Adolescent Medicine Trials Network for HIV/AIDS Interventions

RFA Number: RFA-HD-04-025

Part I Overview Information

Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations
National Institute of Child Health and Human Development (NICHD), (http://www.nichd.nih.gov)
National Institute on Drug Abuse (NIDA), (http://www.nida.nih.gov)
National Institute of Mental Health (NIMH), (http://www.nimh.nih.gov)

Announcement Type
This is a reissue of RFA-HD-00-002, originally published on February 14, 2000

Update: The following update relating to this announcement has been issued:

Catalog of Federal Domestic Assistance Number(s)
93.865, 93.242, 93.279

Key Dates

Release Date: November 24, 2004
Letters Of Intent Receipt Date(s): February 25, 2005
Application Receipt Dates(s): March 25, 2005
Peer Review Date(s): June/July 2005
Council Review Date(s): September 2005
Earliest Anticipated Start Date: March 1, 2006
Additional Information To Be Available Date (Url Activation Date): December 1, 2004
Expiration Date: March 26, 2005

Due Dates for E.O. 12372
Not Applicable

Executive Summary

The National Institutes of Child Health and Human Development (NICHD), Drug Abuse (NIDA), and Mental Health (NIMH) invite applications from investigators willing to participate with NICHD, NIDA, and NIMH under a cooperative agreement to sustain the Adolescent Medicine Trials Network (ATN). This network will have the capacity for developing and conducting selected behavioral, community-based translational, prophylactic, therapeutic, and vaccine trials.

The primary mission of the Adolescent Medicine Trials Network (ATN) for HIV/AIDS Interventions will be to conduct research, both independently and in collaboration with existing research networks and individual investigators, in HIV-infected and HIV-at-risk pre-adolescents, adolescents, and young adults up to age 25 years.

The NICHD intends to commit approximately $20 million, NIDA intends to commit $1 million, and NIMH intends to commit $750,000 in total costs [Direct plus Facilities and Administrative (F & A) costs] in FY 2006 to support 16 to 19 new and/or competing continuation grants in response to this RFA. This RFA will use the NIH Cooperative Research Project Grant (U01) award mechanism.

Applications may be submitted if an institution has any of the following characteristics:

Applicant institutions must be providing multidisciplinary, youth-friendly, primary health care to HIV-infected young people grounded in the principles and practice of adolescent medicine.

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with his/her institution 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 programs. Individuals may submit an application for one or more structural components of the ATN: the ATN Coordinating Center, the ATN Data and Operations Center, or the ATN Trials Units.

Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001). The PHS 398 is available at http://www.grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.     

Telecommunications for the hearing impaired: TTY 301-451-5936

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

  Section I. Funding Opportunity Description
    1. Research Objectives

  Section II. Award Information
    1. Mechanism(s) of Support
    2. Funds Available

  Section III. Eligibility Information
    1. Eligible Applicants
      A. Eligible Institutions
      B. Eligible Individuals
    2.Cost Sharing
    3. Other - Special Eligibility Criteria

  Section IV. Application and Submission Information
    1. Address to Request Application Information
    2. Content and Form of Application Submission
    3. Submission Dates
      A. Receipt and Review and Anticipated Start Dates
        1. Letter of Intent
      B. Sending an Application to the NIH
      C. Application Processing
    4. Intergovernmental Review
    5. Funding Restrictions
    6. Other Submission Requirements

  Section V. Application Review Information
    1. Criteria
    2. Review and Selection Process
    3. Merit Review Criteria
      A. Additional Review Criteria
      B. Additional Review Considerations
      C. Sharing Research Data
      D. Sharing Research Resources

  Section VI. Award Administration Information
    1. Award Notices
    2. Administrative Requirements
     A. Cooperative Agreement Terms and Conditions of Award
        1. Principal Investigator Rights and Responsibilities
        2. NIH Responsibilities
        3. Collaborative Responsibilities
        4. Arbitration Process
    3. Award Criteria
    4. Reporting

  Section VII. Agency Contact(s)
    1. Scientific/Research Contact(s)
    2. Peer Review Contact(s)
    3. Financial/ Grants Management Contact(s)

  Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement
Section I. Funding Opportunity Description

1. Research Objectives

The National Institute of Child Health and Human Development (NICHD), National Institute on Drug Abuse (NIDA), and National Institute of Mental Health (NIMH) invite applications from investigators willing to participate with NICHD under a cooperative agreement to sustain the Adolescent Medicine Trials Network (ATN). This network will have the capacity for developing and conducting selected behavioral, community-based translational, prophylactic, therapeutic, and vaccine trials based on and adding to the information developed through the Adolescent Medicine HIV/AIDS Research Network (1994-2001) and the current Adolescent Trials Network for HIV/AIDS Interventions (2001-2006). The primary mission of the Adolescent Medicine Trials Network (ATN) for HIV/AIDS Interventions will be to conduct research, both independently and in collaboration with existing research networks and individual investigators, in HIV-infected and HIV-at-risk pre-adolescents, adolescents, and young adults up to age 25 years. Prevention research and not the development of antiretroviral therapy trials will be the primary focus of research for pre-adolescents. Much of the research activity of the ATN will focus on collaboration with the Clinical Trials Networks supported by the Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID) through coordination of research. The ATN will bring expertise and resources to collaborative protocol development that will ensure feasible and acceptable study design as well as experience in recruiting and retaining this unique population. This initiative calls for a broad array of intervention studies aimed at the primary, secondary, and tertiary prevention of HIV infection in pre-adolescents, adolescents, and young adults at clinical sites and in their surrounding communities. The objective of this Request for Applications (RFA) is to continue and expand the infrastructure required for a network of 14-17 clinical sites, one data and operations center, and one scientific leadership group with discipline-specific subgroups. This network will design, develop, and conduct multiple common clinical trials as well as pertinent formative and translational research studies collaboratively or independently when needed. This network will bring the required numbers of subjects into rigorously designed common protocols and thus address pressing research questions in youth more quickly than could individual centers acting alone.

