THE NATIONAL DRUG ABUSE TREATMENT CLINICAL TRIALS NETWORK

RELEASE DATE:  July 07, 2004

RFA Number:  RFA-DA-05-001 (Reissued as RFA-DA-07-001)

EXPIRATION DATE:  October 15, 2004

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH) 
 (http://www.nih.gov)

COMPONENT OF PARTICIPATING ORGANIZATION:
National Institute on Drug Abuse (NIDA) 
 (http://www.nida.nih.gov)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER:  93.279

LETTER OF INTENT RECEIPT DATE:  September 14, 2004
APPLICATION RECEIPT DATE:  October 14, 2004  

THIS REQUEST FOR APPLICATIONS (RFA) CONTAINS THE FOLLOWING INFORMATION:  

o Purpose of this RFA
o Research Objectives
o Mechanism(s) of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Supplementary Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS RFA 

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). Applications 
from geographic areas not currently well represented in the CTN are 
particularly encouraged. This Request for Applications (RFA) is the fourth 
solicitation for participation in the CTN.  It is intended for both new 
applications and competing continuations. 

As a nation-wide partnership among drug abuse treatment providers, 
researchers, and NIDA staff, the mission of the CTN is to conduct studies of 
behavioral, pharmacological, and integrated behavioral and pharmacological 
treatment interventions in rigorous, multi-site clinical trials to determine 
the effectiveness of these interventions across a broad range of community-
based treatment settings and diverse patient populations.  The CTN 
disseminates and promotes the adoption of proven treatments to physicians, 
providers, their patients, accrediting bodies, educational institutions, 
policy makers and funders to improve the quality of drug abuse treatment 
throughout the country, using science as the vehicle.  

CTN clinical trials are carried out in community-based treatment settings. 
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 clinical trials research. Awardees deliver and test an array of 
both behavioral and pharmacological treatments and determine conditions under 
which novel and efficacious treatments are successfully adopted. Studies 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. 

Current CTN Nodes are located in California, Colorado, Connecticut, Florida, 
Maryland, Massachusetts, Michigan, New Mexico, New York, North Carolina, 
Ohio, Oregon, Pennsylvania, South Carolina, and Washington. NIDA recognizes a 
benefit in a greater geographic distribution of CTN sites as well as a desire 
to encompass more subpopulations of minority groups and to broaden the range 
of treatment providers who work under varying systems of reimbursement and 
organization of care.  By expanding in these areas, greater variety in the 
types of studies conducted and greater confidence in the generalizability of 
those studies will be assured.  Therefore, as noted, one purpose of this 
Request for Applications (RFA) is to expand the geographic distribution of 
CTN sites, and applications are encouraged from investigators in those 
geographic areas without CTN Nodes and where the CTN is not well represented. 
Another purpose is to enable eleven existing Nodes to re-compete to continue 
participation within the CTN for another five years. 

RESEARCH OBJECTIVES 

Background 

The development of the CTN was based, in part, upon a recommendation from the 
National Advisory Council on Drug Abuse and conclusions of the Physicians 
Leadership on National Drug Policy.  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" also 
recommended a national network for drug abuse treatment trials.  Following 
the first NIDA CTN solicitation in 1999, six CTN awards were made to awardees 
in California, Connecticut, New York, Oregon, Maryland, and Pennsylvania. 
After a solicitation in 2000, awards were subsequently made to five 
additional sites in Colorado, Florida, Michigan, Ohio, and South Carolina.  
In 2001 three additional sites were awarded in New York (Long Island), North 
Carolina and Washington. In 2002 there were three additional sites added in 
California, Massachusetts, and New Mexico.  These sites represent a variety 
of treatment traditions that include pharmacological as well as behavioral 
and other psychosocial interventions.  Furthermore, NIDA ensured a wide 
variety of patient populations in the selection of CTN recipients. Women, 
minority groups, and adolescents are well represented.

The CTN is now established and is making progress in achieving its goals of 
(1) providing a clinical trials research infrastructure to test the 
effectiveness and usefulness of new and improved treatments in community-
based treatment settings with diverse patient populations, (2) serving as a 
mechanism for the study of dissemination of new and improved interventions 
into community-based drug treatment settings and (3) providing unique 
opportunities to train clinical researchers. The infrastructure of the CTN is 
available for non-network researchers to use a study platform. A number of 
functional committees to provide governance to the CTN are established, 
protocols for the study of both pharmacological and behavioral interventions 
are currently underway, data management and safety monitoring procedures are 
in place, and new studies are being planned and approved.  Details on the 
status of the CTN initiative may be found on the NIDA web site at: 
http://www.nida.nih.gov/CTN/Index.htm. 

Strong partnerships and bi-directional collaboration between researchers and 
practitioners are an essential and defining characteristic of the CTN.  
Although treatments for drug abuse exist and considerable research has been 
directed toward the improvement of treatment alternatives, most addiction 
treatment research prior to the CTN was conducted primarily in specialized 
research settings.  Through the researcher-practitioner partnership that 
characterizes the CTN, the CTN accelerates the use of research outcomes, the 
pace of research, and its application to community treatment settings by 
conducting large scale multi-site clinical treatment studies in community 
based treatment programs (CTPs).  

Knowledge gained through the CTN is also expected to further the 
dissemination and the adoption of research-based treatments. That is, CTN 
research will not only help determine which treatments should be implemented, 
it will also inform the process of implementation and dissemination to ensure 
the acceptability and sustainability of new approaches

CTN DEFINITIONS, ORGANIZATION, 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 coordinates and arranges a research 
partnership between the RRTC and CTPs. The CTN is comprised of multiple 
Nodes. Activities that occur primarily within a single Node (e.g., hiring of 
staff, RRTC-CTP activities) are called "Intra-Node" activities, as opposed to 
CTN-wide or "Inter-Node" activities such as implementation of protocols 
across one or more Nodes, development of CTN-wide policies, etc.  A "Lead 
Node" is a Node that has primary responsibility for leading a research 
project.

