NATIONAL DRUG ABUSE TREATMENT CLINICAL TRIALS NETWORK
Release Date: December 20, 1999
RFA: DA-00-002
National Institute on Drug Abuse
Letter of Intent Receipt Date: February 17, 2000
Application Receipt Date: March 16, 2000
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). CTN research is
carried out in community-based treatment settings, in collaboration with
other awardees and with NIDA. Each awardee functions 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
consists of multiple NODEs, and each NODE works in concert with other NODEs
and NIDA to conduct multi-site 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 and
efficacious treatments are successfully adopted. Studies to be conducted will
span multiple sites engaging diverse patient populations in dispersed
geographical regions. As a cooperative agreement, there is substantial NIDA
involvement in the management and administration of the CTN, including
determining which trials are implemented through the Network.
The CTN, with its core of CTPs engaging diverse populations, is also designed
to provide a much-needed vehicle to recruit subjects for studies on such
related topics as the medical consequences of long-term drug use and the
genetics of vulnerability to addiction. Although these studies might use the
CTN as a research platform, the studies themselves would be funded through
separate research grants.
This Request for Applications (RFA) is a second issue with the intention to
develop a geographically diverse and encompassing national Drug Abuse
Treatment Clinical Trials Network. In 1999, five Awards were made to
Northwest NODE, Health Science University of Oregon; Pacific Region NODE-
University of California at Los Angeles; Southern New England NODE, Yale
University; Delaware Valley NODE, University of Pennsylvania; and Mid
Atlantic NODE, Johns Hopkins University.
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 at
http://odphp.osophs.dhhs.gov/pubs/hp2000.
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 1) the objective to bridge the gap of
research to practice, 2) the complexity of the proposed infrastructure and
operation, and 3) the need for multi-site collaboration, it is important for
the Principal Investigators to commit a minimum of 50% time to CTN and to
document a substantial history of leadership in complex multi-site clinical
trials research and an extensive research publication record.
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 National Institutes of Health
(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 studies to be funded
under cooperative agreement(s) are discussed in this document under the
section "Terms and Conditions of Award." Potential applicants are encouraged
to review definitions of key terms used throughout this announcement.
All policies and requirements that govern the grant program of the PHS and
NIH apply.
FUNDS AVAILABLE
NIDA has set aside $11 million to support total costs of establishing
additional CTN NODEs in FY 2000. 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 five awards under this RFA for
project periods of up to 5 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 previous 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
The CTN has been established and will continue to grow to meet two major
research-related needs. First, a clinical trials research infrastructure is
needed to test the effectiveness and usefulness of new and improved
treatments in community-based treatment 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 treatments proven in community treatment settings ready
for adoption into clinical practice.
Research has provided substantial evidence to support 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,
as is the case for other illnesses, the treatment of addiction can be
improved through advances in research on medications and behavioral treatment
approaches. Although considerable research has been directed toward
continuous improvement in the quality of treatment alternatives, the CTN is
designed to accelerate significantly both the pace of treatment research and
its application in 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. For example, in recent years this research
effort has yielded an array 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 now 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 determine how 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 tested an array of both new and existing
medications for specific applications, and some are now ready to test under
controlled conditions 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 new agents after FDA
approval.
Definitions of CTN Organizations and Functions
Clinical Trials Network (CTN). A collaborative group of geographically
diverse Regional Research NODEs working collaboratively with NIDA to conduct
multi-site and cross-regional (nationwide) clinical trials research on
promising behavioral, pharmacological, or integrated drug abuse treatments.
NODE. A NODE is the functional unit within the CTN. The NODE consists of the
Regional Research and Training Center (RRTC) and its affiliated Community
Treatment Programs (CTPs). The RRTC serves as the coordinating core and
arranges a research partnership between the RRTC and CTPs. The CTN will be
comprised of multiple NODEs.
Regional Research and Training Center (RRTC). The RRTC is the recipient of
the cooperative study award. It is one of the two components of a NODE. It
usually resides in the Principal Investigator’s research institute or
organization. The RRTC provides a core of administrative and study
operations services, as well as scientific leadership and management of
clinical trials. The RRTC, acting as the local operation center for a NODE,
has primary responsibility for 1) establishing an infrastructure, 2)
generating a research agenda, 3) providing administration and operations
support, and 4) building partnerships with the CTPs.
- Infrastructure. This includes but is not limited to, 1) arranging and
managing the participation of at least 5 CTPs in the first year, and at least
10 in subsequent years, 2) maintaining scientific and technical personnel for
protocol development and implementation, 3) coordinating intra-NODE
activities, and 4) providing resources for intra-NODE activities.
- Research Agenda. In partnership with its affiliated CTPs, the RRTC
develops and submits research concepts and protocols to the CTN Steering
Committee for review and approval. For each approved protocol, a protocol
specific project team will be established to develop and implement the
research project. It is expected that there will be a Project Director from
the NODE where the research concept and protocol originate. NIDA scientists
will be designated as the scientific and administrative collaborators on the
project team. The Project Director will assume the leadership role for all
aspects of that specific protocol and will serve as the primary liaison to
CTN-wide coordination/support centers as needed.
- Data Acquisition and Management. The RRTC will provide intra-NODE data
acquisition, data management training, and data quality assurance according
to each specific protocol. This data management system must follow the
policies and procedures of the CTN Steering Committee, to 1) monitor adverse
events and report data and other information to the CTN Data and Safety
Monitoring Board (DSMB), and 2) provide timely data to the CTN central data
management center (CDMC) for monitoring protocol progress and for
contributing study specific data to a NIDA central data repository.