Research Objectives

Background

An estimated 11.8 million young people aged 15 to 24 are living with HIV/AIDS worldwide and each day another 6,000 young people are newly infected. In the US, the rate in youth remains among the highest. These infections are disproportionately among ethnic/racial minorities, with infections in women outnumbering those in men in reported cases. Adding to these are increasingly large numbers of HIV positive children, infected from birth, and entering adolescence with its attendant developmental issues. The Adolescent Trials Network (ATN) for HIV/AIDS Interventions is the first clinical research infrastructure to address the particular challenges and unique clinical management demands of HIV-infected adolescents and the prevention needs of at risk youth through common protocols. The ATN has undertaken studies to interrupt HIV transmission in uninfected youth. The Connect-to-Protect (C2P) Program is developing the primary prevention infrastructure called for in an NIH-Community Consultation on what racial and ethnic minorities will require to accept HIV prevention vaccine research in youth. This effort, in collaboration with staff from Centers for Disease Control and Prevention (CDC), is being implemented.

Secondary prevention studies examine ways to preserve health in HIV-infected populations, including management strategies like short cycle antiretroviral therapy and the evaluation of Hepatitis B (HBV) immunization schedules. Studies are needed in key areas: long-term effects of newer therapies administered during growth and sexual maturation periods are unknown; exploration of adolescent-specific HIV pathogenesis is needed; and the potential for immune recovery through the study of therapeutic vaccines and immune-based therapies requires evaluation. As more effective agents are used widely in youth, improved survival may permit HIV-induced malignancies to emerge, particularly those resulting from co-infection with human papillomavirus (HPV) or HBV; relevant therapeutic strategies to address these possible co-morbidities are needed.

Tertiary prevention studies are needed to restore ill HIV-positive youth to full or better function. All HIV-infected youth are faced with social and physical developmental challenges of puberty that make coming to terms with chronic illness, complex drug regimens, and disclosure to peers an intensely more complicated endeavor. There are few adolescent-specific studies to improve treatment adherence, and to prevent or minimize the negative consequences of HIV infection, particularly during the critical developmental periods of adolescence. The ATN is systematically evaluating the major difficulties adolescents have with adherence to antiretroviral regimens. Special attention is needed for the emerging behavioral problems of perinatally-infected adolescents who experience all of the socio-behavioral difficulties of their sexually-infected peers, but also face unique clinical management problems given past multiple drug regimen failures. The ATN is addressing these special needs through studies designed with chronic disease specialists.

The ATN's current agenda needs to be sustained and expanded to meet the emerging needs of this population. The ATN has been able to identify, develop, and implement a broad research agenda consisting of formative and adaptive behavioral research studies, community-based epidemiologic needs assessments, and therapeutic pilot studies and trials. NICHD, NIDA, and NIMH intend to work with ATN investigators to further the HIV research agenda for American youth in two major ways: (1) by meeting the clinical management and behavioral needs of HIV-infected youth, and (2) by establishing a community-based primary prevention infrastructure that might support HIV preventive vaccine clinical trials as one of its prevention strategies. To accomplish these goals fully, NICHD, NIDA, and NIMH will coordinate the development of the ATN's research agenda and the use of its available resources with the Clinical Trials Networks supported by the Division of AIDS, NIAID.

Scope

This initiative calls for a broad array of interventional studies, conducted collaboratively and independently when needed, aimed at the primary, secondary, and tertiary prevention of HIV infection in pre-adolescents, adolescents, and young adults at the trials units in the network. Primary prevention studies will focus on efforts to interrupt HIV transmission in uninfected populations. This will be accomplished by establishing a community-based primary prevention infrastructure that will be able to support clinical trials evaluating HIV preventive vaccines and other biomedical modalities as part of its menu of prevention strategies tailored for youth at greatest risk for HIV infection or transmission. These strategies include, but are not limited to, interventions in the following areas:

Secondary prevention studies examine behavioral and therapeutic interventions in order to preserve health and function in HIV-infected populations. These include, but are not limited to, studies in the following areas:

Tertiary prevention studies evaluate strategies to restore ill HIV-positive adolescents and young people to full or better function. These studies include, but are not limited to, the following areas:

Studies on all three levels should be interdisciplinary collaborations to address the complexity of the population and co-occurring health problems, such as STD infection, alcohol and substance abuse, and mental or neurocognitive disorders.

Organizational Components

The Adolescent Medicine Trials Network (ATN) for HIV/AIDS Interventions will consist of the Adolescent Medicine Coordinating Center (ACC) whose responsibility is to establish the Adolescent Medicine Leadership Group (AMLG); a Data and Operations Center (DOC); and Adolescent Medicine Trials Units (ATUs). The AMLG may have subgroups; the structure of these subgroups should be driven by the nature of the research proposed in the application. Currently, the AMLG is comprised of three subgroups to implement the research agenda (Therapeutics, Behavior, and Community Prevention). Any organized ancillary groups that support the development or review of the proposed research should be described in the application. Current ancillary groups include the Study Coordinator Group, the Connect-to-Protect Coordinators Group, the Community Advisory Board, Data and Safety Monitoring Board(s) (DSMB), and the Ethics Advisory Panel. ATN Network governance and coordination will be provided by an Executive Committee, comprised of the Principal Investigator and Project Director of the ACC, the Vice Chair(s) for any AMLG subgroup, the Principal Investigator and Project Director of the DOC, the Chair and Vice Chair of the Adolescent Medicine Trials Units Principal Investigators, and the NICHD project scientist. (Other NIH scientists, Chairs and Vice Chairs of ancillary clinical and community coordinator groups, and the staff person of the Community Advisory Board serve as non-voting ad hoc members.) The Executive Committee will enforce the established policies and procedures of the ATN. The ATN policies can be retrieved at http://www.atnonline.org/, a website operated by the currently-funded ATN.

