ADOLESCENT MEDICINE TRIALS NETWORK FOR HIV/AIDS INTERVENTIONS

Release Date:  February 14, 2000

RFA:  HD-00-002 (Reissued, see RFA-HD-04-025)

National Institute of Child Health and Human Development 
National Institute on Alcohol Abuse and Alcoholism
National Institute on Drug Abuse
National Institute of Mental Health


Pre-Application Conference:     March 25, 2000
Letter of Intent Receipt Date:  April 15, 2000 
Application Receipt Date:       July 11, 2000

PURPOSE 

The Adolescent Medicine HIV/AIDS Research Network (1994-2001) has been the 
only national study of the emerging epidemic in teens infected through sex or 
injecting-drug behaviors.  The information derived from this network will be 
able to inform the nation’s adolescent-specific HIV/AIDS scientific agenda to 
improve the prevention of HIV infection and the medical treatment of HIV-
positive teens.  The National Institute of Child Health and Human Development 
(NICHD), in partnership with the National Institute on Alcohol Abuse and 
Alcoholism (NIAAA), the National Institute on Drug Abuse (NIDA), and the 
National Institute of Mental Health (NIMH), now intends to support a research 
network infrastructure with the capacity for behavioral, microbicidal, 
prophylactic, therapeutic, and vaccine trials to take full advantage of the 
results of the detailed observational and laboratory-intensive studies of the 
Adolescent Medicine HIV/AIDS Research Network.

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 such as the HIV Prevention 
Trials Network (HPTN), HIV Vaccine Trials Network (HVTN), the Pediatric and 
Adult AIDS Clinical Trials Groups (PACTG, AACTG), the Community Programs for 
Clinical Research on AIDS (CPCRA), and others, on promising behavioral, 
microbicidal, prophylactic, therapeutic, and vaccine modalities in HIV-
infected and HIV-at-risk adolescents, ages 12 through 24 years.  

It is anticipated that 25 percent or less of the ATN research will be 
generated independently, with the remainder conducted in collaboration with 
other existing networks.  The 25 percent independent, internal ATN research 
activities are expected to focus on short-term studies (e.g., pathogenic 
mechanisms, pilot or feasibility studies) in order to generate preliminary 
data in support of collaborative protocol development either with NIH-funded 
research networks or independent investigators through RO1 funding mechanisms.  
Seventy-five percent of the research activities of the ATN will focus on 
collaboration with other networks or investigators to implement the ATN 
research agenda.  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.  For 
the purposes of collaborative research, ATN resources will support the site-
specific and negotiated subject-specific costs entailed in collaborative 
research activities, and will not duplicate but draw upon the regulatory, drug 
repository, laboratory, forms design, database management, and statistical 
capacity available in the NIH-funded research networks that choose to 
collaborate with the ATN. 

HEALTHY PEOPLE 2010 

The Public Health Service (PHS) is committed to achieving the health promotion 
and disease prevention objectives of "Healthy People 2000," a PHS-led national 
activity for setting priority areas.  This Request for Applications (RFA) is 
related to one or more of the priority areas.  Potential applicants may obtain 
"Healthy People 2010" at http://odphp.osophs.dhhs.gov/pubs/hp2000/.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic for-profit and non-profit 
organizations, public and private, such as universities, colleges, hospitals, 
laboratories, units of State and local governments, and eligible agencies of 
the Federal government.  Foreign institutions are not eligible to apply for 
these grants.  Racial/ethnic minority individuals, women, and persons with 
disabilities are encouraged to apply as Principal Investigators.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) cooperative research 
project grant  (UO1) mechanism.  The U01 is a cooperative agreement, an 
"assistance" mechanism (rather than an "acquisition" mechanism) in which 
substantial NIH scientific and/or programmatic involvement with the awardee is 
anticipated during the performance of the activity.  Under the cooperative 
agreement, the NIH purpose is to support and/or stimulate the recipient's 
activity by involvement in and otherwise working jointly with the award 
recipient in a partner role, but it is not to assume direction, prime 
responsibility, or a dominant role in the activity.  Consistent with this 
concept, the dominant role and prime responsibility for the activity reside 
with the awardees for the project as a whole, although specific tasks and 
activities in carrying out the studies will be shared among awardees and the 
NIH staff collaborators.

