Full Text HD-96-009
 
ADOLESCENT MEDICINE HIV/AIDS RESEARCH NETWORK
 
NIH GUIDE, Volume 25, Number 31, September 20, 1996
 
RFA:  HD-96-009
 
P.T.


Keywords: 

 
National Institute of Child Health and Human Development
National Institute of Allergy and Infectious Diseases
National Institute on Drug Abuse
 
Letter of Intent Receipt Date:  October 15, 1996
Application Receipt Date:  November 19, 1996
 
PURPOSE
 
The National Institute of Child Health and Human Development (NICHD),
the National Institute of Allergy and Infectious Diseases (NIAID),
and the National Institute on Drug Abuse (NIDA) invite applications
for cooperative agreements to expand the clinical science component
of an existing adolescent health research network, the Adolescent
Medicine HIV/AIDS Research Network. This Network is conducting basic
and clinical research on the medical, biobehavioral, and psychosocial
aspects of HIV/AIDS in adolescents infected with HIV through sexual
or drug-taking behaviors.  The network, established in 1994, is
recruiting adolescents ages 12 through 18 years. Additional funding
from Health Resources and Services Administration (HRSA) has been
provided to the Network to fund the infrastructure to support
research in clinical sites including outreach efforts and to develop
and disseminate treatment and policy guidelines specific to
HIV-infected adolescents.
 
HEALTHY PEOPLE 2000
 
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), Adolescent Medicine HIV/AIDS Research
Network, centers on a high priority research area:  the health and
well-being of several special population groups, viz. people in
minority groups (particularly Hispanic and African Americans) and
people with low income, as well as specific research HIV infection
Needs.  Potential applicants may obtain a copy of "Healthy People
2000" (Full Report:  Stock No. 017-001-00474-0 or Summary Report:
Stock No. 017-001-00473-1) through the Superintendent of Documents,
Government Printing Office, Washington, DC 20402-9325 (Telephone
202-512-1800).
 
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.  Racial/ethnic minority
investigators, women, and persons with disabilities are encouraged to
apply.  It is required that applicants for the Clinical Science Group
have clinical experience pertinent to the objectives of the network
delineated in this RFA. Applications from individuals without this
experience will be returned without review. Applicants to join the
existing Clinical Science Group of this Network must be providing
comprehensive health care and support services to HIV-infected
adolescents. Furthermore, they must demonstrate the proven capacity
to reach sufficient numbers of adolescents with HIV infection to
satisfy subject accrual expectations. In addition, applicants must be
willing and able to participate in a cooperative program of research
and evaluation with other successful applicants and current Clinical
Science Group members.
 
MECHANISM OF SUPPORT
 
The administrative and funding instrument to be used for this program
will be a cooperative agreement (U01), 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.  [GRANTS POLICY
STATEMENT, DHHS PUBLICATION (OASH) 90-50,000 (REV) APRIL 1, 1994].
Under the cooperative agreement mechanism, 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.  Specifically, members of the NICHD,
NIAID, NIDA, and HRSA scientific and program staff will cooperate
with principal investigators as partners in the projects and serve as
science collaborators or program managers.  All parties will agree to
accept the participatory and cooperative nature of the group process.
Details of the responsibilities, relationship, and governance of the
study to be funded under cooperative agreements are discussed later
in this document under the section "Terms and Conditions of Award."
 
The total project period for applications submitted in response to
the present RFA may not exceed three years. The anticipated award
date is February, 1997. At this time, NICHD, NIAID, NIDA, and HRSA
have not determined whether or how this solicitation will be
continued beyond the present RFA.
 
Awards and level of support depend on receipt of a sufficient number
of applications of high merit.  Although this program is provided for
in the financial plans of NICHD, NIAID, NIDA, and HRSA, awards
pursuant to this RFA are contingent upon the availability of funds
for this purpose.
 
FUNDS AVAILABLE
 
It is estimated that $ 1,044,000 (total costs in fiscal year 1997)
will be available to fund approximately three to six awards to
support the scientific and subject accrual activity of the members of
the Clinical Science Group who are recruited through this RFA. Future
year funding will be determined based on initial funding level.  The
National Institute of Child Health and Human Development will provide
the total of these funds.
 