Network Responsibilities

The Principal Investigator (PI) of the Adolescent Medicine Coordinating Center (ACC) is responsible for assembling, through performance-based subcontracts, the necessary multidisciplinary team of established investigators from within and outside of the PI's home institution to participate in the Adolescent Medicine Leadership Group (AMLG) and to set the research agenda for the network, and clearly outline the priority areas, plans, processes, and timelines for achieving the implementation of the proposed agenda. The proposed research agenda should address the full spectrum of trials included in the purpose for establishing the ATN (viz. behavioral, therapeutic, vaccine, microbicidal, and community prevention trials). The AMLG is responsible for the peer review of studies proposed for implementation within the ATN with additional review at the program level. NICHD will specify when a study requires a DSMB to oversee the research activities. The AMLG establishes and maintains collaborative relationships with other research networks in order to implement the full research agenda. Members of the AMLG groups are expected to attend monthly group calls, scheduled specific study calls, and semi-annual network and ad hoc group meetings.

The Adolescent Medicine Data and Operations Center (DOC) has the responsibility to provide the ATN's infrastructure and organizational support including the funding of study needs and subject accrual to protocols at the clinical sites, staff and site training, quality assurance procedures including site monitoring, ATN study development and support, the operation and integrity of the study databases, analytic capacity, and regulatory adherence through protocol and site registrations procedures. Members of the DOC are expected to attend monthly group calls, scheduled specific study calls, and semi-annual network and ad hoc group meetings. Funds for travel should be requested within the proposed budget.

It is important to note that funds for study protocols to be conducted by the individual Adolescent Medicine Trials Units (ATUs) will be awarded in the ATN DOC Notice of Grant Award (NGA) rather than each ATU NGA. The use of these funds will require prior approval from NICHD program and grants management; approval will release these funds for studies either in increments or full amounts for approved ATU protocols to the ATN DOC. The ATN DOC is responsible for the monitoring and distribution of protocol funds to the ATU as a fee for service arrangement. This mechanism will provide a centralized, equitable, and efficient method for coordinating the distribution of funds with actual subject accrual.

The Adolescent Medicine Trials Units (ATUs) have the responsibility of ATN subject recruitment, retention, and safety through their capacity to provide a wide array of adolescent-specific services by multidisciplinary clinical staffs in well-established adolescent medicine, HIV-care experienced clinical sites. The ATUs enroll and monitor subjects in ATN-supported studies, and provide guidance and counsel on the acceptability and feasibility of proposed network research. ATUs are required to cooperate with site monitoring teams, to discharge remote data capture responsibilities and adhere to ATN policies and procedures. Principal investigators, and clinical and community study coordinators are expected to attend monthly group calls, scheduled specific study calls, and semi-annual network and ad hoc group meetings. Funds for travel should be requested within the proposed budget.

Section II. Award Information

1. Mechanism(s) of Support

This funding opportunity will use the NIH Cooperative Research Project Grant (U01) award mechanism(s). As an applicant, you will be responsible for planning, directing, and executing the proposed project .

The NIH U 01 is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award."

2. Funds Available

The NICHD intends to commit approximately $20 million, the NIDA intends to commit $1 million, and the NIMH intends to commit $750,000 in total costs [Direct plus Facilities and Administrative (F & A) costs] in FY 2006 to support 16 to 19 new and/or competing continuation grants in response to this RFA. An applicant for the ATN Coordinating Center (ACC) may request a project period of up to five years and budget for direct costs of up to $1.5 million per year. An applicant for the ATN Data and Operations Center (DOC) may request a project period of up to five years and budget for direct costs of up to $2 million per year. An applicant for a re-competing ATN Trials Unit may request a project period of up to five years and a core budget for direct costs of up to $480,000 per year to maintain the infrastructure required to perform multiple protocols. A new applicant for an ATN Trials Unit may request a project period of up to five years and core budget for direct cost of up to $250,000 per year to establish the infrastructure required to perform multiple protocols. Future year budgets may be escalated at three percent for recurring costs. Funds to support actual protocol accrual will be managed and distributed by the Adolescent Medicine Data and Operations Center (DOC) to each participating ATN Trials Unit as a fee-for-service arrangement after a protocol has been approved by the ATN and the NICHD has approved the funds for distribution. Requests for protocol funds should not be included in the application, but will be negotiated at a later date. Because the nature and scope of the proposed research activities will vary from site application to site application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the NICHD, NIDA, and NIMH provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

Applicant institutions for ATUs must be providing multidisciplinary, youth-friendly, primary health care to HIV-infected young people grounded in the principles and practice of adolescent medicine.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution 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 programs.

2. Cost Sharing
Cost sharing is not required.

3. Other-Special Eligibility Criteria

Individuals are eligible to submit an application for one or more structural components of the ATN: the ATN Coordinating Center, the ATN Data and Operations Center, or the ATN Trials Units.