FUNDS AVAILABLE

The NICHD intends to commit approximately $5.8 million, the NIDA approximately 
$750,000, the NIMH approximately $350,000, and the NIAAA approximately 
$300,000 in total costs (including direct and facilities and administrative 
costs) in FY 2001 to fund one leadership group grant, one data and operations 
center grant, and 18-20 trials unit grants in response to this RFA.  An 
applicant for the leadership group may request a project period of up to five 
years and a budget for direct costs of up to $775,000 in the first year, 
excluding indirect costs on consortium arrangements, and including 
discretionary funds of $250,000.  An applicant for the data and operations 
center may request a project period of up to five years and a budget for 
direct costs of up to $450,000 in the first year, excluding indirect costs on 
consortium arrangements.  An applicant for a trials unit may request a project 
period of up to five years and a budget for direct costs of up to $120,000 in 
the first year. 

Although the financial plans of the NICHD, NIAAA, 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.  At this time, it is not known if this RFA will be reissued.

RESEARCH OBJECTIVES

Background

Cases of HIV infection continue to rise in adolescents and young adults.  
There were 586 cases in 13-19 year olds and 1,605 cases in 20-24 year olds 
reported to the Centers for Disease Control and Prevention (CDC) in 1997 by 
those states reporting HIV infection.  One year later, new HIV diagnoses 
reported in these two age categories were 727 and 1,999, respectively.  In the 
13-19 year old group, 62 percent were female; and in the 20-24 year old group, 
43 percent were female. The majority of all reported new HIV infections are in 
minority populations; 62 percent in the 13-24 age group are of African 
American or Hispanic origin.  The primary transmission for reported AIDS cases 
has always been sexual in adolescent females and became predominantly 
male-to-male sexual transmission in adolescent males in 1995.  Thus, the 
picture of the expanding adolescent HIV epidemic based on incident reports to 
the CDC is one that is increasingly female, minority, and sexually-transmitted 
through heterosexual activity in females and homosexual activity in males.  At 
the same time, increasing numbers of children who had been infected 
perinatally are surviving to adolescence. 

Clinical research for HIV-infected youth has been hampered by the 
disproportionately small number of the estimated HIV-seropositive youth who 
are identified and successfully linked to health care.  Consequently, there 
exists no broad-based clinical research infrastructure for HIV-infected 
adolescents with their particular challenges and unique management demands 
that is comparable to those established to address adult and pediatric 
HIV-infected populations. 
Behavioral interventions that incorporate adolescent-specific skill-building 
programs that take into account differing levels of adolescent cognitive 
functioning need to be tested.  Primary prevention efforts that combine STI 
(sexually-transmitted infection) treatment-, barrier method-, and microbicide- 
approaches specific to adolescents need to be explored.  Additional work is 
needed on understanding the maturation of the mucosal immune response in 
adolescents to inform mucosal vaccine development. 

In anticipation of the availability of a preventive HIV vaccine, preparedness 
studies examining acceptability and feasibility of a preventive HIV vaccine 
initiative are required.  Such studies also should explore the unique ethical 
considerations inherent in vaccine program implementation, particularly in 
disenfranchised or emancipated youth.  HIV-infected youth now are appearing in 
health care in increasing numbers so the timing is right for assessing why and 
how prior prevention strategies and programs failed.  Studying the particular 
constellation of risk that led to HIV infection in seropositive adolescents 
may produce insights into targeting strategies toward subpopulations at 
increased risk.  Further study also is required into what factors constituted 
barriers to the effective utilization of preventive programs in the 
already-infected population.

