines to make the data and bio specimens available for access and analysis by the research community, as appropriate and in accordance with NIH policies and guidance;
• Fully and transparently collaborate, including appropriate sharing of all necessary tools, materials, technologies and other essential methodologies necessary for protocol and program development, implementation and monitoring between the ATN CC and each of the ATN U19s.

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

NIH Project Scientists will represent each of the institutes co-sponsoring the FOA.

The NIH Project Scientists will:

• Facilitate the exchange of information between the ATN and other existing research networks to support collaborative efforts;
• Participate in the ATN EC that oversees the establishment, maintenance and collaborative scientific efforts of the ATN and its progress in achieving program goals;
• Assist the ATN EC in monitoring the progress of ongoing studies, including field data collection, standardization of methods across study sites, and adherence to protocol and quality control measures;
• Assist the ATN EC in the selection of research topics, and the development or review of protocols for specific studies and interventions;
• Assist the ATN EC in identifying ATN resources required for the successful implementation of collaboratively developed research protocols;
• Arrange Program review of all new ATN protocols developed during the project cycle and, when necessary, the external peer review of the protocols, clearing these studies for implementation;
• Assist in data analyses, interpretation, and publication of study results;
• Assist in identifying the need to terminate or curtail the study (or an individual award) in the event of nonparticipation in the committee/group activities, substantial shortfall in participant recruitment, follow-up, data reporting, quality control, or other major breach of protocol, or substantive protocol changes without prior approval from NIH Program or the ATN Executive Committee.

Additionally, 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.

The duties of the agency Program Official include:

• Carry out continuous review of all activities to ensure that the 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.
• Perform other duties required for normal program stewardship of grants.

Areas of Joint Responsibility include:

ATN Executive Committee (EC)

The ATN EC will consist of the PD(s)/PI(s) from each U19, the PD(s)/PI(s) from the ATN Coordinating Center (CC) (U24), the NIH project scientists and other selected scientific experts as agreed to by the EC. Additionally, a community representative will bring an added layer of community participation and engagement in the research agenda. A Principal Investigator from one of the U19s will be elected by the EC to serve as chair of the group. A vice-chair will also be elected by the EC. The ATN EC will oversee the integration of efforts across the U19s through leadership, efficient communication, coordination and scientific collaboration across the multiple participating research institutions, as well as close interaction with NIH program staff members. The ATN EC will have the primary responsibility for identifying emerging scientific priorities, defining the cross-U19 and other collaboration research agenda, and implementing these in the network, and initiating and maintaining collaboration across U19s and with other NIH-funded HIV-related research networks within the guidelines of this FOA. The EC will retain custody of and have primary rights to the data and software developed under such cross-U19 and other collaborations, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

Each full member will have one vote. Each NIH IC project scientist will also have one vote.

Awardee members of the ATN Executive Committee will be required to accept and implement policies approved by the ATN Executive Committee.

Specifically, the EC will:

• Draft, review and maintain all current ATN-wide policies and procedures in the ATN Manual of General Operations; any ATN Executive Committee-approved and NICHD-acceptable revisions of the Manual during the project period of these awards will supersede the provisions of these specified terms of award;
• Implement and enforce, either directly or through delegation to other ATN-supported personnel, a Conflict of Interest (COI) Policy acceptable to the Maternal and Pediatric Infectious Disease Branch, NICHD, that addresses any COI that may occur or may be perceived to occur through financial interest or other associations between members of the ATN and the private sector to ensure compliance with all Federal regulations and NIH policies applying to the conduct of research involving human subjects (these include, but are not limited to, Title 42 CFR 50 and Title 45 CFR 46). NICHD notes that the primary regulatory authority for enforcement of the COI Policy belongs to the grantee institution and NICHD does not intend by this term of award to abrogate that responsibility. Rather, NICHD is imposing on the ATN an additional responsibility to protect the integrity of the research produced by the ATN. Therefore, if either the ATN EC or the grantee institution identifies a real or perceived COI, both the ATN EC and the grantee institution must address the COI and inform NICHD of the resulting action;
• Execute all Memoranda of Understanding or Agreement with other entities to conduct ATN developed or co-endorsed research;
• Work with all ATN U19 PD(s)/PI(s)s to adopt and, if necessary, revise the current ATN policies and procedures for elected terms of office and voting procedures, protocol development and review, authorship and publication, collaboration, site and, where indicated, laboratory monitoring, repository requirements, and related issues and review these for approval;
• Work with the U19 PD(s)/PI(s), the ATN CC PD(s)/PI(s) and NIH Project Scientists to identify the most efficient and scientifically sound mechanisms for developing the research agenda as needs emerge during the project cycle, deciding if the specific agenda items are best pursued independently in the ATN, given resources, implement high priority protocols across several or all ATN U19s, and/or in collaboration with existing research networks;
• Coordinate ATN collaboration with investigators with funding from sources other than NIH-funded networks;
• Be responsible for the fiscal management and tracking of all network resources, either directly or through establishment of a specific subcommittee tasked with this function in an iterative and continuous manner, through a collaborative effort with the ATN CC;
• Approve use of discretionary funds as recommended by NIH;
• Develop a formal liaison with leaders of other appropriate HHS-supported HIV prevention and clinical trial networks to facilitate early interaction and communication in protocol design that address key questions in the adolescent population;
• Develop formal communication and liaison with existing HHS-supported prevention and clinical trials networks to inform the ATN leadership on protocols of interest; to define and resolve key logistical issues (e.g. data collection and transfer, drug repository and regulatory requirements; negotiate shared study costs;) which must be addressed to facilitate adolescent enrollment in collaboratively developed research protocols;
• Supervise progress, with the assistance of the NICHD staff, of the U19 PD(s)/PI(s) in identifying resources within the ATN to support subject recruitment, enrollment, retention, data collection, specimen shipping, and negotiated protocol monitoring costs for ATN-approved protocols and in recommending to NICHD the use and, as necessary, the reallocation of funds for such support;
• Participate in regular conference calls and attend ATN meetings to be held at least semi-annually.
• For cross-U19 and other collaborations, and high priority protocols responding to emerging needs, the EC will:
• Retain the primary responsibility for defining and prioritizing the research agenda in collaboration with the NIH Project Scientists;
• Approve the direction of the research effort including any reconfiguration of research subgroups or working groups to better address the direction of the scientific agenda, and oversee the conduct and monitoring of the studies;
• Assist U19 PD(s)/PI(s) in oversight of site participation and performance, informing the appropriate program managers and taking necessary actions in accordance to ATN policies and procedures.
• Commit to the development of preventive and therapeutic adolescent-focused studies that take into account the needs and capacities of this special youth population through active consultation with local SRVs and their communities, as needed;
• Interact, coordinate, and, where indicated, contract with immunology and virology laboratories participating or willing to participate in NIH-supported quality assurance programs in order to provide the ATN with necessary laboratory support for independent ATN studies;
• Take responsibility for optimizing the Network’s collaboration through the overall scientific merit of components of the research agenda
• Negotiate any ATN rights to data and authorship with executive bodies of collaborating networks and external investigators;
• Additionally, 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.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual 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: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Bill G. Kapogiannis, MD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-402-0698
Email: [email protected]

Richard Jenkins, PhD
National Institute on Drug Abuse
Telephone: 301-443-1923
Email: [email protected]

Susannah Allison, PhD
National Institute of Mental Health (NIMH)
Telephone: 240-627-3861
Email: [email protected]

Francisco S. Sy, MD, DrPH
National Institute on Minority Health and Health Disparities
Telephone: 301-402-1366
Email: [email protected]

Sherry Dupere, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-451-3415
Email: [email protected]

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

Pamela Fleming
National Institute on Drug Abuse
Telephone: 301-253-8729
Email: [email protected]

Rita Sisco
National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email: [email protected]

Priscilla Grant\
National Institute on Minority Health and Health Disparities (NIMHD)
Telephone: 301-594-8412
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.