- Responsibility toward Affiliated CTPs. The RRTC provides CTPs with 1)
additional therapists, counselors, physicians, physicians' assistants,
nurses, and other staff, as well as the additional training needed for the
CTP, to implement a study protocol; 2) hardware, software, and training to
support CTP-based data acquisition activities. Each RRTC will establish a
data acquisition system to collect intake, in-treatment, and outcome data for
all study participants, according to protocol-specific requirements, and 3)
additional support, such as quality control, to ensure the successful
completion of the scientific goals of a research project. Staff selections
will be made by the CTP with the concurrence of the RRTC.
Community Treatment Programs (CTPs). Drug abuse treatment programs in the
community (typically non-university-based) setting that have a history of
providing quality treatment to large and diverse patient populations,
including women, pre-adolescents and adolescents and have the capability for
and interest in participating in controlled clinical trials. Each CTP must:
- Agree to participate in controlled clinical trials, including randomization
methods for assignment of patients to experimental or control groups or
randomization of therapists to different conditions;
- Recruit adequate numbers (at least 75/year) of patients required for
specific studies;
- Agree to provide routine clinical care to patients participating in
protocols;
- Agree to provide experimental/standard care in accord with approved
research protocols;
- Provide HIV risk reduction counseling and HIV testing;
- Maintain patient records required for each protocol;
- Collect clinical and laboratory data, including biological specimens when
indicated;
- Cooperate with quality control activities of the CTN and adhere to
guidelines set by the RRTC, the Steering Committee, and NIDA;
- Participate in the development of the concept and protocol of trials to be
run in the CTN;
- Agree not to report data prior to collaborative reporting;
- Agree to periodic on-site audits by representatives of its RRTC, NIDA, or a
NIDA designee to ensure 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.
CTN Steering Committee. The Steering Committee will constitute the primary
governing body of the Network. The committee membership consists of the
Principal Investigators of each RRTC, representatives from CTPs, and the NIDA
CTN Director. This group will review and approve the research agenda,
formulate and monitor policies and procedures guiding the research
activities, and oversee communications within the CTN, as well as with the
greater scientific community and the public.
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. 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 Advisory Board and NIDA. Future research
must be within and consistent with the scientific objectives of the RFA.
The Steering Committee, by majority vote, will elect 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 per year, 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.
NIDA Protocol Review Board. An expert board authorized by the Director of
NIDA that will review the final draft of the protocol submitted by the CTN
Steering Committee for scientific and regulatory approval.
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 an 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.
CTN Advisory Board. An independent expert board, appointed by and reporting
to the Director of NIDA, hat oversees all activities conducted under the CTN.
The 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 in prioritizing and approving final
protocols. Protocols will be implemented with the approval of NIDA Director.
Central Data Management Center (CDMC). Data information systems operated by
each NODE are required to implement standards established by the CTN Steering
Committee. Such standards guide the development of the protocol-specific
electronic case report form (eCRF) applications that each NODE is responsible
for implementing at participating CTP sites. The CDMC reports directly to
NIDA, although functions as a resource to the CTN Steering Committee in all
matters related to data management--from study design data acquisition and
analyses to report of study findings and conclusions.
Administrative Coordinating Center (ACC). A contract awarded by NIDA will
support some of the administrative coordinating functions of the CTN to
includes: 1) Coordinating of logistical functions of meetings of the Network
CTN Steering Committee, subcommittees, workgroups, and other boards (e.g.,
the Advisory Board, the DSMB, etc.) and logistical functions including
production and distribution of committee minutes. [NOTE: 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.] 2) Reproducing and distributing research materials
(including treatment protocols, training manuals, and instrumentation) and
educational materials. 3) Developing, reproducing, and distributing
materials publicizing the activities of the CTN. 4) Monitoring and managing
clinical supplies for medication trials. 5) Supporting other operational
needs, such as protocol development, regulatory assistance,
monitoring/quality assurance, trial material distribution, central labs for
analysis of biological fluids, etc.
NIDA Office of CTN. An office within NIDA responsible for the scientific,
administrative, and operational management of the CTN research program funded
by NIDA.
Objectives and Scope
The overall goal of the National Drug Abuse Treatment Clinical Trials Network
is to improve the quality of drug abuse and addiction treatment throughout
the Nation using science as the vehicle.
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 and pharmacological research.
- Ensuring that treatment research in drug abuse and addiction meets the
needs of the wider community, including minorities, women, children,
adolescents, and underserved populations.
- Fostering the collaboration of community treatment practitioners and
treatment researchers, to provide opportunities for bi-directional education
and for the exchange of ideas, information, and values between the treatment
and academic communities.
- Investigating the impact of advances in treatment research on community
level treatment practices.
- Determining the impact of the transport of novel, effective treatments to
the community on the incidence and prevalence of various other illnesses and
conditions, such as blood-borne infections (e.g., HIV and hepatitis).
Characteristics of the CTN
The CTN will provide the Nation a stable, broadly representative
infrastructure for drug abuse treatment research. It is anticipated (pending
availability of funds to continue expanding the CTN) that regional NODEs 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 CTPs will reflect the isparate 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 CTPs, 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 therapies.
Examples of the types of studies appropriate for the CTN include:
- Studies to determine 1) if behavioral therapies found to be efficacious in
smaller-scale studies are effective in community clinics and for different
patient profiles, including adolescents, and how such therapies may be
transported to the community. 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 groups. 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 sero-conversion in both
heroin and cocaine addicts. The CTN 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 pharmacological
interventions for drug dependence treatment in multi-site settings. The
safety and efficacy of the investigational pharmacological agents will be
tested in accordance with FDA regulations, typically by use of double blind,
placebo-controlled or active-controlled designs.
- 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.
- Studies of behavioral interventions aimed at improving compliance with
medication regimens in patients with co-morbid 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.