Information on the manifestation and progression of HIV disease, critical to 
the development and evaluation of a therapeutic agenda, has been established. 
The effect of early, aggressive therapy needs to be studied, as well as 
additional inquiry into the full immunologic potential of adolescents and 
methods for enhancing their HIV-specific cellular immune response. 
Alternatively, study is required into the effect of delaying treatment when 
clinical parameters exhibit no apparent damage and the probability of drug 
adherence is low.  Special attention is needed for perinatally-infected 
adolescents who experience all of the sociobehavioral difficulties of their 
sexually-infected peers, but also face unique clinical management problems 
given multiple drug regimen failures in their treatment past.

All HIV-infected youth are faced with the social and physical developmental 
challenges of puberty which make coming to terms with chronic illness, complex 
drug regimens, and disclosure to peers an intensely more complicated endeavor.  
The consequences of HIV infection for adolescents is a profoundly understudied 
area demanding attention.  There are few adolescent-specific studies to 
develop strategies to improve treatment adherence, and to prevent or minimize 
the negative physical, psychological, cognitive, and social consequences of 
HIV infection, particularly during the critical developmental periods of 
adolescence. 

The manifestations of HIV infection in both vertically and horizontally 
infected adolescents need to be evaluated specific to HIV pathogenesis, the 
potential for immune recovery, and the effect of HIV on pubertal development.  
The long-term consequences of the newer drug therapies with demonstrated 
metabolic effects administered to adolescents during periods of pronounced 
growth and sexual maturation also are unknown and require study.  As these 
more effective antiretroviral agents are used more widely in youth, the 
resulting improved survival may permit the emergence of HIV-induced 
malignancies, particularly those resulting from co-infection with human 
papillomavirus (HPV) or Hepatitis B (HBV). 

Scope of Research

This initiative calls for a broad array of supporting and direct intervention 
studies aimed at the primary, secondary, and tertiary prevention of HIV 
infection in adolescents and young adults at each trials unit in the network. 
The application should present an implementation plan to address the research 
objectives outlined in the 1999 Office of AIDS Research Report on NIH-
sponsored Pediatric and Adolescent HIV Infection Research  
(http://www.nih.gov/od/oar/public/public.htm).  Primary prevention studies 
address behavioral, physical, and/or chemical efforts to interrupt HIV 
transmission in uninfected populations.  These include, but are not limited 
to, interventions focused on one or more of the following modalities: 

o  assessment of acceptability and feasibility of preventive vaccine 
initiatives in adolescent and young adults;

o  evaluation of models of disseminating HIV prevention information and access 
to health care;

o  adolescent-specific skill-building efforts related to responsible sexual 
relationships, avoidance of alcohol and substance abuse, effective condom use, 
and microbicide use;  

Secondary prevention studies examine behavioral, nutritional, and/or 
pharmacologic/therapeutic interventions in order to preserve health in HIV-
infected populations.  These include, but are not limited to: 

o  evaluation of community methods of identifying HIV-positive youth and 
linking them to health care;

o  clinical evaluation of therapies to exploit the immunologic resilience of 
recently-infected youth;

o  clinical trials to study both the efficacy and long-term safety of current 
and new antiretroviral agents;

o  management trials to study newer drug schedules in order to simplify 
regimens;

o  the evaluation of programs designed to promote antiretroviral drug 
adherence in youth. 

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:
 
o  the effective management of adolescents presenting very ill, as well as the 
management of adolescents with dwindling therapeutic options;

o  the assessment of the impact of both HIV infection and its therapy on the 
life-decisions of young adults with respect to relationships, education, 
employment, and child-bearing with the development of theory-based 
interventions. 

Studies on all three levels should be multidisciplinary collaborations to 
address the complexity of the population.

Organizational Components

The Adolescent Medicine Trials Network (ATN) for HIV/AIDS Interventions will 
consist of the Adolescent Medicine Leadership Group (AMLG), a Data and 
Operations Center (DOC), and Adolescent Medicine Trials Units (AMTUs).  
Ancillary groups include the Study Coordinator Group and the Community 
Advisory Board.  Governance and coordination will be provided by an Executive 
Committee, comprising the Principal Investigator and Chair, the Vice Chair, 
and  the Project Director of the AMLG, the Principal Investigator and Project 
Director of the DOC, the Chair and Vice Chair representatives elected by and 
from among the Principal Investigators of the AMTUs, and the NICHD staff 
science collaborator. (Other NIH staff science collaborators will serve as 
non-voting members of the Executive Committee, and two representatives of the 
study coordinators at the AMTUs and the staff person of the Community Advisory 
Board may serve as non-voting ad hoc members.)
Research Responsibilities

