NATIONAL DRUG ABUSE TREATMENT CLINICAL TRIALS NETWORK

Release Date:  January 11, 1999

RFA:  DA-99-004

P.T.

National Institute on Drug Abuse

Letter of Intent Receipt Date:  March 13, 1999
Application Receipt Date:  April 13, 1999

PURPOSE

The National Institute on Drug Abuse (NIDA) invites cooperative agreement
applications from established clinical investigators to participate in the
National Drug Abuse Treatment Clinical Trials Network (CTN).  Awardees will
conduct and participate in coordinated multi-site clinical trials of behavioral,
pharmacological, and combined behavioral/pharmacological therapies for drug abuse
and addiction, and conduct research on practices, i.e., studies of factors that
impact upon successful adoption of new treatments.  CTN research is carried out
in community-based treatment settings, in collaboration with other awardees and
with NIDA.  Each awardee will function as a CTN Research Node, consisting of a
Regional Research and Training Center (RRTC) that is linked in partnership with
community-based treatment programs (CTPs). The CTN will consist of multiple
Nodes, and each Node will work in concert with other Nodes and NIDA to conduct
multisite and cross-regional (nationwide) clinical trials research.  Awardees
will deliver and test an array of both behavioral and pharmacological treatments
and determine conditions under which novel treatments are successfully adopted. 
Most studies to be conducted will span multiple sites, populations and geographic
regions. As a cooperative agreement, there will be substantial NIDA involvement
in the management and administration of the CTN, including in the determination
of which trials will be implemented using components of the Network.

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 RFA, National Drug Abuse Treatment
Clinical Trials Network, is related to the priority areas of "tobacco, alcohol
and other drugs, and HIV infection."  Potential applicants may obtain a copy of
"Healthy People 2000" (Full Report:  Stock No. 017-001-00474-0) or "Healthy
People 2000" (Summary Report:  Stock No. 017-001-00473-1) through the
Superintendent of Documents, Government Printing Office, Washington, D.C. 
20402-9325  (telephone 202-512-1800).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic for-profit and nonprofit organizations,
private and public, such as universities, colleges, hospitals, laboratories,
units of State or local governments, and eligible agencies of the Federal
Government.  Racial/ethnic minority individuals, women and persons with
disabilities are encouraged to apply as principal investigators.  Foreign
applicants are not eligible, and domestic applications may not include a foreign
site.  Because of the complexity of the proposed research and need for
collaboration, principal investigators should be able to document a substantial
history of managing complex research initiatives in clinical sites and have an
extensive publication record in clinical research.

MECHANISM OF SUPPORT

The administrative and funding instrument to be used for this program will be a
cooperative agreement (U10), an "assistance" mechanism (rather than an
"acquisition" mechanism), in which substantial NIH scientific and/or programmatic
involvement with the awardee is anticipated during 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
awardee recipient in a partner role, but it is not to assume direction, prime
responsibility, or a dominant role in the activity.  Details of the
responsibilities, relationships and governance of the study to be funded under
cooperative agreement(s) are discussed later in this document under the section
"Terms and Conditions of Award."

All policies and requirements that govern the grant program of the U.S. Public
Health Service (PHS) and the National Institutes of Health (NIH) apply.

FUNDS AVAILABLE

NIDA has set aside $10.0 million total costs for the first year of funding.  This
level of support is dependent on the receipt of a sufficient number and diversity
of applications of high scientific merit. NIDA expects to make up to four awards
this year under this RFA for project periods of up to five years of support.  It
is anticipated that there will be subsequent RFAs to expand the CTN and that
competing continuation applications will be invited upon expiration of the
initial funding period of awards made under the present RFA, subject to the
availability of funds.

Because the nature and scope of the research activities proposed in response to
this RFA may vary, it is anticipated that the size of individual awards will vary
also. Budget requests should be carefully justified and commensurate with the
complexity of the project. Although this program is provided for in the financial
plans of the NIDA, awards pursuant to this RFA are contingent upon the
availability of funds for this purpose.

RESEARCH OBJECTIVES

Background

Research has provided substantial evidence in support of the concept that drug
addiction is in many cases a chronic relapsing disease. As is the case for other
chronic disorders, effective treatments for addiction exist.  However, again as
is the case for other illnesses, the treatment of addiction can be improved;
considerable research has been directed towards that effort in the past.  The CTN
is designed to accelerate significantly the pace of treatment research and its
application to real-life treatment settings.

The improvement of existing treatments and development of new treatments based
upon findings in basic behavioral and neurobiological sciences are important
national research goals.  In recent years this research effort has yielded a
number of promising new behavioral treatment approaches.  However, the efficacy
of these new treatments has been demonstrated primarily in specialized treatment
research settings, with somewhat restricted patient populations. As a
consequence, few of these new treatments are being applied on a wide-scale basis
in real-life practice settings.  Research is needed to validate new science-based
treatments for drug abuse and addiction across a variety of community-based
treatment settings and with diverse patient populations and to implement or adapt
these treatments in community-based practice.

For medications, the situation is somewhat different.  Only three medications
have been approved by the Food and Drug Administration (FDA) for the treatment
of opiate addiction: methadone, LAAM, and naltrexone.  There are no approved
medications for the treatment of cocaine, methamphetamine, or marijuana  abuse
and addiction.  Thus, the range of options available for the use of medications
to treat drug addiction is quite limited.  However, NIDA-supported researchers
have now tested an array of both new and existing medications for specific
applications, and some are now ready for clinical trials in community settings.
The engagement and participation of community-based treatment providers in large-
scale clinical trials of potential therapeutic agents is essential for full and
appropriate testing and to ensure the acceptability and availability of agents
after FDA approval.

As in other fields of medicine, providers in the area of drug abuse and addiction
are often slow to adopt new treatments.  This can be due to such factors as
inadequate dissemination strategies, organizational or funding  constraints, or
resistance to change on the part of management or staff.  Transporting treatments
from research to practice is itself an important research area that has too often
been ignored in clinical research.

The National Drug Abuse Treatment Clinical Trials Network (CTN) is thus being
established to meet two major needs:  First, a research infrastructure is needed
to test the effectiveness and usefulness of new and improved treatments in real-
life settings with diverse patient populations.  Second, a mechanism is needed
for the systematic study of processes and factors involved in the incorporation
of new and improved interventions into community-based drug treatment. The
development of such a network has been recommended by the National Advisory
Council on Drug Abuse and is consistent with conclusions of Physicians Leadership
on National Drug Policy.  It also is the principal recommendation of the
Institute of Medicine/National Academy of Sciences report Bridging the Gap
Between Practice and Research: Forging Partnerships with Community-Based Drug and
Alcohol Treatment.  These organizations consider such a network to be essential
for improving the quality of treatment of drug abuse and addiction in this
country.  The CTN is expected to forge partnerships among NIDA, treatment
researchers and community-based treatment providers.  Establishment of strong
partnerships between researchers and practitioners is essential to assure that
new treatments address the critical needs of community-based treatment programs
and are suitable for those settings.  Through this joint effort, the gaps in
current treatment approaches will be addressed, yielding community-proven
treatments ready for adoption into clinical practice.