- Research to develop models for integrating new behavioral interventions
into existing clinical practices.
- Research into the most effective approaches to outreach and risk reduction
counseling. Drug addiction and the spread of HIV/AIDS are intertwined
epidemics, and the CTN will provide a vehicle to help facilitate reduction in
risk behaviors given that all CTPs will provide HIV risk reduction counseling
and offer HIV testing.
- Studies on the efficacy of drug abuse treatment that include among its AIDS
related outcomes: 1) the early treatment of HIV, Hepatitis B and C and
Sexually Transmitted Diseases, 2) the rate of progression to AIDS, and 3) the
prevention and early treatment of co-morbid medical and mental health
conditions associated with HIV/AIDS infection. Studies may incorporate the
most current methodological advances for assessing a) biological and mental
health risks and HIV status, and b) adherence and compliance to
antiretroviral and other medical/mental health therapies.
The CTN, with its core of CTPs 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 collaborate in research
focusing on such issues and to aid in recruitment of appropriate subjects.
The CTN, as a national network of community treatment programs, may provide a
platform to study the factors impacting transmission of knowledge, change of
treatment organizations, and adaptation of new treatments and their adoption
into widespread clinical practice. NIDA encourages researchers to study such
treatment issues at the organizational/program levels under separate research
project grants.
Research will be conducted collaboratively involving NIDA, RRTCs, and CTPs.
The structure of the CTN 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.
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 the
performance of the activity. Under the cooperative agreement, the NIH purpose
is to support and /or coordinate the recipient’s activity by involvement 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 NIDA and its contractors.
This cooperative agreement funding mechanism will require collaboration
between the Director of NIDA’s CTN Unit and the PIs of the CTN NODEs. The
NIDA CTN Unit will assist in coordinating of activities of the CTN as defined
below and will facilitate the exchange of information.
1. Awardee Rights and Responsibilities
Awardees will have primary responsibility for defining the details for the
project within the guidelines described in the Request for Applications and
for performing the scientific activity, and agree to accept close
coordination, cooperation, and participation of NIDA staff in those aspects
of scientific and technical management of the project described in these
terms and conditions. Specifically, awardees have primary responsibilities as
described below.
a. Steering Committee:
The National Drug Abuse Treatment Clinical Trials Network (CTN) shall
establish a Steering Committee that will serve as the governing body of the
CTN. The voting membership of the Steering Committee consists of the
principal investigators of each RRTC, representatives from CTPs, and the NIDA
CTN Director.The Steering Committee, by majority vote, will elect a Chair
from among the Principal Investigators.The Steering Committee will review and
approve the research agenda, formulate and monitor policies and procedures
guiding the research activities, oversee communications within the CTN as
well as with the greater scientific community and the public.
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. Research to be
undertaken within the CTN will be determined by the Steering Committee based
on input from the NODEs and subject to the approval of the external Network
Advisory Board and NIDA. Future research must be within and consistent with
the scientific objectives of the RFA.
The Steering Committee will establish bylaws and standard operating
procedures to govern all aspects of the CTN including, but not limited to,
protocol design and development, protocol review and approval, study
operations and standards, data acquisition and management, and data analysis
and publication. The Steering Committee will also establish CTN performance
goals and standards and monitor progress throughout the life of the CTN and
its research projects.
It is anticipated that the Steering Committee will establish subcommittees
and workgroups to assist it in carrying out its functions.
b. Bylaws/Operating Procedures
The Steering Chair will be responsible for ensuring that there are well
documented policies and operating procedures guiding all aspects of CTN
activities (e.g. protocol development, review, initiation, conduct, and
clousure, data collection, publication, etc.) and bylaws delineating the
requirements and expectations of collaborating institutions, membership
criteria, and standards of performance, and procedures for removing
institutions due to poor performance.
2. Responsibilities of the CTN Regional Research and Training Center (RRTC):
Generally, Awardees under this agreement have the following rights and
responsibilities as a National Drug Abuse Treatment Clinical Trials Network
(CTN) RRTC:
The RRTC provides a core of administrative and study operations services, as
well as scientific leadership and management of clinical trials. The RRTC,
acting as the local operation center for a NODE, has primary responsibility
for 1) establishing an infrastructure for core functions, 2) generating a
research agenda, 3) providing NODE with administration and operations
support, and 4) building partnerships with the CTPs.
- Infrastructure for core functions This includes but is not limited to 1)
arranging and managing the participation of at least five CTPs in the first
year, and at least ten in subsequent years, 2) maintaining scientific and
technical personnel for protocol development and implementation, 3)
coordinating intra-NODE activities, and 4) providing resources for intra-NODE
activities.
- Research Agenda - In partnership with its affiliated CTPs, the RRTC
develops and submits research concepts and protocols to the CTN Steering
Committee for review and approval. For each approved protocol, a protocol
specific project team will be established to develop and implement the
research project. It is expected that a Project Director will come from the
NODE where the research concept and protocol originate. NIDA Scientists will
be designated as the scientific and programmatic collaborators on the project
team. The Project Director will assume the leadership role for all aspects of
that specific protocol and serves as the primary liaison to CTN-wide
coordination/support centers as needed.
- Data Acquisition and Management - The RRTC will provide intra-NODE data
acquisition, data management training, and data quality assurance according
to each specific protocol. This data management system must follow the
policies and procedures of the CTN Steering Committee, to 1) monitor adverse
events and report data and other information to the CTN Data and Safety
Monitoring Board (DSMB), and 2) provide timely data to the NIDA Clinical
data management center (CDMC) for monitoring protocol progress and for
contributing study specific data to a NIDA central data repository.