The Principal Investigator (PI) of the Adolescent Medicine Leadership Group 
(AMLG) is responsible for assembling the necessary multidisciplinary team of 
established investigators from within and outside of the PI’s home institution 
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, microbicidal, prophylactic, therapeutic, and vaccine trials).  The 
AMLG establishes and maintains collaborative relationships with other research 
networks in order to implement the full research agenda.

The Adolescent Medicine Data and Operations Center (DOC) has the 
responsibility to provide the ATN’s infrastructure and organizational support, 
staff and site training, quality assurance procedures, the operation and 
integrity of the managerial database, ATN study development and support, and 
analytic capacity. 

The Adolescent Medicine Trials Units (AMTUs) 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 AMTUs enroll and monitor subjects in a central managerial 
database, and provide guidance and counsel on the acceptability and 
feasibility of proposed network research.

SPECIAL REQUIREMENTS

Special Application Requirements for each organizational component (the 
Adolescent Medicine Leadership Group, the Data and Operations Center, and the 
Adolescent Medicine Trials Units) are provided under APPLICATION PROCEDURES.

Terms and Conditions of Award

The following terms and conditions will be incorporated into the award 
statement and provided to each Principal Investigator as well as the 
institutional officials at the time of the award.  These terms are in addition 
to, and not in lieu of, otherwise applicable OMB administrative guidelines, 
HHS Grant Administration Regulations at 45 CFR Part 74 and 92, and other HHS 
and NIH grant administration policies.  Business management aspects of these 
awards will be administered by the NICHD Grants Management Office in 
accordance with HHS and NIH Grant Administration policies. It is envisioned at 
this time that all awarded funds will be administered by the NICHD Grants 
Management Office.

The cooperative agreement funding mechanism will require collaboration among 
the NICHD representative(s), the Leadership Group Principal Investigator, the 
Data and Operations Center Principal Investigator, and the Principal 
Investigators of the Trials Units.  NICHD will assist in coordinating the 
activities of the ATN as defined below and will facilitate the exchange of 
information.

1. The Primary Rights and Responsibilities of the Awardees are as follows:

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.

o  Adolescent Medicine Leadership Group (AMLG) 

The AMLG will consist of the Principal Investigator, the AMLG project 
director, and the collaborating investigators identified in the successful 
application, and the NIH staff science collaborators.  The Principal 
Investigator of the AMLG will serve as chair of the group. A vice-chair will 
be elected by the AMLG. The AMLG 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.  Specifically, the AMLG will:

Devise 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;

Provide for effective communication within the ATN;

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

Evaluate 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;

Specify the required elements of the managerial database and collaborate with 
the DOC in managerial database design; subjects will be recruited into the 
network on the basis of willingness to consider trial participation and a 
simple managerial database will permit immediate calculation of available and 
eligible subjects for any study proposed for implementation in the network;

Commit to the development of preventive and therapeutic adolescent-focused 
studies that take into account the needs and capacities of this special youth 
population, and the scientific and medical interests and capabilities of the 
AMTU Principal Investigators;

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;

Contact the leadership of NIH-supported or other prevention and clinical 
trials networks, including but not limited to the Adult and Pediatric AIDS 
Clinical Trials Groups, the HIV Prevention Trials Network, and the HIV Vaccine 
Trials Network, to inform them of the ATN’s goals, objectives, and 
organizational structure; 

Develop in collaboration with these leadership groups 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 members approve the research 
concept;

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;

Retain custody of and have primary rights to the data developed from 
independent research under these awards, during the life of the award and two 
years subsequent to its termination, subject to government rights of access 
consistent with current HHS and NIH policies;

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:

Collaboratively plan and conduct AMLG and ATN meetings;

Interact with the AMLG on managerial database design and monitoring issues;

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 AMTUs, 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 AMTUs; 