Objectives and Scope

The overall goal of the National Drug Abuse Treatment Clinical Trials Network is
to improve the quality of drug abuse treatment throughout the nation, thereby
reducing the prevalence, morbidity and mortality of drug abuse and addiction. 
Specific objectives include:

-  Supporting studies of behavioral, pharmacological, and combined behavioral and
pharmacological treatment interventions of established efficacy in rigorous, 
multi-site clinical trials to determine effectiveness across a broad range of
treatment settings and patient populations.

-  Encouraging research on the translation of science-based, effective treatment
interventions into clinical practice by establishing effectiveness in community-
based treatment programs and by determining effective strategies for transporting
effective treatments.

-  Furthering the development of effective treatments by integrating behavioral,
pharmacological, and practice research.

-  Investigating the impact of advances in treatment research on community-level
treatment practices.

-  Ensuring that treatment research in drug abuse and addiction meets the needs
of the wider community, including minorities, women, children, and underserved
populations.

-  Fostering the collaboration of community treatment practitioners and
researchers, to provide opportunities for bi-directional education and exchange
of ideas, information and values between the treatment and academic communities.

-  Determining the impact of the transport of novel, effective treatments to the
community on the incidence and prevalence of various other illnesses and
conditions, including such blood-borne infections as HIV and hepatitis.

Characteristics of the Network

The CTN will provide the nation a stable, broadly representative infrastructure
for drug abuse treatment research.  It is anticipated (pending availability of
funds for an expanded CTN) that regional Nodes, each consisting of an RRTC and
its affiliated CTPs, will be distributed throughout the country.  Each Node will
encompass a substantial geographical area and a variety of treatment settings,
patient populations, and drug abuse problems. RRTCs must have demonstrated
expertise in conducting drug abuse clinical trials and in research and clinical
training.  The community-based treatment programs will reflect the disparate
sites where treatment is now delivered.  For the CTN to be maximally effective,
the CTPs must be partners in the research enterprise, including participation in
decisions concerning selections of trials to be implemented and protocol design. 
Through its associated treatment programs, each Node must demonstrate the
capacity to recruit and treat a broad range of patients, including children,
women, patients with co-occurring mental disorders, those at high risk for HIV
infection, members of various racial/ethnic groups, and those abusing or addicted
to various drugs of abuse.  All Network Nodes must demonstrate the capacity to
deliver and test a variety of both pharmacological and behavioral treatments.

Examples of the types of studies appropriate for the CTN include:

-  Studies to determine if behavioral therapies, found to be efficacious in
smaller-scale studies, are effective in community clinics and for different
patient profiles.  The term "behavioral therapy" is used here in the broadest
sense, and is meant to include, for example, counseling, various aspects of
therapeutic community approaches, cognitive behavioral therapy, operant
behavioral therapy, and family therapy.

-  Studies to develop effective techniques for transporting new behavioral
therapies into community-based treatment programs.  For example, the
effectiveness of various approaches to therapist training could be compared
within the clinical-trial context.  In this fashion, information can be gained
not only about whether a therapy performs better than standard care, but also
about how a therapy may be transported.

-  Studies examining the impact of drug addiction treatment and AIDS risk
reduction counseling on HIV risk behaviors and/or seroconversion in both heroin
and cocaine addicts.  The Network could provide a sample representative of
diverse drug addicted populations sufficient to determine relative efficacy of
various approaches in different subgroups.

-  Studies pursuing the identification and development of pharmacologic
interventions for drug dependence treatment in multi-site settings.  The safety
and efficacy of the investigational pharmacologic agents will be tested in
accordance with FDA regulations, typically  by use of double blinded, placebo-
controlled or active-controlled designs. Such trials will also contain documented
plans of Good Clinical Practice (GCP) including assurance of regulatory
compliance with respect to submissions of protocols to the IRB and the FDA.

-  Studies aimed at optimizing the access to and effectiveness of currently
marketed pharmacotherapies for treatment of drug abuse and addiction.  Examples
are studies  to determine the optimal approach for integrating medications with
behavioral therapies at optimal levels and doses, such as naltrexone with
cognitive behavioral therapy, or LAAM with drug addiction counseling.

-  Behavioral intervention studies aimed at improving compliance with medication
regimens in patients with comorbid addictive and mental or physical disorders. 
For example, studies could be done to determine the best behavioral interventions
to ensure antiviral medication compliance in drug addicted individuals with AIDS,
or to investigate the effectiveness of a new behavioral intervention for patients
with bipolar disorder.

-  Studies of factors impacting transmission of knowledge, change in treatment
organizations, adaptation of new treatments and their adoption into widespread
clinical practice.

-  Research to develop models for integrating new behavioral interventions into
existing clinical practices, including levels of theoretical and practical
knowledge needed by practitioners, how to assess patient need for the new
intervention, how the new treatment is staged or incorporated into an ongoing
treatment regimen, how to measure program performance, outcomes, and cost-
benefits for the new intervention, and how to integrate the new treatment with
linked services.

-  Given that drug addiction and the spread of HIV/AIDS are intertwined
epidemics, the CTN will provide a vehicle to help facilitate reduction in risk
behaviors.  Toward that end, all CTPs will provide HIV risk reduction counseling
and offer HIV testing.  Research into the most effective approaches to outreach
and risk reduction counseling might also be incorporated into the activities of
some Nodes.

The CTN, with its core of community treatment programs engaging diverse
populations, is also designed to provide a much-needed vehicle to recruit and
study subjects for such related topics as the medical consequences of long-term
drug use and the genetics of vulnerability to addiction, to be funded under
separate research grants.  Although not all Nodes would be expected to have the
capacity to conduct such studies, all Nodes will be expected to relate
collaboratively to the research community focusing on such issues, and to aid in
recruitment of appropriate subjects.

Research will be conducted collaboratively involving NIDA, RRTCs, and CTPs.  The
structure of the network will permit rapid and concurrent multi-site testing of
a wide range of promising science-based therapies in statistically powerful
designs.  It is the intent of this national network that virtually all studies
will involve multiple Nodes working in concert.  The number of Nodes involved in
specific studies will vary depending on the nature of the scientific question
under study and the number and diversity of patients required.