- Responsibility towards its affiliated CTPs- The RRTC provides CTPs with 1)
additional therapists, counselors, physicians, physicians' assistants,
nurses, and other staff as well as the additional training needed for the CTP
to implement a study protocol, 2) the hardware, software, and training to
support CTP-based data acquisition activities. Each RRTC will establish a
data acquisition system to collect intake, in-treatment and outcome data for
all study participants, according to protocol-specific requirements, and 3)
additional support, such as quality control to ensure the successful
completion of the scientific goals of a research project. Staff selections
will be made by the CTP with the concurrence of the RRTC.
a. Protocol Development:
The Principal Investigator of a RRTC shall initiate the development of a
trial concept/protocol and expeditiously draft the protocol according to
Steering Committee guidelines for protocol content and format. The Steering
Committee will define and manage the review and approval of RRTC initiated
protocols. Such review will include provisions for NIDA scientific review and
comment, including review by an independent NIDA based CTN Protocol Review
Board. The RRTC will be responsible for providing ancillary information about
the protocol to permit review of the proposed project’s scientific rationale,
feasibility, costs, and compatibility with NIDA research priorities and
existing clinical research programs.
b. Administrative Support:
NIDA will establish separate Administrative Coordinating Center (ACC)
contracts to support some of the administrative coordinating functions of the
CTN. This includes: 1) Coordination of logistical functions of meetings of
the Network CTN Steering Committee, subcommittees, workgroups and other
Boards, e.g. the Advisory Board, the DSMB, etc. and logistic functions
including production and distribution of committee minutes. 2) Reproduction
and distribution of research materials (including treatment protocols,
training manuals, and instrumentation), and educational materials. 3)
Development, reproduction, and distribution of materials publicizing the
activities of the CTN. 4) Monitoring and managing clinical supplies for
medication trials. 5) Supporting other operational needs, such as protocol
development, regulatory assistance, monitoring/quality assurance, trial
material distribution, central labs for analysis of biological fluids, etc.
c. Data Management and Analysis:
The CTN RRTCs will be required to establish clinical data acquisition and
data analysis systems within their Node to gather and analyze data collected
as part of CTN multi-site studies. The RRTC data systems will support data
management activities within the Node and its affiliated Community Treatment
Programs.
Data information systems operated by each NODE are required to implement
standards established by the CTN Steering Committee. Such standards guide the
development of protocol-specific electronic case report form (eCRF)
applications each NODE is responsible for implementing at participating CTP
sites.
NIDA maintains a central Clinical Data Management Center (CDMC) under
separate contract to provide a repository of clinical trial data from all the
CTN NODEs. The CDMC reports directly to NIDA and functions as a resource to
the CTN Steering Committee in matters related to data management, from study
design and data acquisition through study analysis and reporting of study
findings and conclusions. The NIDA CDMC provides guidelines and technical
support on matters related to clinical data management and informatics
activities throughout a clinical trial project.
The RRTC data centers are expected to provide incremental clinical and other
trial performance data to the NIDA CDMC as determined by the CTN Steering
Committee. Each protocol proposed under the CTN will include a data
management plan that defines specific data acquisition methods and tools and
identifies responsibility for data management throughout the trial life
cycle.
The Principal Investigators of RRTCs agree to cooperate with the CDMC by
implementing CTN-wide data standards for collection and analysis of data
generated under the CTN, and to provide the CDMC timely data for purposes of
monitoring the safety and progress of clinical studies conducted under the
CTN. RRTCs agree to provide the CDMC final study data according to schedules
developed and approved by the Steering Committee for individual research
projects conducted through the CTN.
d. Data Rights:
The CTN is intended as a national resource for the advancement of treatment
for addicted individuals and other affected persons. The Awardee of this
agreement acknowledges that NIH has access to any and all data generated
under this cooperative agreement and the Awardee agrees to provide royalty-
free, nonexclusive, and irrevocable license for the government to reproduce,
publish, or otherwise use the material and data derived from research
conducted under this cooperative agreement. Data collected or derived under
this cooperative agreement must be shared upon request with the Steering
Committee, or its designee, for external monitoring pursuant to NIDA
responsibilities under agreements with other government agencies (e.g. Food
and Drug Administration) or commercial pharmaceutical companies where NIDA
may co-develop investigational agents.
e. Quality Control and Monitoring:
For medication trials, the holder of the investigational new drug application
(IND) is primarily responsible for study control and monitoring as defined by
FDA rules and regulations. If, NIDA should hold the IND, the RRTCs will be
subject to additional review by NIDA to ensure adherence to FDA Good Clinical
Practice (GCP). The Awardee agrees to provide material and documentation
needed to assure GCP compliance.
For Investigational Drug Management, NIDA’s regulatory affairs specialists,
under direction of the Steering Committee, will review RRTC operations and
advise Investigators of specific requirements concerning investigational drug
management.
For Laboratory Quality Control and Data Management, the RRTCs agree to
participate in protocol-defined measures to ensure methodological and
analytic guidelines established by NIDA through the Steering Committee are
followed. All RRTC participating laboratories performing analytic studies or
services as part of CTN activities must participate in laboratory and data
quality assurance programs established by NIDA to ensure cross NODEs
standards.