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

Provide periodic on-site monitoring to the AMTUs for those studies being 
performed at a particular site;

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 Unit (AMTU) Group

The AMTU Group will consist of the Principal Investigators of the AMTU grants, 
awarded on the basis of past accomplishment in conducting adolescent clinical 
research and future capacity to participate effectively in implementing ATN 
study protocols.  The AMTU Group will have a chair and vice chair elected from 
among and by the AMTU Principal Investigators.  Specifically, the AMTU 
Principal Investigators will:

Have primary responsibility for the implementation of the ATN managerial 
database and 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; 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 two youths to serve as community representatives, one as the primary 
representative and the other as an alternate, who both shall be between the 
ages of 16 and 21 at the time of recruitment and 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 
AMLG 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. NIH Staff Science Collaborator Involvement

Staff Science Collaborators will represent each of the institutes co-
sponsoring the RFA.  The science collaborators 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, when necessary, for 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.

3.  Collaborative Responsibilities: The Executive Committee

The Executive Committee is the main governing body of the ATN.  The Committee 
is composed of the Chair, Vice Chair, and Project Director of the AMLG; the 
Principal Investigator and Project Director of the DOC; the Chair and Vice 
Chair of the AMTU Group; and the NICHD staff science collaborator.  Other NIH 
science collaborators are non-voting members.  The Chair and Vice Chair of the 
Study Coordinators Group 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 science collaborators 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, and facilitate the conduct and 
monitoring of the studies;

Approve the ATN policies and procedures developed by the AMLG;

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.

4. Arbitration Process

The specific terms and conditions above and the details of arbitration 
procedures below pertaining to the scope and nature of the interaction among 
NIH and participating sites will be incorporated into the notice of grant 
award.  These procedures will be in addition to the customary programmatic and 
financial negotiations that occur in the administration of grants. Arbitration 
procedures will be invoked only when agreement cannot be reached on 
programmatic issues that may arise between awardee(s) and the science 
collaborator(s) after the award has been made.  In that event, an arbitration 
panel will be composed of three members-- one selected by the Executive 
Committee (with the NICHD science collaborator not voting) or by the 
individual awardee in the event of an individual disagreement, a second member 
selected by the NIH  program officers, and a third member selected by the two 
prior selected members.  The decision of the arbitration panel by majority 
vote will be binding.  This special arbitration procedure in no way affects 
the awardee's right to appeal an adverse action that is otherwise appealable 
in accordance with the PHS Regulations at 42 CFR Part 50, Subpart D and HHS 
Regulation at 45 CFR Part 16.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and 
their subpopulations must be included in all NIH-supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification are provided 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 research involving human subjects should read the 
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research," which was published in the Federal Register of March 28, 1994 (FR 
59 14508-14513) and in the NIH Guide for Grants and Contracts, Vol. 23, No. 
11, March 18, 1994, and is available at:  
http://grants.nih.gov/grants/guide/notice-files/not94-100.html. 

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of NIH that children (i.e., individuals under the age of 21) 
must be included in all human subjects research, conducted or supported by the 
NIH, unless there are scientific and ethical reasons not to include them.  
This policy applies to all initial (Type 1) applications submitted for receipt 
dates after October 1, 1998.

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 was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available at: 
http://grants.nih.gov/grants/guide/notice-files/not98-024.html.

Investigators also may obtain copies of these policies from the program staff 
listed under INQUIRIES.  Program staff may also provide additional relevant 
information concerning the policy.

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes a 
descriptive title of the proposed research, the name, address, and telephone 
number of the Principal Investigator, the identities of other key personnel 
and participating institutions, and the number and title of this RFA.  
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 NICHD staff to estimate the potential review workload and 
avoid conflict of interest in the review.

The letter of intent is to be sent to Dr. Audrey Smith Rogers at the address 
listed under INQUIRIES, below, by April 15, 2000.

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be used in 
applying for these grants.  These forms are available at most institutional 
offices of sponsored research, on the web at 
http://grants.nih.gov/grants/funding/phs398/phs398.html and from the Division 
of Extramural Outreach and Information Resources, National Institutes of 
Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 
(301) 435-0714, E-mail:  Grantsinfo@nih.gov. 