RESEARCH OBJECTIVES
 
Background of the Problem
 
Through December 1995, 2,354 AIDS cases in adolescents (aged 13-19
years) were reported to the National Centers for Disease Control and
Prevention.  Although adolescents comprise less than one percent of
all reported AIDS cases, the impact of HIV infection acquired during
adolescence is far more profound for several reasons.  First, the
long incubation period between initial HIV infection and the
development of AIDS-defining conditions suggests that the majority of
AIDS cases in persons between 20 and 29 years of age, which
constitute nearly 20 percent of all reported AIDS cases, can be
attributed to infection as teenagers.  Secondly, HIV infection, and
to some extent AIDS cases under the new case definition, are not
accurately estimated through reporting mechanisms because adolescents
lack easy access to medical care for diagnosis.  Many may actually
succumb to competing causes of mortality (e.g., violence).  Recent
blinded HIV serosurveys indicate a range of estimates: from
prevalence rates of 0.34 per 1000 in 17-19 year-old applicants to the
military, 1.7 per 1000 in the users of student health services on
selected college campuses, 3.9 per 1000 in Job Corps applicants, to
88 per 1000 in an urban homeless youth center.
 
Of the groups affected by HIV, the U.S. adolescent population is the
one in which basic biologic issues are the most poorly understood and
the one in which therapeutic and clinical management trials have not
been effectively initiated.  At the present time, it is not known how
HIV infection affects continuing development in those adolescents who
have been infected through sexual or injecting drug use practices.
It is not clear how age at infection influences the course of
maturation nor is it clear how maturation might proceed in HIV+
adolescents with repeated HIV sexual exposure, drug abuse, sexually
transmitted disease co-morbidity, and/or pregnancy.
 
The heterosexual transmission of HIV is attaining increasing
importance as a mode of HIV spread to uninfected individuals.  This
mode of HIV transmission is particularly important in the adolescent
population due to the high prevalence of high-risk behaviors.  The
factors which modulate the heterosexual transmission of HIV have not
been determined. However, it is likely that the replication of HIV at
genital mucosal surfaces plays a major role in the likelihood of the
occurrence of viral transmission following heterosexual exposure.
 
Background of the Adolescent Medicine HIV/AIDS Research Network and
the Scope of Its Research Agenda
 
This Adolescent Medicine HIV/AIDS Research Network initiative calls
for a descriptive examination of the full spectrum of HIV disease and
its behavioral manifestations in adolescents who have become infected
with HIV through sex and drug-taking behaviors in order to identify
and pursue an HIV/AIDS-specific research agenda in the adolescent
population between the ages of 12 and 19 years of age.  The ultimate
goal of this project is to achieve a better understanding of HIV
disease progression and co-morbidity in adolescents and thus improve
health care management. This goal is being addressed through the
enrollment of HIV-infected adolescents into a standardized base
protocol to characterize a population-based spectrum of disease,
disease progression, and the effect of comorbidity with drug abuse,
other sexually-transmitted diseases and pregnancy in the adolescent
population.  A secondary goal involves the resolution of remaining
questions related to HIV infection in adolescents through the
development of special studies to be undertaken in the assembled
cohort enrolled in the base protocol.  These unresolved questions
include but are not limited to the susceptibility, infectivity, and
transmissibility of HIV in adolescents, particularly related to
developing genital mucosa; the characterization of the variation in
adolescent immune function; the identification of useful
adolescent-specific clinical markers of HIV disease progression; the
effect of HIV on adolescent neuropsychologic function and
development; and the influence and effect of specific adolescent
behavioral patterns on risk-taking and health-seeking activities.
 
Organizational Components
 
The NIH entered into cooperative agreements establishing the network
in 1994. The Adolescent Medicine HIV/AIDS Research Network consists
of two interactive groups, Basic Science and Clinical Science,
managed by Steering and Executive Committees, supported by a Data and
Operations Center, advised by a Community Advisory Board, and
reviewed by a Scientific Advisory Panel. The current Network includes
an eight member Basic Science Group, a twelve member Clinical Science
Group, and a Data and Operations Center. The Basic Science Group, in
collaboration with the Clinical Science Group and a Data and
Operations Center, has produced a base protocol which addresses the
primary objective of the initiative.  The study began accruing
research subjects in February 1996.
 