f. Subject Safety/Oversight
The RRTC will develop protocol-specific measures to assure the safety and
protection of the rights of volunteers involved in the clinical studies to be
conducted under this cooperative agreement. The Principal Investigator
assumes and accepts the primary responsibility for ensuring CTN studies are
conducted in compliance with all federal regulations and NIDA policies and
procedures. These include but not limited to, Title 21 CFR 50,56,312, and
Title 45 CFR 46. The RRTTC must be able to demonstrate that each institution
and CTP has a current, approved, Assurance on file with the NIH Office for
the Protection of Research Risks (OPRR), that each protocol and informed
consent is approved by the recognized Institutional Review Board (IRB) prior
to enrollment of subjects in any study; that each investigator has a current
Food and Drug Administration Form 1572 curriculum vitae on file at the RRTC;
and that each subject (or legal representative) has given written informed
consent prior to admission to any study conducted under this cooperative
agreement. The Principal Investigator agrees and assures that adequate
records will be maintained, and that access to these records will be
available, to enable outside monitors to assess compliance with applicable
federal laws and regulations.
g. Unexpected Adverse Experience Reporting:
The Principal Investigator of the RRTC agrees to implement and adhere to an
adverse event tracking system designed by the Steering Committee .
h. Reporting Requirements:
In addition to periodic financial and administrative reports required by NIH
for administration of this cooperative agreement, the Awardee agrees to
furnish the following reports according to the schedule indicated:
Program Operations Reports:
Awardees are required and agree to provide quarterly reports of program
activities to the Steering Committee by the 10th day of the Month following
the end of programmatic quarters (90 days from the date of award). The CTN
Steering Committee will define a recommended format and specify minimum
content for these Program Operations Reports.
Protocol-Specific Reports:
Awardees are required and agree to provide periodic reports of protocol-
specific projects according to the policies and procedures established by the
Steering Committee. At minimum the RRTCs must provide timely enrollment
information in a format and according to a schedule defined by the Steering
Committee. Other protocol-specific reports, such as those needed to monitor
the safety and clinical effectiveness of drugs or other interventions under
investigation will be required to allow the Steering Committee and Data and
Safety Monitoring Board to monitor the research projects undertaken in the
CTN. The Steering Committee will determine the nature, frequency, and content
of reports as part of the protocol review and approval process.
Investigational New Drug (IND) Reports:
Awardees are required and agree to provide reports according to regulations
and guidelines established by the Food and Drug Administration (FDA). Data
and other reports required of IND sponsors will be provided to the Steering
Committee prior to dates established by the Steering Committee.
i. Publication of Data:
Prompt and timely presentation and publication in the scientific literature
of findings resulting from research undertaken in the CTN is strongly
encouraged. The Awardee agrees to acknowledge NIDA support in the
publications and oral presentations resulting from research conducted under
cooperative agreement. Prior to the submission of manuscripts for publication
Awardees agree to provide preprint copies to the Steering Committee according
to policies and procedures the Steering Committee may establish to monitor
the presentation and publication of CTN results.
j. Progress Review
The CTN Steering Committee will establish procedures for monitoring the
performance of the RRTCs and the CTPs participating in research under this
cooperative agreement. Performance metrics, such as budget execution, subject
enrollment, data acquisition and transmission, and study analysis and reports
will be defined to permit NIDA and the Network Oversight Committee a means to
assess progress of the CTN and provide information needed to support future
funding decisions.
The inability of an RRTC to meet performance requirements and
responsibilities defined in these Terms and Conditions, and further
elaborated by the Steering Committee may result in an adjustment of funding,
withholding of support, restriction of funds already awarded, or suspension
or termination of the award.
k. National Meetings:
The Steering Committee may meet up to six (6) times each year. The Principal
Investigator agrees to provide adequate support for participation in CTN
meetings as required by the Steering Committee. The Principal Investigator
agrees to support participation by CTP personnel as required by CTN projects.
l. Conflict of Interest:
The Steering Committee will develop and monitor compliance to a Conflict of
Interest Policy applicable to CTN Awardees. The Conflict of Interest Policy
will, at minimum, address issues that may arise through financial ties
between RRTC and CTP participants and the private sectors. The Steering
Committee will collaborate with NIDA in developing the Conflict of Interest
Policy.
m. Protocol Closure:
Throughout the term of the cooperative agreement NIDA may request that a
protocol study be closed for reasons including: 1) insufficient subject
accrual; 2) accrual goal for the protocol is met; 3) poor performance in
conducting the protocol; 4) safety of the subjects in the study; 5)
achievement of conclusive study results; and, 6) emergence of new information
that diminishes the scientific importance of the study question. Financial
support from NIDA through this cooperative agreement will cease upon protocol
closure, except for patients already enrolled in the study.
3. RRTC and CTPs:
a. The RRTC agrees to identify and establish subcontracts with at least ten
community treatment programs (CTPs) to conduct research and training projects
under this cooperative agreement.
Each CTP must:
- Agree to participate in controlled clinical trials, including randomization
methods for assignment of patients to experimental or control groups, or
randomization of therapists to different conditions;
- Recruit adequate numbers (at lease 75/year) of patients required for
specific studies;
- Agree to provide routine clinical care to patients participating in
protocols;
- Agree to provide experimental/standard care in accord with approved
research protocols;
- Provide HIV risk reduction counseling and HIV testing;
- Maintain patient records required for each protocol;
- Collect clinical and laboratory data, including biological specimens when
indicated;
- Cooperate with quality control activities of the CTN and adhering to
guidelines set by the RRTC, the Steering Committee, and NIDA;
- Participate in the development of concept and protocol of trials to be run
in the CTN;
- Agree not to report data prior to collaborative reporting;
- Agree 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.
b. The RRTC shall establish agreements with CTPs that include, at minimum, 1)
a statement of work defining the goals and objectives of the research
projects to be undertaken under this cooperative agreement; 2) a budget for
support of the research projects that clearly identifies the personnel,
equipment, materials, and other costs required to successfully conduct high
quality research in the community treatment program according to the
requirements of specific protocols approved for implementation by the CTN
Steering Committee; and 3) a financial and program reporting requirement,
including access to data and materials, to facilitate CTN program operation
and research project oversight and monitoring.