Application Preparation

All instructions accompanying Form 398 (rev. 4/98) should be followed, except 
for those items modified by the following special instructions:

On line 2 of the face page of the application, applications must clearly 
indicate the component applied for, specifying either “Adolescent Medicine 
Leadership Group” or “Adolescent Medicine Data and Operations Center” or 
“Adolescent Medicine Trials Unit.”  If an institution intends to apply for 
more than one component of the Adolescent Medicine Trials Network for HIV/AIDS 
Interventions, the institution must submit a separate application for each 
component.

The names of key personnel involved in each application, regardless of whether 
salary support is requested, should be listed on Form Page 2 of the 
application and described in the narrative Budget Justification, with their 
specific responsibilities in support of the research effort outlined and 
percent time specified.  Alphabetized Biographical Sketches for key personnel 
(limited to two pages each) should follow the budget justification.

o  Specific Application Requirements for Adolescent Medicine Leadership Group 
(AMLG)

An application for the AMLG is submitted by an institution on behalf of the 
Principal Investigator of the AMLG 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 required to be represented on the AMLG include HIV 
virology, immunology, mucosal immunology, endocrinology, adolescent medicine, 
and adolescent behavior.  Other disciplines should be included as required to 
support the proposed research agenda (e.g., infectious disease, gynecology, 
pharmacology).  The proposed research agenda should address the full spectrum 
of trials listed in the NICHD’s purpose for establishing the ATN (viz. 
behavioral, microbicidal, prophylactic, therapeutic, and vaccine trials).

Evidence of potential collaborative relationships with existing research 
networks should be provided.  Applicants are encouraged to consider, in 
particular, relationships with research networks such as the Prevention Trials 
Network (PTN), Vaccine Trials Network (VTN), the Pediatric and Adult AIDS 
Clinical Trials Groups (PACTG, AACTG), and the Community Programs for Clinical 
Research on AIDS (CPCRA).

The budget for the AMLG should include, at a minimum, salary and 
administrative support for the AMLG and the committees of the ATN, and travel 
to one three-day AMLG meeting and two three-day ATN meetings per year.

The AMLG PI should also request a discretionary budget in this application; 
one-quarter to be used for funding innovative pilot studies, and supplementing 
the budgets of collaborating institutions undertaking resource-intensive pilot 
studies, and three-quarters in reserve to accommodate non-routine, protocol-
mandated requirements (e.g., specimen shipping costs) on an as-needed basis.  
Requests for discretionary funds may not exceed $250,000 direct costs in the 
first year of the study.  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.

o  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, quality assurance 
procedures, the operation and integrity of the managerial database, ATN study 
development and support, and analytic capacity.  These responsibilities should 
be presented with plans, processes, and timelines.  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 managerial database design and administration; (2) plans for data 
collection, management, analysis, and data quality control for internal pilot 
studies; and (3) plans for providing an electronic mail 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 for first study year 
responsibilities (managerial database and AMTU training and set-up), and 
travel to one three-day AMLG meeting and 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 
AMTU) to one annual meeting.

o  Specific Application Requirements for Adolescent Medicine Trials Unit 
(AMTUs)

An application for an AMTU is submitted by an institution on behalf of the 
Principal Investigator of the AMTU 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 AMTU 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 area; and (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. 

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 AMTU 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 the 
managerial database elements and screening costs for intervention trial 
participation should be included.  Costs for travel to two two-day ATN 
meetings for the PI and primary study coordinator, communications, supplies, 
equipment, and subject reimbursement and compensation should be included.

Submission Procedures

The RFA label available in the PHS 398 (rev. 4/98) application form must be 
attached to the bottom of the face page of the application and must display 
the RFA number HD-00-002.   A sample RFA label is available at:  
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.  Please note that 
this is in pdf format.  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.

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
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, two additional copies of the application should be 
sent to:

Director
Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5E03, MSC 7510
Bethesda, MD  20892-7510
Rockville, MD  20852 (for express/courier service)

Applications must be received by July 11, 2000.  If an application is received 
after that date, it will be returned to the applicant without review.
  