This solicitation seeks cooperative agreements with investigators to
augment the subject accrual capacity of the Clinical Science Group in
order to establish a subject cohort of sufficient size to address
more completely the research objectives outlined above and thus
permit the conduct of a wide- ranging, multi-stage series of
investigations which examine specific facets of HIV infection in
adolescents.  This RFA is intended to recruit additional members of
the Clinical Science Group with responsibility for the (1)
implementation of the base protocol and secondary protocols where
feasible and the recruitment and monitoring of study participants,
associated data collection, and quality control; (2) participation in
the production of the supplemental research agenda through review and
evaluation at regularly scheduled interactive Network meetings; (3)
clinical management guidelines for the standardization of health care
delivery across network sites which address the unique biological,
biobehavioral, and psychosocial issues of adolescence including
pharmacologic prophylaxis, the scope and frequency of medical
monitoring, and service organization, overcoming barriers to care,
among others; and (4) the convening of consensus panels on the
dissemination of clinical management guidelines and the definition of
adolescent- specific HIV policy among other tasks consistent with
functioning as a national resource body.
 
SPECIAL REQUIREMENTS
 
Applications to become members of the Clinical Science Group must
submit evidence of clinical experience, comprehensiveness of health
care and support services, and availability of subjects. All members
of the Clinical Science Group are expected to participate in
conference calls and attend two Network meetings per year
contributing to the research and policy life of the Network.
 
Applicants must implement an existing base protocol which measures
health status, service utilization, sexual and drug-taking behaviors,
and psychological state at three month intervals over the duration of
the project. Sensitive information is collected through an
interactive computer interview and the data collected in this manner
are not available to the site personnel. Health status measures
include routine physical examinations and twice-yearly genital
examinations including PAP smears, cervicophotography,
cervico-vaginal lavage, and swabs. Anal swabs, radiologic examination
of the wrist to assess bone age, and drug assays are performed on all
subjects. HIV-positive youth will be assessed for disease progression
through virologic and immunologic measures, entailing blood draws,
urine collection, and delayed-type hypersensitivity assessment. No
measure will entail risk greater than that encountered within routine
history and physical examination for sexually active youth. There
will be no therapeutic intervention in this protocol, although
medical management (primary therapy, prophylaxis, and immunization
schedule) will be measured and its influence on outcome evaluated
within statistical constraints secondary to sample size. Applicants
should have access to AIDS Clinical Trials Group certified immunology
and/or virology laboratories.
 
Applicants should appropriately complete the human subjects sections
of the PHS 398; however, human subjects review by institutional
review boards (IRB) should be deferred until applications have been
evaluated by the NIH scientific review group. All applicants meeting
review criteria and recommended for funding will be provided a copy
of the base protocol and supporting documents for submission for
human subjects review while award criteria are evaluated. Successful
applicants will be required to have approved assurance and IRB
certification on file with the Office for Protection from Research
Risks, National Institutes of Health, and acquire a Certificate of
Confidentiality prior to the award of funds.
 
Terms and Conditions of Award
 
The following terms of award 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,
PHS, and NIH grant administration policies. Business management
aspects of these awards will be administered by the NICHD Grants
Management Office in accordance with HHS, PHS, and NIH Grant
Administration policies.  All awarded funds will be administered by
the NICHD Grants Management Office.
 
The administrative and funding instrument to be used for this program
will be a cooperative agreement (U01), an "assistance" mechanism
(rather than an "acquisition" mechanism) in which substantial NIH and
HRSA 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 resides 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 NICHD,
NIAID, NIDA, and HRSA staff collaborators. The research effort will
be a cooperative venture with participation by all awardees as
outlined below, the NICHD, the NIAID, NIDA, and HRSA.
 
The Primary Rights and Responsibilities of the Awardees
 
Basic Science Group:
 
The Basic Science Group consists of those awardees whose submissions
were chosen on the basis of scientific merit, representative(s) of
the Data and Operations Center (DOC), and the NICHD, NIAID, NIDA
staff collaborators. The Basic Science Group has a chair and vice
chair elected by its members for a two year term; NIH and HRSA staff
collaborators may not serve as officers. The Basic Science Group does
 
Retain the primary responsibility for defining and prioritizing the
research agenda and submitting the agenda to the Steering Committee
for approval;
 
Specify research objectives for the base study to characterize a
population-based spectrum of disease and disease progression and
secondary special studies, develop corresponding protocols, provide
for monitoring the progress of various studies, and analyze and
interpret study protocol results. It is expected that this
responsibility will be undertaken with significant interaction with
the members of the Clinical Science Group;
 
Consult and review Clinical Science Group plans for the evaluation of
clinical management guidelines which address the unique biological,
biobehavioral and psychosocial issues of adolescence including
pharmacologic prophylaxis, the scope and frequency of medical
monitoring, and organization of services, among others;
 