4. NIDA Staff Responsibilities
Staff of the NIDA will have substantial scientific and programmatic
involvement throughout the life of this cooperative agreement through
technical assistance, and advice and coordination extending beyond normal
program stewardship for grants, as described below and elsewhere.
The role of the NIDA staff as described throughout these Terms and Conditions
is to assist and facilitate, but not to direct the research activities.
Communication and interaction will occur primarily with the scientific
leadership of the RRTC; however, NIDA may also interact directly with the
Directors of any of the collaborating CTPs as needed.
The NIDA CTN Director will be responsible for the normal stewardship and
oversight of the awards as the responsible program official, and will have
primary responsibility for periodic review and approval of RRTC progress. In
addition, the NIDA CTN Director will be substantially involved as described
in these terms and conditions.
a. NIDA's Scientific Role
NIDA Collaborating Scientists (CSs) with expertise in behavioral therapies,
medications development, and practice research will participate in the
development of study plans and protocols, quality assurance and control
activities, and in coordinating projects across scientific disciplines and
CTN nodes. NIDA CSs may initiate or participate in publications in accordance
with established professional and NIH guidelines for authorship. The NIDA CSs
will not, however, have a direct role in assessment, testing, or treatment of
human subjects participating in studies under this cooperative agreement.
The NIDA CTN Director, and/or designated staff, will work closely with the
CTN Steering Committee to assure that the research efforts are consistent
with NIDA’s research objectives and complement other clinical trial
activities supported by NIDA under other means.
NIDA will serve as a resource, and will disseminate information regarding
promising new therapies. NIDA staff will advise the clinical investigators,
as requested or needed, of results from other trials (e.g., adverse
experiences and study termination) that could influence the design,
development, or conduct of clinical trials under this cooperative agreement.
NIDA Protocol Review Board: An expert board authorized by the NIDA Director
that will review the final draft of the protocol submitted by the CTN
Steering Committee for scientific and regulatory approval.
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.
CTN Oversight Advisory Board. An independent expert board, appointed by and
reporting to the Director of NIDA, that oversees all activities conducted
under the CTN. The 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 in Prioritizing and
approving final protocols. Protocols will be implemented with the approval of
NIDA Director.
b. NIDA’s Role in Protocol Review and Approval
In order for a clinical trial to be initiated, the study proposal must be
mutually approved by the CTN Steering Committee and a NIDA Protocol Review
Board. Once notified that a trial is under consideration, NIDA will evaluate
the proposed trial according to NIDA’s treatment research agenda, its
likelihood of timely completion; patient safety; compliance with Federal
regulatory requirements; plans for interim monitoring and final analysis of
results; and resource requirements. NIDA CSs will estimate required
resources associated with the proposed clinical protocol and provide the CTN
Director with advice on proposed resource requirements. The NIDA CTN
Director will return comments and recommendations in writing to the CTN
Steering Committee within 30 days.
In the event a protocol is disapproved, the NIDA CTN Director may work with
the CTN Steering Committee to resolve specific deficiencies or concerns about
the proposed project so that the protocol can be approved and implemented.
Prior to protocol approval as defined above, NIDA will provide no trial
materials or permit expenditure of CTN funds unless and until the proposed
protocol is approved.
Disagreements arising during the protocol approval process may be submitted
to an arbitration panel for resolution. A panel composed of one CTN
designee, one NIDA designee, and a third member with drug abuse clinical
trials expertise chosen by the other two members will be formed to review the
NIDA decision and recommend an appropriate course of action to the Director,
NIDA. These special arbitration procedures in no way affect the Awardee’s
right to appeal an adverse determination in accordance with PHS regulations
at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16.
c. NIDA’s Role During Protocol Conduct
For ongoing clinical trials, a NIDA Medical Officer will monitor the safety
of the treatment being evaluated. Therefore, interim and final reports on
safety for all sponsored clinical trials will be routinely provided to the
NIDA Medical Officer. In addition, for protocols in which NIDA is the IND
sponsor, NIDA will assign medical monitors to review safety and efficacy data
with the protocol statistician and the CTN Data and Safety Monitoring Board.
d. NIDA’s Role in Protocol Closure
The NIDA CTN Director, and/or designated staff, will monitor the progress of
CTN studies by reviewing data and other reports periodically submitted to
NIDA. The independent NIDA Data and Safety Monitoring Board, consisting of
experts from several disciplines, may determine a need to alter, suspend, or
close an ongoing trial due to safety concerns. Additionally, NIDA may deem
it necessary to deny access to further investigational drug supplies and deny
the expenditure of additional NIDA funds (except where volunteers are already
enrolled) if any of the following reasons apply: (1) scientific question no
longer relevant, (2) slow accrual, (3) study will not answer questions
intended in the proposed study plan, or (4) misuse of federal funds. Appeal
of such a decision by the RRTC would proceed in the same manner as an appeal
regarding the disapproval of a protocol prior to opening.
e. NIDA Access to Data
The NIDA CTN Director, and/or designated monitoring staff, shall have access
to all data generated under this cooperative agreement and may periodically
review data recorded on clinical source documents, case report forms, or in
electronic form in a RRTC local database system. Data must be available for
external checking against original source documents as required by NIDA and
Federal regulations pertaining to the responsibility of NIDA as an IND
sponsor. The awardees will retain custody and primary rights to the data
consistent with current HHS, PHS, and NIH policies, including a policy to
provide public access to selected, significant data sets generated with the
use of public funds, within a reasonable period of time after primary
analysis and publication by the CTN.
f. Clinical Trials Agreements
It is expected that for some clinical trials proposed by the CTN Steering
Committee, a pharmaceutical company collaborator will provide investigational
agents for the trials. In order for the CTN, NIDA and the company to
understand their respective responsibilities and rights, a Clinical Trials
Agreement (CTA) will be negotiated and signed by NIDA and the company.