Organization of the Network

The CTN will ultimately include a substantial number of regional Nodes, each
consisting of an RRTC and 5 to 10 or more  community treatment programs, linked
to the RRTC, representing diverse types of treatment facilities and patient
populations across a broad geographical area.  Each RRTC will develop protocols,
coordinate multisite clinical trials conducted within the community treatment
programs, provide and coordinate practitioner/therapist training, and collect,
analyze and maintain research data.  Each community treatment program will
recruit and treat patients participating in clinical trials, and participate in
the design of protocols in which they are involved.  A Network Steering
Committee, composed of principal investigators, community treatment program
representatives, and NIDA staff, will constitute the primary operating and
decision-making body of the CTN.

A.  Node.  A Node is defined as an RRTC with all of its associated Community
Treatment Programs.  The Node embodies a research partnership between the RRTC
and its CTPs.  The Clinical Trials Network will comprise multiple Nodes.  For
each research project undertaken within the CTN, one Node will be designated as
Lead Node by the Steering Committee.

B.  Regional Research and Training Center (RRTC).  The primary function of the
Regional Research and Training Center (RRTC) is to coordinate multi-site research
projects that will be carried out within Community Treatment Programs (CTPs). 
For every research project, each participating RRTC will have the responsibility
for coordination of research within its own Node.  For the Lead Node on each
project, the RRTC will have the additional responsibility of recruiting the
participation of other Nodes, coordinating research across multiple Nodes, and
providing comprehensive administrative and scientific management of the research
done across Nodes.  Data from all of the Community Treatment Programs for a given
study will be aggregated by the respective participating RRTCs and will be
forwarded to the Lead Node.

RRTC responsibilities include:

-  To contract with at least five CTPs in the first year, and at least ten in
subsequent years, to conduct the research of the CTN.  Under guidance of the
Network Steering Committee to ensure consistency across the Network, the RRTC
shall establish policies and procedures for assuring the quality of care of
participating CTPs and conducting periodic reviews of each CTP.  These reviews
shall examine patient accrual, data accuracy and timeliness, compliance with
study protocols, and audit results.

-  In partnership with its related CTPs, to develop and submit concepts/protocols
to the Steering Committee for approval and implementation.  Communication with
NIDA Scientific Collaborators and with other Nodes is required at all stages of
protocol conceptualization and development.

-  To implement trials as a Lead Node, coordinating studies with other Nodes
across the CTN, as well as to participate, with its CTPs, in studies coordinated
by other Lead Nodes.  In the latter case, other participating RRTCs will be
responsible for providing, under the direction of the Lead Node, data management,
quality control, training and supervision of CTP treatment providers, and for
transmitting data to the Lead Node.

-  To ensure adequate accrual of subjects from participating CTPs to meet the
requirements of each protocol in numbers recruited over defined time periods.

-  To establish and implement mechanisms for data management and analysis that
ensure data collection and management procedures are a) adequate for quality
control and analysis; b) as simple as is appropriate in order to encourage
maximal participation of CTPs entering patients and to avoid unnecessary expense;
c) in accordance with procedures and requirements established by the Steering
Committee; and d) sufficiently uniform across its CTPs and CTPs from other
participating Nodes.

-  To monitor adverse events and to report on all ongoing clinical trials to the
Data and Safety Monitoring Board in accord with policies and procedures to be
determined by the Board.

-  To establish a mechanism for interim monitoring of results and of protocol
progress, to be reported at least quarterly to the Network Steering Committee and
to NIDA.  If the Lead Node wishes to close accrual to a study prior to meeting
the established accrual goal, the interim results and other documentation must
be made available to the Network Steering Committee, the Network Oversight Board,
and the NIDA Program Official for review and concurrence prior to closure. 
Explicit statistical guidelines for early closure should be specified in the
protocol in order to facilitate these decisions.

-  To submit annual progress reports, including a performance report on each
affiliated CTP, to the NIDA program official. RRTC funding is contingent on
progress, including collaborative contributions and satisfactory patient accrual.

-  To publish major findings in a timely manner, in accordance with procedures
established by the Network Steering Committee.  Publication or oral presentation
of work done under this agreement requires acknowledgement of NIDA support. RRTCs
must agree not to report data prior to collaborative reporting.

The responsibilities of the RRTC towards the CTPs include:

-  Providing CTPs with hardware, software, and data collection staff.  A data
management information system will be established in every CTP to collect intake,
in-treatment and outcome data for all study participants, as well as for a sample
of all patients entering the CTP.  Other descriptive program data will be
collected to characterize each CTP.

-  Providing CTPs with additional therapists, counselors, physicians, physicians'
assistants, nurses, and other staff as needed for the CTP to carry out the
research treatments.  Staff selections will be made by the CTP with the
concurrence of the RRTC.

-  Providing a management and committee structure for the Node which ensures CTP
participation in the planning and implementation of the research.

-  Providing training and supervision of the therapeutic and medical staff who
are conducting the research treatments for each study.

-  Providing data quality assurance and quality control for all studies.

Functions of the RRTCs will include activities such as collection, processing and
analysis of data, reporting to NIDA on the progress of studies, writing papers
for publication, establishing and implementing research procedure and protocol
training for CTP staff involved in studies, scoring instruments, monitoring
compliance with research protocols and participating in committee meetings as
defined above.

An RRTC will be responsible for research project coordination, in conjunction
with its CTPs, when serving as Lead Node on a specific project.  These
responsibilities include coordinating the training of therapists and counselors,
providing training regarding all other aspects of the research, and assuring that
the project is implemented according to the specifications of the final research
protocol. Responsibilities also include executive secretariat functions such as
organization of necessary meetings and conference calls, developing meeting
agendas, taking minutes of sessions, photocopying and distributing materials to
the other RRTCs and NIDA, and preparation of reports to the NIDA Program
Official.