The full database for the base protocol will come from all funded
clinical sites; the full database for nested substudies may come from
all or a subset of the clinical sites. These databases will be
physically located at the Data and Operations Center and the use and
publication of these data will be governed by policies established by
the Executive Committee. NICHD, NIAID, NIDA, and HRSA staff
collaborators, in collaboration with the Executive Committee, may
have access to data generated under this cooperative agreement and
may use these data to generate internal reports of the Network
activities. Basic Science Group awardees, as a group, will retain
custody of and have primary rights to the protocol data developed
under these awards, subject to government rights of access consistent
with current HHS, PHS, and NIH policies. Protocol development for
special studies shall be undertaken when two-thirds of the Basic
Science Group members approve the research concept;
 
Performance Reports: Basic Science Group members must submit a
progress report as part of the annual application for noncompetitive
renewal.
 
Clinical Science Group:
 
The Clinical Science Group will consist of awardees, and the NICHD
and HRSA staff collaborators. The Clinical Science Group has a chair
and vice chair elected by its members for a two year term; NIH and
HRSA staff collaborators may not serve as officers. The Clinical
Science Group does
 
Participate in the production of the research agenda through review
and evaluation at regularly scheduled interactive Network meetings;
and by submitting concepts for study (both primary or secondary
analyses).  Clinical Science Group members will be strongly
encouraged to submit research concepts to the Basic Science Group and
may participate in their subsequent protocol development. Decisions
related to protocol development and protocol team formation are the
responsibility of the Basic Science Group;
 
Retain primary responsibility for the implementation of the base
protocol and secondary protocols where feasible and the recruitment
and monitoring of study participants, associated data collection, and
quality control;
 
Awardees will be required to accept and implement the common protocol
developed by the Basic Science Group and all procedures approved by
the Steering Committee;
 
Derive clinical management guidelines for the standardization of
health care delivery across network sites which address the unique
biological, biobehavioral, and psychosocial issues of adolescence
including pharmacologic prophylaxis, the scope and frequency of
medical monitoring, and service organization, overcoming barriers to
care, among others; and submit a corresponding evaluation plan to the
Basic Science Group for consultation and review;
 
The full database for the base protocol will be developed from
research data collected in all funded clinical sites; the full
database for nested substudies may come from all or a subset of the
clinical sites. These databases will be physically located at the
Data and Operations Center and the use and publication of these data
will be governed by policies established by the Executive Committee.
Data from individual sites may have limited value or may have
substantial independent scientific value for specific research
questions. The Executive Committee may establish policies encouraging
or limiting publication of such site- specific institutional data as
appropriate for a given circumstance. NICHD, NIAID, NIDA, and HRSA
staff collaborators, in collaboration with the Executive Committee,
may have access to data generated under this cooperative agreement;
and may use these data to generate internal reports of the Network
activities. Clinical Science awardees, as a group, will retain
custody of and have primary rights to the data specific to guidelines
evaluation developed under these awards, subject to government rights
of access consistent with current HHS, PHS, and NIH policies. Study
development for the secondary analyses of data generated through the
clinical management guideline evaluation shall be undertaken when
two-thirds of the Clinical Science Group members approve the research
concept;
 
Clinical Science awardees, as a group, will convene consensus panels
on the dissemination of clinical management guidelines and the
definition of adolescent- specific HIV policy among other tasks
consistent with functioning as a national resource body;
 
Clinical Science Group members will recruit two adolescent/family
member community representatives from each clinical site (one as
primary representative, and the other as an alternate), at least one
of whom from each site must be an adolescent between 15 and 19 years,
to serve on the Community Advisory Board;
 
Satisfy the expectations of participation in the Network committee
and group activities, research subject recruitment and retention,
timely data reporting and quality control measures. Individual awards
may be curtailed or terminated by the government if these
expectations are not met, or a major breach of protocol, or
substantive protocol changes are undertaken without prior approval
from the staff collaborators and Basic Science Group members;
 
Performance Reports: Clinical Science Group members must submit as
part of the progress report for the non-competing continuation
application information detailing progress towards achieving patient
accrual and retention goals and other measures of performance
(including followup activities, data quality, timeliness of data
submission, proportion of required repository specimen volumes
collected and sent to Central Repository, and specific contributions
to the Network's agenda which involves active participation in the
scientific and clinical research activities of the Network). The
purpose of this report is to inform funding requirements for the
remaining budget period. Future year funding is contingent upon
persistent satisfactory performance in meeting goals and measures
noted above;
 
Existing Track B awardees will be required to comply with the
reporting requirements imposed on HRSA funded Title IV
Pediatric-Adolescent Demonstration Projects.
 