Applications for ATN Trials Units should include a primary site only; consortium or sub-site arrangements will not be accepted and such applications will be considered non-responsive to the RFA. Multiple practice sites for the research staff at the primary site are acceptable; future direct funding of these secondary sites is possible and will follow evidence of accrual to ATN studies.

Section IV. Application and Submission Information

1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001; 9/2004 version after May 10). Applications must have a Dun and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

See Section VI.2. Administrative Requirements for additional information.

The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.

3. Submission Dates
Applications must be received by March 25, 2005.

3.A. Receipt, Review and Anticipated Start Dates

Letters Of Intent Receipt Date(s): February 25, 2005
Application Receipt Dates(s): March 25, 2005
Peer Review Date(s): June/ July 2005
Council Review Date(s) : September 2005
Earliest Anticipated Start Date: March 1, 2006

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

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.

The letter of intent is to be sent by the date listed at the beginning of this document.

The letter of intent should be sent to:

Audrey Smith Rogers, Ph.D.
Pediatric, Adolescent and Maternal AIDS Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 4B11, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 435-6873
FAX: (301) 496-8678
Email: Audrey.rogers@nih.hhs.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the PHS 398 research grant application instructions and forms as described above. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Robert Stretch, Ph.D.
Director, Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard , 5B01, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service)

Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf.

3.C. Application Processing

Applications must be received on or before the application receipt date listed in the heading of this funding opportunity. If an application is received after that date, it will be returned to the applicant without review. Applications will be evaluated for completeness by CSR.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.

4. Intergovernmental Review
This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm (See also Section VI.3. Award Criteria).

6. Other Submission Requirements

•  Specific Application Requirement for ATN Coordinating Center (ACC)

An application for the ACC is submitted by an institution on behalf of the Principal Investigator of the ACC who should propose a research agenda for the ATN in the application, clearly outlining the priority areas in depth, discussing plans, processes, and timelines for achieving the implementation of the proposed agenda, and assembling the necessary multidisciplinary team of established investigators from within and outside of the PI's home institution. Disciplines should be included as required to support the proposed research agenda. The proposed research agenda should address the full spectrum of trials listed in the NICHD's, NIDA's, and NIMH's purpose for establishing the ATN (viz. behavioral, prophylactic, therapeutic, vaccine, and microbicidal trials).

Evidence of potential collaborative relationships with other research networks should be provided. Applicants are encouraged to consider, in particular, relationships with research networks supported by the Division of AIDS, National Institute of Allergy and Infectious Diseases. The budget for the ACC should include, at a minimum, salary and administrative support for the Coordinating Center, AMLG and its operations, and travel to two three-day ATN meetings per year. Future year budgets may be escalated at 3 percent for recurring costs.

The ACC PI should also request a discretionary budget in this application; to be used for the completion of open ATN studies, for the funding of new innovative pilot studies, for supporting collaboration or coendorsement agreements with other research networks, and for accommodating central protocol-mandated requirements (e.g., specimen processing costs) on an as-needed basis.

Requests for discretionary funds may not exceed $750,000 direct costs in the first year of the project period. Similar requests may be made in subsequent years of the project period. The application must describe the review procedures that will guide the Executive Committee in distributing discretionary funds.

•  Specific Application Requirements for Adolescent Medicine Data and Operations Center (DOC)

An application for the DOC is submitted by an institution on behalf of the Principal Investigator of the DOC who should propose an infrastructure and organizational support plan for the ATN in the application, clearly outlining the mechanisms proposed for staff and site training, site-specific subject accrual reimbursement, quality assurance procedures, the operation and integrity of the ATN study databases, ATN study development and support, and analytic capacity. These responsibilities should be presented with plans, processes, and timelines. It is important to note that funds for study protocols to be conducted by the individual Adolescent Medicine Trials Units (ATUs) will be awarded in the ATN DOC Notice of Grant Award (NGA) rather than each ATU NGA. The use of these funds will require prior approval from NICHD program and grants management; approval will release these funds for studies either in increments or full amounts for approved ATU protocols to the ATN DOC. The ATN DOC is responsible for the monitoring and distribution of protocol funds to the ATU as a fee for service arrangement. This mechanism will provide a centralized, equitable, and efficient method for coordinating the distribution of funds with actual subject accrual.

The DOC applicant should be able to respond flexibly to the changing needs of the ATN as the project unfolds, adding and deleting staff as the requirements dictate. The application should reflect an understanding of these processes. An application for the DOC 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 (the ATN uses remote data capture (RDC) and this capability must be maintained), management, analysis, and data quality control for internally-developed studies; and (3) plans for providing an electronic communication system to participants of the ATN.

The budget for the DOC should include, at a minimum, salary and administrative support for the PI, Project Director, and staff required to efficiently support open ATN studies as well as staff to support studies to be developed, and travel to two three-day ATN meetings per year.

The DOC budget should also include a funding request for Community Advisory Board (CAB) staff support and travel of CAB representatives (one from each ATU) to one annual meeting. Future year budgets may be escalated at 3 percent for recurring costs.

•  Specific Capacity-Based Application Requirements for Newly-Applying Adolescent Medicine Trials Unit (ATUs)

An application for an ATU is submitted by an institution on behalf of the Principal Investigator of the ATU who should present evidence of the following in the application:

(1) personal expertise, experience, and capacity to contribute to the implementation of the ATN research agenda as outlined in the duties of ATU PIs; (2) an interdisciplinary health team providing a wide array of adolescent-specific clinical services on site; (3) successful past research participation, with documentation of recruitment and retention rates; (4) the availability of experienced study coordinator(s); (5) clinic and health department numerical and rate data attesting to the presence of adolescents and youth between the ages of 12 and 24 years, with HIV infection rates or rates of high-risk behavioral activity in the clinic catchment's area; (6) ability to recruit and retain at least 75 HIV-positive youth and at least 125 HIV-negative but HIV-at-risk youth in the target age range; and (7) documentation of local CLIA-certified laboratory support.