The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application.  The 
CSR will not accept any application that is essentially the same as one 
already reviewed.  This does not preclude the submission of substantial 
revisions of applications already reviewed, but such applications must include 
an introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the NICHD.  Incomplete and/or non-responsive applications 
will be returned to the applicant without further consideration.

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 
the NICHD, in accordance with the review criteria stated below.  As part of 
the initial merit review, all applications will receive a written critique and 
may undergo a process in which only those applications deemed to have the 
highest scientific merit will be discussed, assigned a priority score, and 
receive a second-level review by the National Advisory Councils of the co-
sponsoring institutes..

Review Criteria

Specific Review Criteria for Adolescent Medicine Leadership Group (AMLG)

1.  Significance 

o  Adequacy of the proposed plans to address the intervention research agenda 
outlined in the Office of AIDS Research 1999 Status Report on NIH-sponsored 
Pediatric and Adolescent Research 
(http://www.nih.gov/od/oar/public/public.htm);

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

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

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

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

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

o  Adequacy of the plans for ATN policy development;

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

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

3.  Innovation

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

4.  Investigators

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

o  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;

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

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

1.  Significance

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

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

2.  Approach

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

o  Adequacy of the plans for supporting a managerial database in order to 
generate potential subjects available for proposed or  planned studies;

o  Flexibility of plans to respond to the changing analytic needs of the ATN.

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

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

3.  Innovation

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

4.  Investigators

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

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

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

Specific Review Criteria for Adolescent Medicine Trials Unit (AMTUs)

1.  Significance

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

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

2.  Approach

o  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;

o  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 populations) and plans to include both genders, minorities 
and their subgroups, and children as appropriate for the scientific goals of 
the research;

o  Strength and adequacy of the site’s management and communication plan;

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

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

3.  Innovation

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

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

4.  Investigators

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

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

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

5. Environment

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

o  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;

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

In addition to the above criteria, in accordance with NIH policy, all 
applications also will be reviewed with respect to the following:

o  The adequacy of plans to include both genders, minorities and their 
subgroups, and children as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects also will be 
evaluated.

o  The reasonableness of the proposed budget and duration in relation to the 
proposed research.

o  The adequacy of the proposed protection for humans, animals or the 
environment, to the extent they may be adversely affected by the project  
proposed in the application.

The initial review group also will examine the provisions for the protection 
of human subjects and the safety of the research environment.

SCHEDULE

Pre-application Meeting: March 25, 2000
  Marriott Crystal Gateway Hotel
  1700 Jefferson Davis Highway
  Arlington VA 22202
  9-10 a.m., Salon G  
Letter of Intent Receipt Date:    April 15, 2000 
Application Receipt Date:         July 11, 2000
Peer Review Date:                 October 2000
Council Review:                   January 25-26, 2001
Earliest Anticipated Start Date:  January 27, 2001

AWARD CRITERIA

Criteria that will be used to make award decisions include scientific and 
technical merit, as determined by peer review; availability of funds; and 
programmatic priorities.

INQUIRIES

Inquiries concerning this RFA are encouraged.  The opportunity to clarify any 
issues or questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues 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
Telephone:  (301) 435-6873
FAX:  (301) 496-8678
E-mail:  ar44n@nih.gov

Anne Willoughby, M.D., M.P.H. (Administrative issues)
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
Telephone:  (301) 402-0699
FAX:  (301) 496-8678
E-mail: aw55g@nih.gov 

Direct inquiries regarding fiscal matters to:

Ms. Mary Daley
Grants Management Branch 
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-1305
FAX:  (301) 402-0915
Email:  md74u@nih.gov
   
AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.865.  Awards are made under authorization of Sections 301 and 405 of the 
Public Health Service Act, as amended (42 USC 241 and 284) and administered 
under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 
74 and 92.  This program is not subject to the intergovernmental review 
requirements of Executive Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant and contract recipients to provide a 
smoke-free workplace and promote the non-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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