The Data and Operations Center (DOC):
 
The Data and Operations Center does
 
Manage all meetings of the Network, Basic and Clinical Science Groups
as well as the Community and Scientific Advisory Boards including
necessary conference calls among members;
 
Support protocol development and distribution; and assume
responsibility for protocol site registration and training,
site-monitoring for subject safety, data collection practices, and
regulatory compliance;
 
Support development of clinical management guidelines assuming
responsibility for required consensus conferences and guidelines
dissemination;
 
Remain responsible for the integrity of the scientific databases and
provide statistical consultation during protocol development as well
as timely analyses;
 
Program Staff Involvement:
 
The research effort is a cooperative venture with participation by
all awardees as outlined above, the NICHD, the NIAID, the NIDA, and
HRSA. One NICHD, one NIAID, one NIDA, and one HRSA staff collaborator
do:
 
Participate in the Steering Committee which oversees the
establishment and maintenance of the Network and Network progress in
achieving program goals;
 
Assist the Basic Science Group in the selection of research topics
and the development of protocols for specific studies and
interventions;
 
Assist the Clinical Science Group in the development and evaluation
of the clinical management guidelines;
 
Arrange, when necessary, for the external peer review of the
protocols for the base study, special studies, and clinical
management guideline evaluation clearing these studies for
implementation;
 
Explore mechanisms to offer study subjects the opportunity to
participate in clinical drug trials funded through mechanisms outside
the network and provide this information and organizational support
to clinical sites;
 
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 in data analyses, interpretation and publication of study
results.
 
Collaborative Responsibilities:
 
The Research Network
 
The Research Network is composed of all principal investigators of
the Basic Science Group, all principal investigators of the Clinical
Science Group, all members of the Study Coordinators Group, all
representatives of the Community Advisory Board, the principal
investigator and project coordinator from the Data and Operations
Center, the NICHD, the NIAID, NIDA, and HRSA. The entire Network will
attend interactive annual meetings to inform and review the research
agenda.
 
The Steering Committee
 
The Steering Committee is the main governing body of the Network.
The Committee is composed of the Chair, Vice Chair, and two elected
representatives from the Basic Science Group; the Chair, Vice Chair,
and two elected representatives from the Clinical Science Group; the
Chair and Vice Chair of the Study Coordinators Group; the Chair and
Vice Chair of the Community Advisory Board; the principal
investigator and project coordinator from the Data and Operations
Center; and the NICHD, the NIAID, the NIDA, and the HRSA staff
collaborators. All members will have one vote each; NICHD, NIAID,
NIDA, and HRSA will have one vote each, and motions will carry with
simple majority. The Chair and Vice Chair of the Steering Committee
will be elected by the entire committee from among the principal
investigators of the Basic Science Group and the Clinical Science
Group; none of the NICHD, NIAID, NIDA, or HRSA staff collaborators
are eligible to serve as Chair or Vice Chair of the Steering
Committee.
 
The Steering Committee will
 
Maintain primary responsibility for 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 research agenda specific to its feasibility and clinical
relevance and advise on the development of implementation strategies;
 
Approve the clinical management guidelines addressing the unique
biological, biobehavioral, and psychosocial issues of adolescence
including pharmacologic prophylaxis, the scope and frequency of
medical monitoring, and service organization, among others; and the
plans for their evaluation.
 
The Executive Committee
 
The Steering Committee chairperson will chair the Executive Committee
as well. The Executive Committee, composed of the Steering Committee
chair and vice chair, the chair and vice-chair of the Basic Science
Group, the chair and vice chair of the Clinical Science Group, the
principal investigator and project coordinator of the Data and
Operations Center, the NICHD, NIAID, NIDA, and HRSA staff
collaborators, will supervise the functioning of the network and will
 
Establish timelines for the completion of tasks and monitor progress;
 
Coordinate the integration of data collection for base protocol and
guidelines evaluation procedures;
 
Oversee site participation and performance informing the appropriate
program managers;
 
Define rules regarding access to data and publication and direct the
publication process.
 
Study Coordinators Group
 
The Study Coordinators Group is composed of all the primary research
nurses or associates at the clinical sites supported by the grant
award. The Study Coordinators Group, with a chair and a vice chair
elected for a two year term, does
 
Recommend issues of concern to be studied within the research agenda
and collaborate on their development;
 
Advise on the Network's subject recruitment and retention strategies;
 
Review and evaluate the study and evaluation research protocols for
acceptability and feasibility;
 
Review and evaluate subject protection procedures and confidentiality
of records in support of the Clinical Science Group principal
investigators;
 
Review and evaluate the integrity of data collection procedures in
support of the Clinical Science Group principal investigators;
 
Provide consultation to the Clinical Science Group at consensus
conferences for policy or management affecting HIV+ youth.
 