C.  Community Treatment Programs (CTPs).  Each CTP must have a history of
providing quality treatment, in addition to the capability for and interest in
participating in controlled clinical trials and practice research.  CTP
responsibilities include:

-  Agreeing to participate in controlled clinical trials in which either its
primary RRTC or another RRTC has the lead, including randomization methods for
assignment of patients to experimental or control groups, or randomization of
therapists to different conditions;

-  Recruiting adequate numbers of patients required for specific studies;

-  Agreeing to provide routine clinical care to patients participating in
protocols;

-  Agreeing to provide experimental/standard care in accord with approved
research protocols;

-  Providing HIV risk reduction counseling and HIV testing;

-  Maintaining patient records required for each protocol;

-  Collecting clinical and laboratory data, including biological specimens when
indicated;

-  Cooperating with quality control activities of the CTN and adhering to
guidelines set by the RRTC, the Steering Committee, and NIDA;

-  Participating in the decision-making process concerning trials to be run in
the Node with which the CTP is associated, including selection of treatments to
be tested and, as appropriate, study designs, including types of subjects to be
recruited;

-  Agreeing not to report data prior to collaborative reporting;

-  Agreeing to periodic on-site audits by representatives of its RRTC, NIDA, or
a NIDA designee for use of investigational drugs, compliance with regulations for
IRB approval or informed consent (compliance with 45 CFR 46), compliance with
protocol specifications, quality control and accuracy of data recording, and
completeness of reporting of adverse drug reactions.

D.  Network Steering Committee.  The Network Steering Committee (or, simply,
Steering Committee) will constitute the primary governing body of the Network. 
It will consist of the principal investigators of each RRTC, representatives from
community treatment sites, and two NIDA collaborating scientists. This group will
direct the research conducted in the Clinical Trials Network, develop policies
and procedures for development of protocols within the network, act upon
concepts/protocols submitted by Nodes, determine protocols to be implemented
subject to Network Oversight Board review and NIDA approval, coordinate the
implementation of studies across the network, monitor progress, guide data
analysis and interpretation of results, and oversee communications within the
Network as well as with the greater scientific community and the public.

The Steering Committee will also establish training standards and procedures for
therapists in the Clinical Trials Network to assure comparability across sites
in delivery of experimental and comparison treatments.  It will also be
responsible for review and approval of training curricula for treatments that are
ready for dissemination beyond the CTN.  The Steering Committee will oversee
development of measurement tools for use in the CTN.  Core baseline and follow-up
batteries will be established for both program- and patient-level data to be
gathered in all treatment sites throughout the CTN.  The former will include
measures of program orientation, organization, structure, financing,
counselor/therapist characteristics and techniques, and related elements.  The
latter will include intake, outcome and follow-up measures for all patients
enrolled in studies as well as a sample of all admissions to the treatment
programs.  Measures specific to particular clinical trials will be subject to
approval of the Steering Committee.  It will also develop policies on data
sharing, on access to materials and data, including making data available beyond
the Network in a timely manner, and on publication authorship.  Publication
policies will be written and authorship decided using procedures developed and
approved by the Steering Committee.  All publications, whether from a single Node
or multiple Nodes, will be submitted to the Steering Committee for review and
approval.

All major scientific decisions will be determined by majority vote of the
Steering Committee.  All participating RRTCs must agree to abide by the study
designs and policies approved by the Steering Committee, both for studies
spanning multiple Nodes and studies conducted within a single Node.  It is
important to note that research to be undertaken within the CTN is not limited
to research concepts contained within awardees applications, but will be
determined by the Steering Committee based on input from the Nodes and subject
to the approval of the external Network Oversight Board and NIDA.  Future
research must be within and consistent with the scientific objectives of the RFA.

The Steering Committee, by majority vote, will select a Chair from among the
Principal Investigators.  It is anticipated that the Steering Committee will
establish subcommittees and workgroups to assist it in carrying out its
functions.  The Steering Committee may meet up to six times during the first
year, and will meet up to four times per year thereafter, usually in the
Washington, D.C. area.  Applicants should include budgets for travel to these
Steering Committee meetings and subcommittee/workgroup meetings in their
applications and should assure that adequate provisions are made to allow
Principal Investigators and CTP representatives to participate fully in
activities of the Steering Committee and its subcommittees/workgroups.

There will also be a Network Oversight Board, Data and Safety Monitoring Board,
and Administrative Coordinating Center established by NIDA.  These components are
described below.

E.  Network Oversight Board.  The Network Oversight Board serves as an
independent expert board, appointed by and reporting to the Director of NIDA,
that oversees all activities conducted under the CTN.  The Oversight Board will
advise the NIDA director regarding the programmatic advisability of proceeding
with studies proposed by the Network Steering Committee and will assist the
Institute by reviewing and approving final protocols of and major modifications
to studies.  Board membership may be supplemented with subject-matter experts for
review of specific protocols as needed.

The major considerations in protocol review will include:  a) strength of the
scientific rationale supporting the study; b) overall impact of the research; c)
significance of the question being proposed; d) avoidance of undesirable
duplication with ongoing clinical trials; e) approach, including appropriateness
and feasibility of study design; f) satisfactory projected accrual rate and
follow-up period; g) patient safety; h) compliance with NIH and the federal
regulatory requirements; i) adequacy of data management; and j) appropriateness
of patient/participant selection, evaluation, assessment of toxicity where
applicable, response to intervention, and follow-up.

F.  Data and Safety Monitoring Board (DSMB).  The DSMB is an independent expert
board appointed by and reporting to the Director of NIDA, that will oversee and
monitor the conduct of the clinical trials to ensure the safety of participants
and the validity and integrity of the data.  The DSMB will also make independent
assessment of treatment effectiveness and whether a trial will continue.  One or
more NIDA staff will serve as non-voting members on the DSMB.

G.  Administrative Coordinating Center (ACC).  It is expected that NIDA will
competitively award a contract to carry out some of the administrative
coordinating functions of the CTN, for example:

-  Coordination of logistical functions of meetings of the Network Steering
Committee, subcommittees, and workgroups, including production and distribution
of committee minutes.  Funds for participant travel to meetings will not be
disbursed by the ACC; applicants should make adequate provision for these funds
in the budgets submitted under the present RFA.

-  Provision of logistical and operational support for the Data and Safety
Monitoring Board.

-  Reproduction and distribution of research materials (including treatment
protocols, training manuals, and instrumentation), and educational materials.

-  Development, reproduction, and distribution of materials publicizing the
activities of the CTN.

-  Monitoring and managing clinical supplies for medication trials.

Transition to an Expanded Network.  It is anticipated that up to 4 Network Nodes
will be funded in FY 1999.  Contingent upon the availability of funds, the
Clinical Trials Network will be expanded in FY 2000 by the addition of up to 15
new Nodes. In this event, those Nodes funded in FY 1999 will have added
responsibilities for ensuring the smooth transition to an expanded Network. In
their deliberations, those Nodes funded in FY 1999 should anticipate the
implications for an expanded Network.  Some implications of expansion include
changing representation of the Steering Committee and its sub-committees,
introduction of new treatment settings and patient profiles, and consideration
of new proposals for clinical trials and research on translation of new
treatments to practice.  Other issues that have implications for the expanded
Network may include, but are not limited to, the following:

-  Identification and prioritization of clinical trials studies to be undertaken
in the CTN.

