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 301/435-0714, 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.


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