Important terms of the agreement include IND sponsorship, safety and data
monitoring, and access to trial data. Concurrence with the RRTC Principal
Investigator will normally be obtained prior to execution of any final
agreement that deviates significantly from the standard NIDA CTA. In
general, terms in the CTA covering data access and sharing will conform to
policies developed jointly by the CTN leadership and NIDA.
g. NIDA Review of CTN Compliance with Federally Mandated Regulatory
Requirements
The NIDA CTN staff will review applicable regulatory requirements and advise
CTN members of mechanisms to meet; (1) FDA regulations for studies involving
investigational agents, and (2) the NIH Office for Protection from Research
Risks (OPRR) regulations for the protection of human volunteers in clinical
research studies.
h. Review of Performance
The NIDA CTN Project Officers will review the performance of the CTN as a
whole and of individual RRTCs at least annually. Such reviews will include
periodic reviews of the RRTC and its CTP sites for compliance with clinical
and regulatory guidelines and success in achieving any performance standards
established by the Steering Committee. The annual review will be based
primarily on information provided in periodic progress reports defined
elsewhere in these Terms and Conditions, and evaluations of site performance
conducted by the Steering Committee, or its subcommittees.
Insufficient patient accrual, substandard data management or quality,
inadequate progress in executing the research agenda, or noncompliance with
the Terms and Conditions of Award may result in a reduction in budget,
withholding support, suspension, or termination of award.
5. Arbitration
When agreement between an awardee and NIDA staff cannot be reached on
scientific/programmatic issues that may arise after the award, an arbitration
panel will be formed. A panel composed of one CTN designee, one NIDA
designee, and a third member with drug abuse clinical trials expertise chosen
by the other two members will be formed to review the NIDA decision and
recommend an appropriate course of action to the Director, NIDA. These
special arbitration procedures in no way affect the Awardee’s right to appeal
an adverse determination 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/not94-100.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:
http://grants.nih.gov/grants/guide/notice-files/not98-024.html.
LETTER OF INTENT
Prospective applicants are asked to submit by February 17, 2000, 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; the names of other key investigators and their respective
institutions; and the number and title of this RFA in response to which the
application is submitted. Although the letter of intent is not required, 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.
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
Rockville, MD (for express/courier services)
APPLICATION PROCEDURES
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:
Grantsinfo@nih.gov.
SPECIAL INSTRUCTIONS
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.
The use of tables, diagrams, and organizational and flow charts is strongly
encouraged.
APPLICATION PACKAGE
Applicants should include budget estimates and plans for participating in the
CTN, organized around the areas of research planning, core functions, RRTC
and CTP collaboration, and administrative and management plans. Applicants
should not propose detailed research protocols, but provide 2 or 3 specific
examples of research concepts that could be undertaken that are consistent
with the RFA and that would take advantage of the unique capabilities of the
CTN, including collaboration across NODES. The examples should encompass
clinical trials on drug abuse treatment. Such examples might include
discussions of the types of research questions that could be addressed,
research methods that might be used, and patient populations that might be
employed. Particular emphais 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 clinical trials. It should be understood that
the concepts given in the application will not necessarily be implemented in
the CTN. A pplicants must demonstrate access to diverse racial and ethnic
populations through the aggregrate of their proposed community treatment
providers. 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. An
application package should include the following:
Research concepts and planning:
The research plans for the proposed controlled clinical trials should include
descriptions of study design, interventions, and statistical considerations;
access to appropriate patients; procedures for data management, quality
control and follow-up; procedures for monitoring and reporting adverse
events.
Core infrastructure functions:
The plans should document the availability of appropriate expertise within
the RRTC to design, implement, and analyze the results of the proposed
trials.
Description of the infrastructure for core functions, e.g., including but not
limited to:arranging and managing the participation of at least five CTPs in
the first year, and at least ten in subsequent years; maintaining scientific
and technical personnel for protocol development and implementation;
coordinating intra-NODE activities; and providing resources for intra-NODE
activities.
Describe the available resources and personnel for administration of the
NODE. Describe the infrastructure capabilities in research administration,
operational management, protocol development, clinical data information
systems and management of regulatory documents.
The plans should describe the framework and procedures for training and
supervision of treatment providers in the experimental and standard
interventions that will be utilized in the CTN.
RRTC and CTP collaboration:
The application should provide documentation (letters of agreement from CTP
directors) of participation of five or more CTPs in the first year, with
detailed descriptions of each CTP’s characteristics, including patient
population characteristics; patient throughput; types of treatment currently
delivered; and number, characteristics, and structure of staff. It will be
critical for the NODE to recruit and retain sufficient CTPs to participate in
multiple simultaneous trials and to bring the number of participating CTPs to
at least 10 by the second year of award. The ability to do this should be
evident.
An organizational chart to describe the functional structure for involving
appropriate RRTC and CTP personnel in the design and implementation of a
variety of therapies should be provided. An organizational chart and a
description of the RRTC operation should describe the relationship between
the research and administrative functional units within the NODE.
In each of these areas, it is crucial that the applicant describe 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
Administrative and Management Plan
The qualifications and experience of the Principal Investigator must be
described. An individual should be designated as the coordinator for intra-
NODE research activities. His or her qualifications and experience should
also be described. Each application must also demonstrate the ability to
access professionals with the appropriate expertise to design and implement
the proposed interventions and controlled clinical trials.
It is important to establish the Principal Investigator’s ability to
contribute to the scientific agenda and adequate time commitment (a minimum
of 50%) to provide protocol mandated leadership for the clinical trial. The
accrual of geographically diverse CTPs should be evident. 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.