Community Advisory Board
 
The Community Advisory Board will consist of two adolescent or family
member community representatives from each clinical site, one of whom
must be an adolescent between 15 and 19 years of age and who are to
be chosen by the principal investigator at the corresponding clinical
site. The Community Advisory Board will
 
Recommend issues of concern to be studied within the research agenda;
 
Choose a chair and vice-chair to coordinate and organize its
Community Advisory Board meetings and conference calls and represent
community interests on the Steering Committee;
 
Advise the Network on subject recruitment and retention strategies;
 
Review and evaluate the study and evaluation research protocols for
acceptability and feasibility;
 
Provide consultation to the Clinical Science Group at consensus
conferences for policy or management affecting HIV+ youth.
 
Scientific Advisory Panel
 
A Scientific Advisory Panel, consisting of federal and non-federal
experts in the disciplines related to the Network's research agenda,
will be appointed by the NICHD in consultation with NIAID, NIDA, and
HRSA and will report directly to the Director, NICHD. The Scientific
Advisory Panel will undertake the following functions:
 
Review and evaluate the overall direction, objectives, content and
progress of the Basic Scientific Research Agenda in an annual meeting
or more frequently if necessary;
 
Review and evaluate the overall direction, objectives, content and
progress of the Clinical Management Evaluation Research Agenda in an
annual meeting or more frequently if necessary.
 
Data and Safety Monitoring Board
 
The intention of the Network is to establish a cohort of adolescents
for whom an observational study will be conducted. No primary
intervention studies were envisioned in the original RFA.  However,
the potential for the implementation of intervention studies exists,
particularly in the area of secondary prevention strategies and the
evaluation of clinical management guidelines.  If this potential is
realized, the NICHD, NIAID, NIDA, and HRSA science collaborators will
establish a Data and Safety Monitoring Board and establish procedures
for its conduct.  Any Data and Safety Monitoring Board will report to
the NIH and HRSA science collaborators and the Network Steering
Committee.
 
Approval Process for Research Undertaken in the Network
 
The Basic Scientific Agenda will be approved in the following manner:
 
Potential research areas will be proposed through multiple
mechanisms, including professional (internal and external to Network)
and community presentations/ sessions at the Research Network
meetings, as well as individual concept proposals submitted by
principal investigators (alone or in collaboration);
 
The Basic Science Group, supported by the Data and Operations Center,
will define and prioritize the agenda, assess the merit of concept
sheets, proposing protocol development around those with specific
study hypotheses consistent with the research agenda, returning
others to proposing investigators with constructive comments
attached;
 
The Clinical Science Group will review and evaluate the agenda and
proposed protocol(s);
 
The Community Advisory Board will review and evaluate the agenda and
proposed protocol(s);
 
The Steering Committee will vote to approve the Network Scientific
Agenda; if approved the protocol will be forwarded to the Scientific
Advisory Panel; if unapproved, the protocol will be returned to the
Basic Science Group;
 
Before implementation of the base protocol in the first year, the
Scientific Advisory Panel will review its direction, its objectives,
and its content; the Scientific Advisory Panel will meet annually (or
more frequently if necessary) thereafter to review the direction and
progress of the Network Scientific Research Agenda.
 
The Clinical Management Evaluation Research Agenda will be approved
in the following manner:
 
The development of the Clinical Management Guidelines is the
responsibility of the Clinical Science Group, alone or in
consultation with clinical expertise and community experience
external to the Network, and supported by the Data and Operations
Center;
 
The Clinical Science Group will define the scope of the guidelines
and propose hypothesis-driven evaluation for their effectiveness;
 
The Basic Science Group will review the research protocol for the
clinical management guidelines evaluation;
 
The Community Advisory Board will review the evaluation research
protocol;
 
The Steering Committee will vote to approve the evaluation research
protocol; if approved the protocol will be forwarded to the
Scientific Advisory Panel; if unapproved, the protocol will be
returned to the Clinical Science Group;
 
Before implementation of the evaluation protocol in the first year,
the Scientific Advisory Panel will review its direction, its
objectives, and its content; the Scientific Advisory Panel will meet
annually (or more frequently if necessary) thereafter to review the
direction and progress of the Clinical Management Evaluation Research
Agenda.
 