Outreach plans and existing liaisons with other community organizations to access these youth should be described in detail, as well as documentation of past performance in these areas. Applications should describe the applicant's clinical research organization and should include plans, information, and documentation that describe the site's ability to accomplish the work successfully.

The budget for an ATU should include salary support for the Principal Investigator, study coordinator, outreach/recruiting worker, and support staff; all with appropriate justification. Local laboratory costs for open ATN studies will be negotiated with successful applicants prior to the award. Costs for travel to two two-day ATN meetings for the PI and primary study coordinator, communications, supplies, and equipment should be included. Future year budgets may be escalated at 3 percent for recurring costs. Funds for actual protocols should not be included in the application but will be negotiated at a later date on a per subject total cost basis. These funds will be managed and distributed to each participating ATU via the DOC as a fee for service arrangement after a protocol has been approved by the ATN and the NICHD has approved the funds for distribution. Applications should include a primary site only; consortium or sub-site arrangements will not be accepted and such applications will be considered non-responsive to the RFA. Multiple practice sites for research staff at the primary site are acceptable; future direct funding of these secondary sites is possible and will follow evidence of accrual to ATN studies.

•  Specific Performance-Based Application Requirements for Re-Competing Adolescent Medicine Trials Unit (ATUs)

An application for an ATU is submitted by an institution on behalf of the Principal Investigator of the ATU who should present evidence of the following in the application:

(1) the experience of the ATN staff in contributing to the development of the ATN research agenda through evidence of attendance at ATN meetings and conference calls, and service on protocol teams and committees; (2) the capacity of the site through a brief description of the site's interdisciplinary health team providing care and the array of adolescent-specific clinical services on site; (3) documentation of local CLIA certified laboratory support; and (4) the experience of the site in implementing the ATN research agenda. Related to this last requirement, it is the intention of NICHD to standardize the reporting of past performance in recruitment and retention of subjects to the ATN trials open to all sites. To achieve this, re-competing applicants should request the appropriate reporting tables from the NICHD program official listed below to include in the application. Applications from re-competing institutions will be considered non-responsive to the RFA if these tables are missing from the application.

The budget for an ATU should include salary support for the Principal Investigator, study coordinator(s), outreach/recruiting workers, and support staff; all with appropriate justification. Local laboratory costs for open ATN studies will be negotiated with successful applicants prior to the award. Costs for travel to two two-day ATN meetings for the PI and primary study coordinator, communications, supplies, and equipment should be included. Future year budgets may be escalated at 3 percent for recurring costs. Funds for actual protocols should not be included in the application but will be negotiated at a later date on a per subject total cost basis. These funds will be managed and distributed to each participating ATU via the DOC as a fee for service arrangement after a protocol has been approved by the ATN and the NICHD has approved the funds for distribution. Applications should include a primary site only; consortium or sub-site funding arrangements will not be accepted and such applications will be considered non-responsive to the RFA. Multiple practice sites for research staff at the primary site are acceptable; future direct funding of these secondary sites is possible and will follow evidence of enrollment into studies.

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible. The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

In submitting a plan, all applicants to the ACC component of the ATN should describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Applicants to all other organizational components need only note their intention to adhere to ATN policy; this will be considered responsive to the requirement to provide a data sharing plan.

Sharing Research Resources

Investigators responding to this funding opportunity should include a statement of intention to adhere to ATN policy for the storage and use of study biologic specimens in the ATN Repository.

Section V. Application Review Information

1. Criteria

Applications will be considered non-responsive to this solicitation if they fail to address all component-specific elements delineated in Section III.6. (Other Submission Requirements), above.

2. Review and Selection Process

Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by the NICHD. Incomplete and/or non-responsive applications will not be reviewed.

Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NICHD in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

3. Merit Review Criteria

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Specific Review Criteria for the ATN Coordinating Center (ACC)

1. Significance. Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

•  Adequacy of the proposed plans to address the intervention research agenda outlined in the most recent scientific plan of the Office of AIDS Research (http://www.nih.gov/od/oar/public/public.htm)

•  Adequacy and breadth of understanding of existing adolescent HIV-related research;

•  Adequacy and appropriateness of the proposed ranking of research priorities in the application;

•  Evidence that the proposed research agenda reflects the changing context of adolescent HIV infection in the United States.

2. Approach . Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

•  Adequacy of the plan for collaborative research and demonstration of current and proposed linkages with other research groups;

•  Strength and adequacy of the overall management plans, including plans for effective communication among ATN components and collaborators;

•  Adequacy of the plans for ATN policy enforcement and necessary policy revisions;

•  Adequacy of plans to assure the appropriate protection of the rights and safety of subjects involved in clinical investigations;

•  Adequacy of the review plans and procedures that will guide the Executive Committee in distributing discretionary funds.

3. Innovation . Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

•  Evidence that the research agenda addresses innovative approaches to the development and clinical evaluation of interventions in adolescents and youth.

4. Investigators. Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

•  Adequacy of qualifications, research experience, and time commitment of the AMLG PI;

•  Adequacy of the qualifications and research experience of the proposed scientific leadership, including previous experience or working knowledge of recent HIV adolescent-specific research findings;

•  Adequacy of the proposed resources and personnel for administering the ATN.