-  Research on integrating new interventions into standard clinical practice.

-  Identification and development of study instrumentation, with consideration
of cross-Node comparability.

-  Development of protocols for standard treatments.

-  Development of CTN procedures, including those for review of study protocols,
obtaining input from participating treatment providers, training research
counselors/clinicians, and training research interviewers.

In conceptualizing their early studies under the CTN (for which patient accrual
may not commence until or will continue into the second year of support), Nodes
funded in FY 1999 will need to take into account the implications of expansion
of the CTN for study design and implementation.

SPECIAL REQUIREMENTS

To promote the development of a collaborative program among award recipients, a
number of issues need to be addressed in applications as discussed under
Application Procedures, below.  Applicants should document their ability to
recruit a sufficient number of participants, and should demonstrate their ability
and willingness to work cooperatively with NIDA, other awardees, and CTPs, and
to follow common protocols.

The following terms and conditions will be incorporated into the award statement
and provided to the Principal Investigator(s) as well as the institutional
official at the time of award.

Terms and Conditions of Award

These special Terms of Award are in addition to and not in lieu of otherwise
applicable OMB administrative guidelines, HHS Grant Administration Regulations
at 45 CFR Parts 74 and 92, and other HHS, and NIH Grant Administration policy
statements.

The administrative and funding instrument used for this program is a cooperative
agreement, an "assistance" mechanism (rather than an "acquisition" mechanism) in
which a substantial NIH scientific and/or programmatic involvement with the
awardee is anticipated during 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 awardee(s) for the
project as a whole, although specific tasks and activities in carrying out the
studies will be shared among the awardees and the NIDA Project Scientists.

1. Awardee Rights and Responsibilities

Awardees have primary responsibilities to define objectives and approaches, and
to plan, conduct, analyze, and publish results, interpretations, and conclusions
of their studies in collaboration with other awardees, and with assistance from
NIDA Collaborating Scientists.  Awardees shall participate in the Steering
Committee and abide by decisions of the Steering Committee.  Awardees shall
develop research protocols in conjunction with their CTPs and other awardees and
submit them for approval by the Steering Committee.  Awardees shall take lead
responsibility for implementation of selected protocols as determined by the
Steering Committee, subject to approval of the Network Oversight Board, and shall
participate in additional protocols that are under the leadership of other Nodes. 
Implementation of protocols shall be in accord with Steering Committee policies
and procedures, including policies and procedures pertaining to instrumentation,
data collection, data and safety monitoring, and publication.  Awardees shall
conduct research in partnership with CTPs; assure quality of care; assure that
research findings and adverse events are communicated to research partners and
to NIDA; and assure that treatment is delivered in accordance with established
protocols.

Awardee will retain custody of primary rights to their data developed under the
award, subject to rules formulated by the Steering Committee, and government
rights of access consistent with current DHHS, PHS, and NIH policies.

NIDA Staff Responsibilities

NIDA Collaborating Scientists with expertise in behavioral therapies development,
medications development, and practice research will help to identify research
questions that will have fundamental and timely significance regarding effective
treatment for drug abuse and addiction.  They may cooperate with awardees in
adjustments of protocols and preparation of reports of trial results.  In
instances where significant involvement in the design of trials and/or analysis
of results has occurred, the NIDA Collaborating scientists may cooperate with
awardees as co-authors in preparing publications of data resulting from the
trials.  In this regard, they will be subject to the publication/authorship
policies governing all participants.  In addition, publications involving NIDA
staff require internal clearances.

Two NIDA Collaborating Scientists will be voting members of the Steering
Committee, but will not hold the position of chair.  They will participate in the
development of instrumentation, development of study plans, in quality control,
and in coordination of projects, but will not participate in activities that
directly involve direct assessment, clinical testing, or treatment of human
subjects

The Director, NIDA will appoint an independent Network Oversight Board which will
oversee all research conducted under the CTN, review and approve protocols, and
report to the Director, NIDA.

The Director, NIDA will appoint an independent Data and Safety Monitoring Board,
which will oversee and monitor the conduct of the clinical trials to ensure the
safety of participants and the validity and integrity of the data.  The DSMB will
also make independent assessments of treatment effectiveness and whether a trial
will continue.  One or more NIDA staff will serve as non-voting members on the
DSMB.

A NIDA Program Official, who will not participate in the research, publications,
or Steering Committee, will be responsible for the oversight of each cooperative
agreement.  The Program Official carries primary responsibility for (1) periodic
review and approval of the progress of the protocols in relation to their stated
objectives and (2) making recommendations regarding continuance of the program. 
The NIDA Program Official will be responsible for monitoring the conduct of the
project and overseeing RRTCs.  The Program Official will receive all required
progress reports and determine that satisfactory progress is being made.  This
person also works collaboratively with the Grants Management Specialist to assure
high quality business management of the program, including the most effective use
of Federal financial assistance provided through this cooperative agreement.

NIDA will provide administrative coordination through a separate Administrative
Coordinating Center contract, under supervision of a NIDA project officer.

3. Collaborative Responsibilities

Protocol Development and Implementation.  The protocol is a document mutually
acceptable to the research Node(s), the Steering Committee, the Network Oversight
Board, and NIDA. Communication at the various stages of development is essential.
NIDA Collaborating Scientists will assist the Node PIs in protocol design as
appropriate by providing information regarding therapies that are ready for
testing within the CTN. NIDA will also comment on the scientific rationale,
programmatic relevance, priority, design, statistical requirements, and
implementation of proposed studies.  For medications trials, NIDA Collaborating
Scientists will also provide information regarding:  a) relevant preclinical
toxicology, pharmacokinetic and pharmacodynamic data on investigational agents;
b) availability of investigational agents, c) feasibility and appropriateness of
the medications for testing in community-based settings; and d) therapies and
discoveries from basic research in other NIDA-funded programs that may be ready
for clinical trials.

Protocol concepts are submitted by Nodes to the Steering Committee.  Approved
concepts are developed as formal proposals by collaborating Nodes and submitted
to the Steering Committee.  Protocols approved by the Steering Committee are
submitted to the Network Oversight Board for review and recommendation to the
Director, NIDA.  The Steering Committee will constitute the primary governing
body of the Network.  It will consist of the principal investigators of each
RRTC, representatives from community treatment sites, and two NIDA collaborating
scientists. This group will direct the research conducted in the Clinical Trials
Network, develop policies and procedures for development of protocols within the
network, act upon concepts/protocols submitted by Nodes, determine protocols to
be implemented subject to Network Oversight Board review and NIDA approval,
coordinate the implementation of studies across the network, monitor progress,
guide data analysis and interpretation of results, and oversee communications
within the Network as well as with the greater scientific community and the
public.