Arbitration Process
 
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,
NIAID, NIDA, and HRSA science collaborators not voting) or by the
individual awardee in the event of an individual disagreement, a
second member selected by the science collaborators, 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 new policy
results from the NIH Revitalization Act of 1993 (Section 492B of
Public Law 103-43) and supersedes and strengthens the previous
policies (Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations), which
have been in effect since 1990. The new policy contains some
provisions that are substantially different from the 1990 policies.
 
All investigators proposing research involving human subjects should
read the "NIH Guidelines for Inclusion of Women and Minorities as
Subjects in Clinical Research," which have been published in the
Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted
in the NIH Guide for Grants and Contracts, Volume 23, Number 11,
March 18, 1994.
 
Investigators also may obtain copies of the policy 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, by October 15, 1996, a
letter of intent that includes a descriptive title of the proposed
research, the name, address and telephone number of the Principal
Investigator and the number and title of the RFA in response to which
the application may be submitted.
 
Although a letter of intent is not required, is not binding, and does
not enter into the review of subsequent applications, the information
that it contains is helpful in planning for the review of
applications.  It allows NICHD staff to estimate potential review
workload and to avoid conflict of interest in the review.
 
The letter of intent is to be sent to:
 
Audrey Smith Rogers, Ph.D., M.P.H.
Center for Research for Mothers and Children
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 4B11, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-7339
 
APPLICATION PROCEDURES
 
Applications are to be submitted on PHS Form 398 (rev. 5/95).
Applications kits are available at most institutional offices of
sponsored research and may be obtained from the Grants Information
Office, Office of Extramural Outreach and Information Resources,
National Institutes of Health, 6701 Rockledge Drive, MSC 7910,
Bethesda, MD 20892-7910, telephone 301/435-0714, email:
ASKNIH@odrockm1.od.nih.gov; and from the NIH program administrator
named below.
 
Materials to Include in the Application
 
To permit evaluation of the merits of an application (peer review),
information is needed on the following topics.
 
Applications to become members of the Clinical Science Group must
include
 
1. Documentation of three or more years of clinical experience in
adolescent health care for the physician candidate for the Clinical
Science Group;
 
2. A description of the physical structure and administrative
arrangement for the site at which health care and support services
are provided (including hours of operation, provision for off-hour
coverage, and established patterns of referral);
 
3. Evidence of an interdisciplinary approach to the delivery of
adolescent health care and support services ( the breadth of services
and qualifications of the corresponding providers should be listed
and described);
 
4. Demonstration of availability of on-site gynecologic services and
case management, on-site or established and functioning referral
networks for mental health services, substance abuse treatment, and
enabling services such as childcare and transportation;
 
5. Numbers of the adolescent population categorized by ages 10-11,
12-14, 15- 17 years currently served by the clinic;
 
6. Description of the population in #5 must include gender,
race/ethnicity, and should include (if available) socioeconomic
strata, educational achievement, blinded serosurveys of HIV
infection, AIDS cases numbers (cumulative and annual), STD and
pregnancy rates, substance abuse statistics, and other evidence of
high risk behaviors. If women or minorities are excluded or
inadequately represented in clinical research, particularly in
proposed population-based studies, a clear and compelling rationale
must be provided;
 
7. Evidence of ability to enroll 20 HIV-infected adolescents and 10
HIV- negative but high risk adolescents between the ages of 12 and 19
years within the first year of funding;
 
8. The interaction between the clinic and the community it serves
should be described. Of specific interest are community advisory or
consultative groups which have substantial adolescent participation,
efforts at parental or community education, clinic policies for
adolescent involvement in their own care and details of existing or
planned community outreach and prevention programs to identify
adolescents and bring them into care;
 
9. Budgets for the Clinical Science Group applications should include
physician principal investigator salary support at 0.10 FTE, clinical
associate/research nurse at 1.0 FTE, and three research visits for
study subjects (estimated by comprehensive routine
physical/laboratory examination costs, HIV RNA PCR and culture, and
immunologic panel for subjects for three research encounters). Travel
for the principal investigator and the research nurse should be
requested to two (three day meetings) in the Washington DC area. A
budget worksheet is available on request and its use is strongly
recommended.
 
This application will be used to judge the clinical expertise and
technical proficiency of the applicant and should not exceed the 25
page limit (including graphics) for the entire submission.
 
For all applications, the RFA label available in the application form
PHS 398 must be affixed to the bottom of the face page.  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
evaluation.  In addition, the RFA title  ("Adolescent Medicine
HIV/AIDS Research Network") and number must be typed on line 2 of the
face page of the application form and the "YES" box must be marked.
 