5. Environment. Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

Specific Review Criteria for Adolescent Medicine Data and Operations Center (DOC)

1. Significance. Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

•  Quality of the scientific contribution to the ATN research agenda;

•  Quality of the operational contribution to the ATN research agenda.

2. Approach. Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

•  Adequacy of site set-up and staff training plans;

•  Flexibility of plans to respond to the changing analytic needs of the ATN;

•  Adequacy of the plans to guarantee the quality and integrity of collected data;

•  Adequacy of plans to maintain accurate and timely information on the progress of studies and site performance.

3. Innovation. Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

•  Demonstration of innovative analytic approaches to evaluating clinical research data.

4. Investigators. Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

•  Adequacy of the qualifications and research experience of the management and analytic team;

•  Adequacy of previous experience with design, administration, management, and coordination of multi-center clinical studies or trials;

•  Adequacy of the proposed resources and personnel for supporting the ATN.

5. Environment. Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

Specific Review Criteria for Newly-Applying Adolescent Medicine Trials Unit (ATUs)

1. Significance. Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

•  Quality of the scientific contribution to the ATN research agenda;

•  Quality of the operational contribution to the ATN research agenda.

2. Approach. Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

•  Availability of the relevant populations for HIV intervention studies, including a demonstration of the site's capacity to recruit and retain at least 75 HIV-positive and at least 125 HIV-negative but HIV-at-risk youth in the target age range;

•  Strength and adequacy of plans and mechanisms for subject recruitment and retention, including plans to extend HIV testing and health care options to hard-to-reach youth populations (viz. run-away and throw-away youth, homeless and street youth, alcohol and drug-abusing populations) and plans to include both genders, minorities and their subgroups, and children as appropriate for the scientific goals of the research;

•  Strength and adequacy of the site's management and communication plan;

•  Adequacy of plans for implementing multiple intervention trials, including the ability to expand;

•  Adequacy of plans for community outreach and collaboration, as well as community representation in ATN research.

3. Innovation. Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

•  Evidence that the proposed contribution will provide innovative approaches to the identification, linkage to health care, and engagement in research of at-risk youth;

•  Evidence that the proposed plans will produce innovative strategies for recruiting and retaining youth in research studies.

4. Investigators. Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

•  Adequacy of professional qualifications and research experience of the PI;

•  Adequacy of the research experience of the PI and study coordinator in multi-center clinical research networks;

•  Adequacy of committee and analytic team experience of the PI in demonstrating an understanding of basic study design and data collection practices.

5. Environment. Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

•  Evidence of the required expertise, experience, and capacity to carry out the aims of the ATN research agenda;

•  Evidence of a well-established and -managed health care delivery system provided by a multidisciplinary care team with the full scope of adolescent-specific services available on-site;

•  Evidence that the clinical settings for adolescents and youth have a comfortable, drop-in atmosphere with attention to group and individual counseling and support.

Specific Review Criteria for Re-competing Adolescent Medicine Trials Unit (ATUs)

1. Significance. Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

•  Quality of the scientific contribution to the ATN research agenda;

•  Quality of the operational contribution to the ATN research agenda.

2. Approach. Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

•  Demonstration of past ability to recruit and retain subjects in ATN studies through an examination of performance tables;

•  Evidence that past plans resulted in mechanisms for subject recruitment and retention, including any plans that extended HIV testing and health care options to hard-to-reach youth populations (viz. run-away and throw-away youth, homeless and street youth, alcohol and drug abusing populations);

•  Strength and adequacy of the site's management and communication plan;

•  Adequacy of plans for implementing multiple intervention trials, including the ability to expand;

•  Evidence that past plans resulted in community outreach and collaboration, as well as community representation in ATN research

3. Innovation. Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

•  Evidence that the past contribution has provided innovative approaches to the identification, linkage to health care, and engagement in research of at-risk youth;

•  Evidence that the past plans have produced innovative strategies for recruiting and retaining youth in research studies.

4. Investigators. Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

•  Adequacy of professional qualifications and research experience of the PI;

•  Adequacy of the research experience of the PI and study coordinator in multi-center clinical research networks;

•  Adequacy of committee and analytic team experience of the PI in demonstrating an understanding of basic study design and data collection practices.

5. Environment. Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

•  Evidence of the required expertise, experience, and capacity to carry out the aims of the ATN research agenda;

•  Evidence of a well-established and -managed health care delivery system provided by a multidisciplinary care team with the full scope of adolescent-specific services available on-site;

•  Evidence that the clinical settings for adolescents and youth have a comfortable, drop-in atmosphere with attention to group and individual counseling and support.

3.A. Additional Review Criteria

In addition to the above criteria, the following items will be considered in the determination of scientific merit and the priority score:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

3.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

3.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.

3.D. Sharing Research Resources
Not Applicable

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the Principal Investigator will also receive a written critique called a summary statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm

A formal notification in the form of a Notice of award will be provided to the applicant organization. The notice of award signed by the grants management officer is the authorizing document.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NGA (Notice of Grant Award) are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Once all administrative and programmatic issues have been resolved, the Notice of Grant Award will be generated via e-mail notification from the awarding component, NICHD, to the grantee business official (designated in Item 14 on the Application Face Page). If a grantee is not e-mail enabled, a hard copy of the Notice of Grant Award will be mailed to the business official.

2. Administrative Requirements

All awardees are required to submit annual progress reports to the co-sponsoring Institutes providing study and site performance information as stipulated by the institutes and to respond to and address performance issues identified during the budget year.

All NIH Grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the notice of grant award. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.


2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement (U 01 ), 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 above.