The Steering Committee will also establish training standards and procedures for
therapists in the Clinical Trials Network to assure comparability across sites
in delivery of experimental and comparison treatments.  It will also be
responsible for review and approval of training curricula for treatments that are
ready for dissemination beyond the CTN.  The Steering Committee will oversee
development of measurement tools for use in the CTN.  Core baseline and follow-up
batteries will be established for both program- and patient-level data to be
gathered in all treatment sites throughout the CTN.  The former will include
measures of program orientation, organization, structure, financing,
counselor/therapist characteristics and techniques, and related elements.  The
latter will include intake, outcome and follow-up measures for all patients
enrolled in studies as well as a sample of all admissions to the treatment
programs.  Measures specific to particular clinical trials will be subject to
approval of the Steering Committee.  It will also develop policies on data
sharing, on access to materials and data, including making data available beyond
the Network in a timely manner, and on publication authorship.  Publication
policies will be written and authorship decided using procedures developed and
approved by the Steering Committee.  All publications, whether from a single Node
or multiple Nodes, will be submitted to the Steering Committee for review and
approval.

All major scientific decisions will be determined by majority vote of the
Steering Committee.  All participating RRTCs must agree to abide by the study
designs and policies approved by the Steering Committee, both for studies
spanning multiple Nodes and studies conducted within a single Node.  It is
important to note that research to be undertaken within the CTN is not limited
to research concepts contained within awardees applications, but will be
determined by the Steering Committee based on input from the Nodes and subject
to the approval of the external Network Oversight Board and NIDA.  Future
research must be within and consistent with the scientific objectives of the RFA.

The Steering Committee, by majority vote, will select a Chair from among the
Principal Investigators.  It is anticipated that the Steering Committee will
establish subcommittees and workgroups to assist it in carrying out its
functions.  The Steering Committee may meet up to six times during the first
year, and will meet up to four times per year thereafter, usually in the
Washington, D.C. area.  Applicants should include budgets for travel to these
Steering Committee meetings and subcommittee/workgroup meetings in their
applications and should assure that adequate provisions are made to allow
Principal Investigators and CTP representatives to participate fully in
activities of the Steering Committee and its subcommittees/workgroups.

Data Management, Analysis and Access.  Data generated are the property of the
awardee. However, the RRTC must provide NIDA with access to all data generated
under this award.  Data must be shared upon request with the Steering Committee,
subcommittees reporting to the Steering Committee, and the Data and Safety
Monitoring Board.  Data must also be available for external monitoring if
required by NIDA's agreements with other federal agencies, such as FDA and by
NIDA agreements with pharmaceutical companies for co-development of
investigational agents.

In addition, as the CTN is intended to become a national resource, Nodes must be
prepared to share their data widely.  Thus, each proposing RRTC should include
explicit indications of how they will make their data available for broad use and
on what timetable.  The awardee will provide for data sharing consistent with its
data sharing plan, as approved by NIDA.

Quality Control and Monitoring.  For medication trials, the IND holder is
responsible for the study quality control and monitoring.  If NIDA is the IND
holder, additional NIDA medications development staff, in conjunction with the
Steering Committee, will review quality control and monitoring procedures of the
RRTCs including the on-site auditing program for consistency with Good Clinical
Practice (GCP) and procedures established by the Steering Committee for awardees
conducting clinical trials.

Investigational Drug Management.  For medications trials, NIDA Collaborating
Scientists, in conjunction with the Steering Committee, will advise investigators
of specific requirements and changes in requirements concerning investigational
drug management that the FDA may mandate.

4. Organizational Changes

Certain Node organizational changes must have the prior written approval of NIDA.
These include changes in key personnel and the addition or deletion of CTPs.

5. Federally Mandated Regulatory Requirements

Each RRTC will establish mechanisms to meet Department of Health and Human
Services (DHHS)/Public Health Service (PHS) regulations regarding the protection
of human subjects and regarding FDA requirements for the conduct of research
using investigational agents.

Each RRTC must be able to demonstrate that each protocol, amendment, and informed
consent document is approved by the responsible IRB prior to patient entry and
at least annually thereafter, as appropriate for the degree of risk of the
protocol as stipulated by 45 CFR 46.

6. Program Review

In addition to the standard NIH requirement for submission of annual progress
reports, awardees will be required to submit quarterly reports on protocol
progress. NIDA will provide a suggested format for this purpose.  The NIDA
Program Official will review progress through consideration of the quarterly
accrual reports, annual report and program site visits.

The inability of an RRTC to meet the performance requirements and
responsibilities may result in an adjustment of funding, withholding of support,
or suspension or termination of the award.

7. Protocol Closure

NIDA may request that a protocol study be closed for reasons including:  a)
insufficient accrual rate; b) accrual goal met; c) poor protocol performance; d)
patient safety; e) already conclusive study results; and f) emergence of new
information that diminishes the scientific importance of the study question.

NIDA will not permit expenditure of Federal funds or provide investigational
drugs, permit expenditure of NIDA funds, after requesting closure (except for
patients already on study).

8. Arbitration Process

The arbitration procedures will be invoked only when agreement cannot be reached
on programmatic decisions regarding scientific-technical issues that may arise
after the award. An Arbitration Panel will be composed of three members, one
person selected by the Steering Committee (with the NIDA members abstaining) or
by the individual awardee in the event of an individual disagreement, one person
selected by NIDA, and a third person selected by these two members. The
Arbitration Panel will make a recommendation to the Director, NIDA.

The special arbitration procedures described above in no way affect the awardee's
right to appeal an adverse action in accordance with PHS regulations at 42 CFR
Part 50, Subpart D, and HHS regulations 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
sub-populations 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 have been 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, available at:
http//grants.nih.gov/grants/guide/notice-files/not94-105.html.

Investigators may obtain copies from these sources or from the program staff or
contact person listed below.  Program staff may also provide additional relevant
information concerning the policy.

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 the
following URL address:
https://grants.nih.gov/grants/guide/notice-files/not98-024.html.

LETTER OF INTENT

Prospective applicants are asked to submit, by March 13, 1999, a letter of intent
that includes a descriptive title of the overall proposed research; the name,
address, telephone number, and institution of the Principal Investigator; names
of other key investigators, and their respective institutions; and the number and
title of this RFA in response to which the application may be submitted. 
Although the letter of intent is not required, it is not binding and is not a
factor in the peer review of the application, the information it contains is
helpful in planning for the review of applications.  It allows NIDA staff to
estimate the potential review workload and avoid conflict of interest in the
review.