The signed, typewritten original of the application, including the
Checklist, and three signed photocopies must be sent or delivered in
one package to:
 
DIVISION OF RESEARCH GRANTS
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, in addition to the applications and copies
mailed to the Division of Research Grants, two copies of the
application must be sent under separate cover to:
 
Susan Streufert, Ph.D., Director
Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5E01 - MSC 7510
Bethesda, MD  20892
Bethesda, MD  20852 (for express/courier service)
 
Applications must be received by close of business on November 19,
1996.  If an application is received after that date, it will be
returned to the applicant without review.  The Division of Research
Grants (DRG) 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 DRG will
not accept any application that is essentially the same as one
already reviewed.  This does not preclude the submission of a
substantial revision of an application already reviewed, but such an
application must follow the guidance in the PHS 398 application
instructions for the preparation of revised applications, including
an introduction addressing the previous critique.
 
REVIEW CONSIDERATIONS
 
Upon receipt, applications will be reviewed for completeness by DRG
and responsiveness by the NICHD.  Incomplete applications will be
returned to the applicant without further consideration.  If the
application is not responsive to the RFA, the application will be
returned to the applicant.  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, a process may be used by the
initial review group in which applications will be determined to be
competitive or non-competitive based on their scientific merit
relative to other applications received in response to the RFA.
Applications judged to be competitive will be evaluated for
scientific and technical merit and assigned a priority score.
Applications determined to be non-competitive will be withdrawn from
further consideration and the Principal Investigator and the official
signing for the applicant organization will be notified and receive a
summary statement containing reviewers' comments.
 
Review Criteria:
 
Clinical training and experience of project staff specific to
adolescent care;
 
Evidence of an interdisciplinary approach;
 
Adequacy of site characteristics as described in this RFA;
 
Appropriateness of the plans for inclusion of women and minorities;
 
Appropriateness of recruitment and retention methods and willingness
to work as part of the cooperative study with existing awardees and
NICHD, NIAID, NIDA, and HRSA scientists.
 
The review group will also examine the provisions for the protection
of human and animal subjects, the safety of the research environment,
and the appropriateness of accompanying budget.
 
AWARD CRITERIA
 
Applications recommended by the National Advisory Council to the
National Institute of Child Health and Human Development will be
considered for award based upon (a) merit as reflected in the
priority score; (b) program balance including sufficient
compatibility of features to make a successful collaborative program
likely; (c) availability of funds; (d) identified needs in the
established network.
 
Schedule
 
Letter of Intent Receipt Date:     October 15, 1996
Application Receipt Date:          November 19, 1996
Review by NICHD Advisory Council:  January 1997
Anticipated Award Date:            February 1, 1997
 
INQUIRIES
 
Inquiries 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., M.P.H.
Center for Research for Mothers and Children
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 4B11 - MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-7339
FAX:  (301) 496-8678
Email:  rogersa@hd01.nichd.nih.gov
 
Judy Lew, M.D.
Division of AIDS
National Institute of Allergy and Infectious Diseases
6003 Executive Boulevard, MSC 7620
Bethesda, MD  20892-7620
Telephone:  (301) 496-6178
Email:  jlew@exec.niaid.pc.niaid.nih.gov
 
Katherine Davenny, M.P.H.  or Vincent Smeriglio, Ph.D.
Division of Clinical and Services Research
National Institute of Drug Abuse
5600 Fishers Lane, Room 11A33
Rockville, MD  20857
Telephone:  (301) 443-1801
Email:  kdavenny@aoada.ssw.dhhs.gov
Email:  vsmerigl@aoada.ssw.dhhs.gov
 
Direct inquiries regarding administrative/fiscal matters to:
 
Ms. Mary Daley Tozzolo
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17F - MSC 7510
Bethesda, MD  20852-7510
Telephone:  (301) 496-1303
Email:  tozzolom@hd01.nichd.nih.gov
 
AUTHORITY AND REGULATIONS
 
This program is described in the Catalog of Federal Domestic
Assistance No. 93.865.  Awards are made under the authorization of
the Public Health Service Act, Title IV, Part A (Public Law 78-410,
as amended by Public Law 99-158, 42 USC 241 and 285)  and
administered under PHS grants policies and Federal Regulations 42 CFR
52 and 45 CFR Part 74.  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.
 
.

Return to RFAs Index

Return to NIH Guide Main Index


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.