2.A.1. Principal Investigator Rights and Responsibilities

o Adolescent Medicine Coordinating Center (ACC)

The ACC consists of the Principal Investigator, Project Director, and supporting staff of the institution receiving the award for the AMLG. The duties of the ACC include, but are not limited to, the following:

•  Provide for effective communication within the ATN; disseminating information, coordinating conference calls, and collaboratively setting meeting and call agendas;

•  Review and maintain all current ATN 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;

•  Execute all Memoranda of Understanding or Agreement with other entities to conduct ATN developed or co-endorsed research;

•  Record and archive all EC-directed ATN group meeting and conference call minutes and all ATN study developmental documents;

•  Maintain the ATN discretionary fund and execute all necessary subcontracts or agreements to support ATN function and research with NICHD approval;

o Adolescent Medicine Leadership Group (AMLG)

The AMLG will consist of the Principal Investigator of the ATN Coordinating Center (ACC) and ATN Data and Operations Center (DOC), the project directors of the ACC and DOC, the collaborating investigators comprising the AMLG subgroups, and the NIH project scientists. The Principal Investigator of the ACC will serve as chair of the group. A vice-chair will be elected by the members and from among the members of each leadership subgroup. The ACC project director will coordinate the activities of the AMLG at the direction of its officers. The AMLG will have the primary responsibility for defining the research agenda and its implementation in the network, and initiating and maintaining collaboration with other NIH-funded HIV-related research networks within the guidelines of this RFA. The AMLG 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 HHS, PHS, and NIH policies.

Specifically, the AMLG will:

•  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 submit to the ATN Executive Committee for approval;

•  Retain the primary responsibility for defining and prioritizing the research agenda and submitting the agenda to the ATN Executive Committee for approval;

•  Evaluate all ATN-sponsored research studies from the previous project period for the ethics, feasibility, and utility of their continuation;

•  Identify the most efficient and scientifically sound mechanisms for developing the research agenda, deciding if the specific agenda items are best pursued independently in the ATN, given resources, or in collaboration with existing research networks;

•  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 the ATU Principal Investigators, addressing their scientific and medical interests and the capacity of their sites;

•  Coordinate ATN collaboration with investigators with funding from sources other than NIH-funded networks. These investigators may include, but are not limited to, individuals with RO1 funding;

•  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;

•  Develop in collaboration with the leadership of NIH-supported or other prevention and clinical trials networks formal liaison mechanisms to facilitate interaction and communication on an ongoing basis for the purpose of early involvement in protocol design to address the key scientific and clinical questions in the adolescent population per se or in populations which include adolescents;

•  Consult and interact with NIH-supported or other prevention and clinical trials networks in the design or adaptation of existing trials to meet the needs and characteristics of adolescent populations in order to implement these trials in subjects available in the ATN;

•  Assume responsibility for communication and liaison with existing networks to inform scientific working group chairs of the issues which the ATN would like to see pursued in clinical, behavioral, and prevention research; negotiate shared study costs; and to define and resolve key logistical issues (e.g. data collection and transfer, drug repository and regulatory requirements) which must be addressed to facilitate adolescent enrollment in collaboratively developed research protocols;

•  Recommend the implementation of independent or collaborative research to the Executive Committee when two-thirds of the AMLG subgroup members approve the research concept and the remaining AMLG members confirm;

•  Identify, with the assistance of the NICHD staff, resources within the ATN to support subject recruitment, enrollment, retention, data collection, specimen shipping, and negotiated protocol monitoring costs for ATN-approved protocols and recommend to NICHD the use of funds for such support;

•  Negotiate any ATN rights to data and authorship with executive bodies of collaborating networks;

•  Participate in regular conference calls and attend AMLG meetings to be held at least semi-annually.

o Data and Operations Center

The Data and Operations Center (DOC) will consist of the Principal Investigator, DOC project director, and staff deemed necessary to carry out the mission of the DOC. The DOC project director will coordinate the activities of the DOC at the direction of the principal investigator.

The DOC will:

•  Maintain the ATN protocol disbursement fund and execute all necessary agreements with ATUs to support study and subject accrual costs reconciling reimbursement to site performance with NICHD approval;

•  Collaboratively plan and conduct all AMLG and ATN meetings;

•  Provide methodologic and analytic support to 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;

•  Supervise all data collection procedures by the ATUs, arranging for combined efforts when indicated by regulatory demands of collaborative research;

•  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 at the ATUs;

•  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) when instructed by NICHD;

•  Provide training, including the development and updating of study manuals of operation, to all ATU site personnel related to acceptable quality control and quality assurance procedures at the sites as well as protocol-training where indicated;

•  Provide on-site monitoring to the ATUs for those studies being performed at a particular site on a schedule dictated by the EC or its authorized subcommittee;

•  Recruit and support the Community Advisory Board (CAB) staff person who will act as a liaison between the CAB members and the ATN, and provide logistical support to any CAB-associated meetings;

•  Participate in regular conference calls and attend AMLG meetings to be held at least semi-annually.

o The Adolescent Medicine Trials Principal Investigators (ATP) Group

The ATP Group will consist of the Principal Investigators of the ATN-funded sites. The ATP Group will have a chair and vice chair elected from among and by the ATP Principal Investigators.