Plans for intra-NODE data management and information management systems
should be specified (encompassing all of the NODE's CTPs). Diagrams and
descriptions of proposed within-NODE committee structures should be given.
Each applicant must demonstrate the ability to train and maintain the
proficiency of CTP personnel to successfully manage treatment and clinical
trials research. This will include training in data management, data
collection, trials monitoring, and implementation of research protocols.
Budget
The applicant should prepare a separate detailed budget for 1) infrastructure
to enable the RRTC to provide core functions for the NODE (e.g., personnel,
facilities, equipment, supplies, training cost, logistic support, travel,
etc.) and; 2) protocol specific costs such as training (of therapist or data
manager), data management, clinical associated expenses, laboratory costs,
monitoring costs, publications costs; and 3) CTP support to conduct the
clinical trials.
Page Limits
The total length of the Research Plan, including the CTP descriptions and
research concepts, administrative and management plan, and budget should not
exceed 45 pages. Descriptions of CTPs should not exceed 2 pages per program.
Descriptions of research concepts should not exceed 3 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 two of the face page of the
application form, and the YES box must be marked. The RFA number must be
typed on label as well.
The sample RFA label is available at:
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to
allow for this change. Please note this is in pdf format.
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 Boulevard, Room 3158, MSC 9547
Bethesda, MD 20892-9547
Rockville, MD 20852 (for courier/overnight services)
Telephone: (301) 443-2755
Applications must be received by March 16, 2000. 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
Upon receipt, applications will be reviewed for completeness by the CSR and
responsiveness by the NIDA. Incomplete and/or non-responsive applications
will be returned to the applicant without further consideration Applications
that are complete and responsive to the RFA will be evaluated for scientific
and technical merit by an appropriate peer review group convened by NIDA. 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 a 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.
Research Plan
Adequate understanding of the scientific agenda of the CTN.
Feasibility of contributing to the goals and enhancing the capability of the
CTN.
Significance of the research concepts proposed and knowledge of state-of-the-
art research designs and methodologies.
Research Infrastructure
Time availability, qualifications, and research experience of the RRTC
Principal Investigator and named scientific leadership, including but not
limited to, previous experience with design, administration, and management
of multi-center clinical trials.
Qualification of key personnel and scientific staff in the areas of proposed
research.
Qualification of staff in providing statistical and data management expertise
for multi-site clinical trials.
Adequacy of the available resources and personnel for administration of the
NODE. Evidence of infrastructure capabilities in research administration,
operational management, protocol development, clinical data information
systems, and management of regulatory documents.
CTPs and RRTC (collaboration)
Previous experience and adequacy of plans for involving CTPs in research and
organizational activities.
Adequacy of RRTC's criteria for selecting community-based treatment programs
(CTPs) that have diverse geographic and population representation, balanced
by the constraints of reasonable management.
Adequacy of the quality and variety of CTP programs and experience of the
program directors. Ability to accrue a demographically diverse patient
population and adequacy of the plan for patient enrollment, and retention, as
well as program evaluation. Ability to accrue patients at an adequate rate
to support multisite clinical trials.
Administrative and management plan
Adequacy of the plans for overall NODE management and operations, including
the structure and mechanism for effective intra-NODE communication and
collaboration.
Previous experience and adequacy of plans for training therapists and
research associates in implementing multi-site clinical trials.
Adequacy of plans for intra-NODE data management, including adequacy of the
plan for incorporating CTN-wide data standards, data collection, analysis,
and site-specific training.
Adequacy of plans for effective interaction and coordination with other NODES
and NIDA.
Budget
Adequacy of budget estimates for 1) infrastructure to enable the RRTC to
provide core functions for the NODE (e.g., personnel, facilities, equipment,
supplies, training costs, logistic support, travel, etc.) and; 2) protocol
specific costs such as training (therapist or data manager), clinical
expenses, laboratory costs, monitoring costs, publications costs; 3) CTP
support to conduct the clinical trials; and 4) adequacy of plans for
budgetary control and oversight.
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; 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: February 17, 2000
Application Receipt Date: March 16, 2000
Scientific Review Date: Summer 2000
Council Meeting Date: September 2000
Earliest Award Date: September 30, 2000
INQUIRIES
Inquiries concerning this RFA are encouraged. The opportunity to clarify any
issues or questions from potential applicants is welcome.
Direct inquiries regarding programmatic issues to:
Betty Tai, Ph.D.
Office of Clinical Trials Network
Division of Treatment Research and Development
National Institute on Drug Abuse
6001 Executive Boulevard, Room 4129, MSC 9551
Bethesda, MD 20892-9551
Telephone: (301) 443-2397
FAX: (301) 443-2599
Email: bt26r@nih.gov
Jack D. Blaine, M.D.
Division of Treatment Research and Development
National Institute on Drug Abuse
6001 Executive Boulevard, Room 4226, MSC 9551
Bethesda, MD 20892-9551
Telephone: (301) 443-0107
FAX: (301) 443-8674
Email: jb167n@nih.gov
Direct inquiries regarding peer review issues to:
Teresa Levitin, Ph.D.
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
FAX: (301) 443-0538
Email: tlevitin@nida.nih.gov
Direct inquiries regarding fiscal matters to:
Gary Fleming, J.D., M.A.
Grants Management Branch
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3131, MSC 9541
Bethesda, MD 20892-9541
Telephone: (301) 443-6710
FAX: (301) 443-6847
Email: gf6s@nih.gov
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.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
|
|
|
|
Department of Health and Human Services (HHS)
|
|
|
|
NIH... Turning Discovery Into Health®
|