The letter of intent is to be sent to:

Director
Office of Extramural Program Review
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3158, MSC 9547
Bethesda, MD  20892-9547
Telephone:  (301) 443-2755

APPLICATION PROCEDURES

Pre-Application Meeting

There will be a one-day meeting February 22, 1999 at 10:00 am in the Washington,
D.C. metropolitan area to provide potential applicants with background
information and to answer questions from potential applicants.  Details of the
meeting and a summary of meeting results, that will include NIDA responses to all
questions raised by attendees, will be available upon request.

Applications

The research grant application form PHS 398 (rev. 4/98) is to be used in applying
for these awards.  These forms are available at most institutional offices of
sponsored research and from the Division of Extramural Outreach and Information
Resources, National Institutes of Health, 6701 Rockledge Drive, MSC-7910,
Bethesda, MD 20892-7910, telephone 301/710-0267, email: [email protected].

A suggested format will be sent to any applicant upon request or upon submitting
a letter of intent.  All applicants must obtain and use these additional
instructions for organizing the specific information concerning the RFA
programmatic requirements in the PHS 398.

Materials to Include in the Application

Specific content must be present in the application to document the technical and
scientific merit of the applicant's plan for a Node that will be able to address
the fundamental goals and collaborative nature of the CTN.  This should include:

Vision and Research Goals:

A description of the applicant's understanding of the purpose, goals and
capabilities of the CTN and of how the applicant's participation will contribute
to and enhance their realization.  Applicants should not propose detailed
research protocols, but 2-3 specific examples should be given of research
concepts that could be undertaken that would take advantage of the unique
capabilities of the CTN, including collaboration across Nodes.  The examples
should encompass at least two of the three research areas of the CTN: behavioral
therapies, pharmacological therapies, and practice research.  Such examples might
include discussions of the types of research questions which could be addressed,
research methods that might be used, and patient populations that might be
employed.  Particular emphasis should be placed on how the applicant proposes to
ensure that the RRTC and the CTPs of the Node will work collaboratively at all
levels, and that the Node will be able to work collaboratively with other Nodes
and NIDA in multi-site studies for which it is either the lead Node or a
participating Node.  It should be understood that the concepts given in the
application will not necessarily be implemented in the CTN.  Evidence of current
or previous successful collaborations with community treatment programs and of
participation in successful multi-site trials in collaboration with other
research centers would be desirable.

Clinical Infrastructure:

-  Documentation (including letters from CTP directors) of participation of at
least five CTP's in the first year, with detailed descriptions of their
characteristics, including population characteristics, patient flow, types of
treatment currently delivered, number, characteristics and structure of staff. 
It will be critical to establish the ability of the Node to recruit and retain
sufficient subjects to participate in multiple simultaneous trials, and to bring
the number of participating CTPs to at least ten by the beginning of the second
year of award.

-  Documentation of the capability of the Node to deliver a variety of standard
and experimental interventions, including both medications and behavioral
therapies.  This should include numbers, levels of training and experience of
physicians, physicians' assistants, nurses, pharmacists, therapists, counselors
and other personnel within each CTP and throughout the Node

Training Infrastructure:

-  Documentation of the applicant's plan to develop, implement, and maintain a
framework and procedures for the training and supervision of treatment providers
in the experimental and standard interventions that will be utilized in the CTN,
and to coordinate training across Nodes when acting as a lead Node.

Research Infrastructure:

-  The RRTC should document thoroughly its ability to conduct and oversee the
kinds of research to be conducted in the Node and broader Network.  This would
include clear description and documentation of prior research activities and
experience.

-  Documentation of the applicant's proposed procedures for design of studies,
development of protocols, collection, quality control, and protection of
baseline, experimental, and follow-up data within the Node and across Nodes (when
acting as a lead Node), monitoring for and reporting of adverse events,
statistical analysis of data, and reporting of findings.

-  Documentation of how the applicant proposes to make its data available for
broad use beyond the CTN and on what timetable.

-  Documentation of participation of personnel with requisite expertise in
clinical trials, practice research, statistical analysis, and other relevant
areas.

Administrative Infrastructure:

-  Documentation of the applicant's plans for coordination of activities and
communications within the applicant's Node, between the applicant's Node and
other Nodes, and between the applicant's Node and the central CTN structures
(such as the Steering Committee).  Plans for data management and information
management systems should be specified, both within the Node (encompassing all
of the Node's CTPs) and across Nodes (e.g., as the lead Node in a multi-Node
study).  Proposed within-Node committee structures should be given.

In each of these areas, it is crucial that the applicant specify how the
treatment providers will function in true partnership with the RRTC in terms of
study origination, design, execution and administration.  Applicants should
anticipate potential problems and challenges that may arise in this process, and
propose mechanisms for collaborative resolution among the Node participants.  The
NIH policy regarding consortium agreements must be considered in describing the
relationship between the RRTC and the CTPs.

For purposes of budget preparation, the applicant should assume that during the
first several years of support, each RRTC will take the lead on one clinical
trial and will participate in two additional trials.

Page limits: The total length of the Research Plan, including the CTP
descriptions and research concepts, should not exceed 45 pages.  Descriptions of
CTPs should not exceed two pages per program.  Descriptions of research concepts
should not exceed three pages per concept.  No specific page limits apply to the
Human Subjects, Literature Cited, or Consortium/Contractual Arrangements
sections.

The RFA label available in the PHS 398 (rev. 4/98) application form must be
affixed to the bottom of the face page of the application.  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, MSC-7710
6701 ROCKLEDGE DRIVE, ROOM 1040
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for courier/overnight services)

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

Director
Office of Extramural Program Review
National Institute on Drug Abuse
6001 Executive Blvd., Room 3158, MSC 9547
Bethesda, MD  20892-9547
Telephone: (301)443-2755

Applications must be received by April 13, 1999.  If an application is received
after this 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

Applications will be reviewed by NIDA staff for completeness and programmatic
responsiveness to this RFA; those judged to be non-responsive will be returned
to the applicant without review. Applications that are complete and responsive
to the RFA will be evaluated for scientific and technical merit by an appropriate
peer review group convened in accordance with NIH peer review procedures. As part
of the initial merit review, all applications will receive a written critique. 
Those applications deemed to have the highest scientific merit, generally the top
half of applications under review, will be discussed, assigned priority score,
and receive a second level review by the National Advisory Council on Drug Abuse.