Specifically, the ATP Group will:

•  Have primary responsibility for the implementation of ATN-approved study protocols, where feasible, the recruitment and monitoring of study participants, associated data collection, and study-associated quality control measures at the clinical site including but not limited to identifying local CLIA-certified laboratory support in facilities participating in NIAID-supported quality assurance programs when indicated; these activities may be coordinated by the site study coordinator at the direction of the Principal Investigator;

•  Obtain Institutional Review Board (IRB) approval of all ATN study protocols implemented locally and comply with both IRB and ATN policies and procedures;

•  Provide counsel and advice to the ATN Executive Committee through its elected representatives on the feasibility of proposed research, implementation strategies, and subsequent data collection as well as information on their own perceptions of needed intervention evaluations;

•  Recruit at least one youth per site to serve as a community representative, who shall be between the ages of 16 and 21 at the time of recruitment, to participate in the ATN Community Advisory Board;

•  With consultation from the Study Coordinators Group, formulate the format and procedures for input to the ATN from the Community Advisory Board;

•  Have the opportunity to generate, either unilaterally or in collaboration with ATP investigators, clinical research proposals for submission to the AMLG for review;

•  Participate in conference calls and attend ATN meetings to be held at least semi-annually.

2.A.2. NIH Responsibilities

An NIH Project Scientist will 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 RFA.

The NIH Project Scientists will:

•  Facilitate the exchange of information between the AMLG and other existing research networks to support collaborative efforts;

•  Participate in the Executive Committee that oversees the establishment and maintenance of the ATN and its progress in achieving program goals;

•  Assist the Executive Committee 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 AMLG in the selection of research topics, and the development or review of protocols for specific studies and interventions;

•  Arrange program review of all ATN protocols and, when necessary, the external peer review of the protocols, clearing these studies for implementation;

•  Assist the AMLG in identifying ATN resources required for the successful implementation of collaboratively developed research protocols;

•  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 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.

2.A.3. Collaborative Responsibilities

The Executive Committee

The Executive Committee is the main governing body of the ATN. The Committee is composed of the Chair of the AMLG, the Vice Chair(s) of the AMLG subgroups, and Project Director of ACC; the Principal Investigator and Project Director of the DOC; the Chair and Vice Chair of the ATP Group; and the NICHD project scientist. Other NIH project scientists are non-voting members. The Chair(s) and Vice Chair(s) of ancillary study groups and the CAB Staff Person are non-voting and ad hoc members of the Executive Committee. A quorum must exist for Executive Committee action; a quorum consists of five voting members. Voting members will have one vote each, and motions will carry with a simple majority. The Chair of the AMLG will also chair the Executive Committee. The Vice Chair of the Executive Committee will be elected by the entire committee from among the committee members; none of the NIH project scientists are eligible to serve as Chair or Vice Chair of the Executive Committee.

The Executive Committee will:

•  Assist the AMLG in the identification of adolescent HIV/AIDS research issues;

•  Approve the direction of the research effort including any reconfiguration of the research subgroups to better address the direction of the scientific agenda, and oversee the conduct and monitoring of the studies;

•  Approve the ATN policies and procedures adopted, revised, or developed by the AMLG;

•  Implement and enforce, either directly or through delegation to other ATN-supported personnel, a Conflict of Interest (COI) Policy acceptable to the Pediatric, Adolescent, and Maternal AIDS 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 COI 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;

•  Approve the research agenda specific to its feasibility, clinical relevance, and implications as well as advise on the development of implementation strategies;

•  Approve use of discretionary funds as recommended by the AMLG;

•  Establish timelines for the completion of tasks and monitor progress;

•  Oversee site participation and performance, informing the appropriate program managers.

Each full member will have one vote. Awardee members of the Executive Committee will be required to accept and implement policies approved by the Executive Committee.

2.A.4. Arbitration Process

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 arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the Executive 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 arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Award Criteria

The following will be considered in making funding decisions:

4. Reporting

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually:
http://grants.nih.gov/grants/funding/2590/2590.htm and financial statements as required in the NIH Grants Policy Statement.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

Audrey Smith Rogers , Ph.D., M.P.H.
Pediatric, Adolescent and Maternal AIDS Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard , Room 4B11, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 435-6873
FAX: (301) 496-8678
Email: Audrey.rogers@nih.hhs.gov

Nicolette Borek, Ph.D.
Behavioral and Brain Development Branch
Division of Clinical Neuroscience, Development, and Behavioral Treatment
National Institute on Drug Abuse
6001 Executive Boulevard, Room 5198, MSC 9593
Bethesda, MD 20892-9593
Telephone: (301) 402-0866
FAX: (301) 443-6814
Email: nborek@nida.nih.gov

Andrew D. Forsyth, Ph.D.
Chief, Primary HIV Prevention and Behavior Change Program
Division of AIDS and Health and Behavior Research
National Institute of Mental Health
6001 Executive Boulevard, Room 6201, MSC 9619
Bethesda, MD 20892-9616
Telephone: (301) 443-8403
FAX: (301) 443-9719
Email: Andrew.forsyth@nih.hhs.gov

2. Peer Review Contacts:

Robert Stretch, Ph.D.
Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard Room 5B01, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 496-1485
FAX: (301) 402-4104
Email: stetchr@mail.nih.gov


3. Financial or Grants Management Contacts:

Lisa Moeller
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard Room 8A01, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 435-6995
FAX: (301) 451-5510
Email: lisa.moeller@nih.hhs.gov

Section VIII. Other Information

Required Federal Citations

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained. http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm.

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity, and dose-finding studies (phase I); efficacy studies (Phase II) efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible. http://grants.nih.gov/grants/policy/data_sharing.

Investigators should seek guidance from their institutions, on issues related to institutional policies, local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research ( http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects that is available at http://grants.nih.gov/grants/funding/children/children.htm.

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Public Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this PA in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. 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 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.


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