Applications will be reviewed for scientific and technical merit using the
following criteria. Applicants should note that the criteria incorporate
consideration of the quality and feasibility of the proposed activities as well
as consideration of past performance as an indicant of the likelihood of
successfully completing the planned work. Reviewers will address each of the
following categories, using the provided questions as examples of the types of
information to consider.

Knowledge and Vision.  How well do the applicant and proposed community treatment
programs understand the purpose, goals and capabilities of the CTN and how will
the proposed Node contribute to their realization?  How knowledgeable is the
applicant regarding research advances in drug abuse treatment, existing clinical
practice, and how to transfer research-based therapies into practice?  How
extensive is the applicant's experience in conducting drug abuse treatment
research?  How significant and scientifically sound are the proposed research
concepts?  To what degree will research on the proposed concepts enhance
understanding about how to conduct, enhance, maintain, and transport treatment
interventions?

Overall Utilization of Network: What is the quality of the plans to take
advantage of the unique opportunities of a research network? How likely to be
effective are the proposed development and use of collaborative resources in the
network? To what degree are a network structure and community collaboration
integral to the successful completion of the research?

Overall Administrative Organization: How successful has the applicant
organization been in administrative and scientific management of complex clinical
trials? What aspects of the organizational structure are conducive to effective
management, and how well will they be applied to the Node and the Network? How
clear and feasible are the provisions for making decisions and resolving
conflict? What is the evidence for and quality of the institutional support
available for involvement in the network? To what degree is there evidence of
integration of research, training, and dissemination activities to allow for
effectively and timely accomplishment of each?

Plans for Network-wide Participation: How strong is the history of successful
collaboration with other researchers and research organizations? How well
documented is evidence of on-going research collaborations or evidence of a
foundation for new research ventures? What is the quality of the plans for
collaboration in a complex, cooperative endeavor that may require compromise? How
sophisticated is the application's discussion of potential problems and solutions
in inter-Node coordination and working in a cooperative agreement? Is there
sufficient flexibility for the Node to participate in research involving a
variety of behavioral and medication therapies and practice research? How well
are issues related to proprietary concerns addressed?

Plans for Within-Node Activities: How strong is the history of successful
collaboration in research, consultation, training, and joint initiative
development with community-based treatment providers? How well documented are
successful, on-going relationships with community providers? How strong is the
foundation for new relationships? Are plans for appropriate administrative
mechanisms (e.g., contracts) in place and how feasible are they? How
sophisticated is the application's discussion of potential problems and solutions
in working with community providers? How much capacity for conducting needed
activities within the Node is evidenced (e.g., resources at the CTPs and RRTC)?
How congruent are the research concepts discussed with levels of access to
patients, anticipated retention rates, and community resources? How significant
are the clinical issues that can be addressed in the Node?

How well developed is the capacity for delivery and monitoring of clinical
interventions? What is the evidence of plans for productive interaction of RRTC
staff with CPT staff and use of their ideas?

Technical Capacity for Training: How strong is the history of developing training
materials and conducting training? To what degree is specific expertise in
training and dissemination of information to various audiences present? What is
the quality of specific plans for conducting, monitoring, and evaluating training
activities? How well developed are the plans for dissemination of results?

Data Management Plans: How strong are the plans for collecting, maintaining,
monitoring, and analyzing data, including consideration of missing data? How well
developed are the plans for assuring data integrity? How sophisticated are the
data-related resources? To what degree does the application reflect an
appreciation of potential problems related to data sharing and collection? Is
there a history of successful data management at the applicant organization? Are
there appropriate plans for releasing data to investigators outside the CTN in
a timely fashion?

Key Personnel: How strongly do the research experience, administrative
experience, and other qualifications of the Principal Investigator and other key
personnel demonstrate the capacity to plan and conduct collaborative clinical and
practice research? How well developed is a decision making plan for selection of
and allocation of personnel resources in the face of changing needs within the
network? What does the team's record of productivity suggest about the importance
of the findings that will be produced from the research? How strongly does the
record of key personnel suggest adequate expertise and flexibility to conduct
research on drug abuse treatment efficacy and effectiveness for both behavioral
and medications trials? How much expertise in training and dissemination is
available? To what degree are the Principal Investigator and staff able to devote
an adequate amount of time to carry out the work involved in the Clinical Trials
Network? How much clinical expertise is available to the Node?

Budget: How appropriate are the budget estimates for the work proposed
(recognizing that much of the work is yet to be determined)? How well is the
budget justified? How appropriate are plans for budgetary control, oversight, and
decision making?

Plans for the appropriate inclusion of women, minorities, and children will also
be evaluated.

AWARD CRITERIA

Applications recommended for further consideration by the National Advisory
Council on Drug Abuse will be considered for funding based upon:  (a) scientific
and technical merit; (b) program balance, including in this instance, sufficient
compatibility of features to make a successful collaborative study a reasonable
likelihood and balance of focus on behavioral therapies, medications, and
practice research; (c) geographic location of applicant organization; and (d)
availability of funds.  An application will not be funded until a site visit has
taken place.

SCHEDULE

Letter of Intent Receipt Date:  March 13, 1999
Application Receipt Date:       April 13, 1999
Scientific Review Date:         July/August 1999
Council Meeting Date:           September 1999
Earliest Award Date:            September 1999

INQUIRIES

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

Direct inquiries regarding programmatic issues to:

Jack D. Blaine, M.D.
Division of Clinical and Services Research
National Institute on Drug Abuse
6001 Executive Boulevard
Bethesda, MD  20892-99563
Telephone:  (301) 443-0107
FAX:  (301) 443-8674
Email:  [email protected]

Betty Tai, Ph.D.
Medications Development Division
National Institute on Drug Abuse
6001 Executive Boulevard, MSC 9551
Bethesda, MD  20892-9551
Telephone:  (301) 443-2397
FAX:  (301) 443-2599
Email:  [email protected]

Direct inquiries regarding fiscal matters to:

Gary Fleming, J.D., M.A.
Grants Management Branch
National Institute on Drug Abuse
6001 Executive Boulevard
Bethesda, MD  20892-9541
Telephone:  (301) 443-6710
Email:  [email protected]

AUTHORITY AND REGULATIONS

This program is described in the catalog of Federal Domestic Assistance No.
93.279.  Awards are made under the authority 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 grant policies and Federal Regulations 42 CFR
Part 52 and 45 CFR Parts 74 and 92.  This program is not subject to the
intergovernmental review requirements of Executive Order 122372 or Health Systems
Agency Review.

The Public Health Service strongly encourages all grant 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 of 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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