Regional Research and Training Center (RRTC).  The RRTC is the recipient of 
the cooperative agreement award.  It is one of the two components of a Node.  
It typically resides in the Principal Investigator’s research institute or 
organization.  The RRTC provides scientific leadership and design of clinical 
trials. The RRTC has primary responsibility for 1) establishing the 
infrastructure, 2) generating a research agenda in collaboration with the 
CTPs, 3) providing administration and operations support, 4) building 
partnerships with the CTPs, and, 5) collaborating with NIDA and other Nodes 
to develop, implement, and disseminate findings from CTN research projects, 
and 6) working with the CTN Clinical Coordinating Center and Data and 
Biostatistics Center. 

Infrastructure.  Infrastructure refers to the capacity of the RRTC and CTPs 
to 1) arrange and manage collaborative activities of at least five CTPs with 
the RRTC, 2) maintain scientific and technical personnel for protocol 
development and implementation, 3) coordinate intra-Node activities, and 4) 
provide resources for intra-Node activities.  It also refers to the physical 
resources (buildings, clinics, etc.) available. 

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 concept, a protocol specific project 
team is established to develop and implement the research project across the 
CTN. It is expected that there will be a Lead Investigator (LI) from the Node 
where the research concept and protocol originated.  NIDA scientific and 
technical personnel may be designated as collaborators on the project team. 
The LI assumes the leadership role for all aspects of that specific protocol 
and serves as the primary liaison to CTN-wide coordination/support centers as 
needed.  The project team for each CTN research project includes personnel 
and experts across the network from all disciplines required for the 
development and implementation of the project.

Training Agenda: In partnership with the training support for clinical 
researchers the CCTN strongly encourages the RRTC to apply for training 
grants to support physicians, clinical psychologists, post-doctoral 
candidates, and junior faculty.  The CTN provides many opportunities for 
these researchers to gain valuable experience in designing and managing 
multi-site clinical trials.

Administrative and Operations Support. The RRTC ensures appropriate 
administrative and operational support for Node activities. The support must 
ensure adherence to the Terms and Conditions of the Award and the policies 
and procedures of the CTN Steering Committee to: 1) design and develop CTN 
research projects; 2) formulate and conduct project specific training; 3) 
develop patient safety and other regulatory documents to obtain approvals 
needed to implement studies within the Node; and, 4) ensure the quality of 
research within the Node through on-site monitoring at participating clinical 
sites.

Partnership with and Responsibility toward Affiliated CTPs.  The RRTC 
functions as a partner with its associated CTPs.  It provides CTPs with 1) 
support for the CTP Director representing the Node on the Steering Committee, 
2) scientific guidance and mentoring as the RRTC develops research concepts 
for the CTN 3) support for the CTP Director to participate in Special 
Interest Groups, Subcommittee activities and protocol development teams 4) 
support for CTP participation in CTN Blending Meetings.

Community Treatment Programs (CTPs). Drug abuse treatment programs in the 
community setting (typically non-university-based) that have a history of 
providing quality treatment to large and diverse patient populations, 
including women, members of minority groups, and adolescents, and have the 
capability for and interest in participating in controlled clinical trials. 
Working as an equal partner with its RRTC, each CTP must: 

o 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; 

o Screen and recruit adequate numbers of patients required to meet the 
expectation of specific protocols. This frequently requires recruiting one 
patient per week.  

o Agree to provide routine clinical care to patients participating in 
protocols; 

o Agree to provide experimental/standard care in accord with approved 
research protocols; 

o Provide HIV risk reduction counseling and access to HIV testing;

o Provide HCV education and referral for testing and treatment;

o Maintain patient records and other source documents required for each 
protocol; 
 
o Collect clinical and laboratory data, including biological specimens when 
indicated; 

o Cooperate with quality assurance activities of the CTN and adhere to 
guidelines set by the RRTC, the Steering Committee, and NIDA;

o Cooperate with NIDA’s Clinical Coordinating Center and Data and Statistics 
Center; 

o Participate in the development of research concepts and protocols for 
trials to be conducted in the CTN; 

o Agree not to report data prior to collaborative reporting; 

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

Principal Investigator.  The senior scientist named in the grant by the 
applicant institution to lead and manage the activities within the Node.

CTP Director.  The individual designated by the participating community 
treatment program to represent the CTP on the Node. This individual is also 
responsible for the CTP’s obligations to the Lead Investigator during the 
course of a protocol. 

CTN Steering Committee.  The Steering Committee constitutes the primary 
governing body of the Network. The committee membership consists of the 
Principal Investigator and one CTP Director from each Node, two NIDA 
representatives (one of which is the NIDA Director of the Center for Clinical 
Trials Network), one representative from the CTN Clinical Coordinating Center 
and one representative from the CTN Data and Statistics Center. This group 
reviews and approves the research agenda, formulates and monitors policies 
and procedures guiding the research activities, and oversees communications 
within the CTN, as well as with the greater scientific community and the 
public. 

All major network decisions are determined by majority vote of the Steering 
Committee. All participating RRTCs and CTPs 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 are and will be 
determined by the Steering Committee based on input from the Nodes and 
subject to the approval of NIDA. Future research must be within and 
consistent with the scientific objectives of the RFA. 

The Steering Committee uses established subcommittees and workgroups to 
assist it in carrying out its functions. The Steering Committee meets no more 
than four times per year.  Applicants should include costs for travel to 
these Steering Committee meetings and subcommittee/workgroup meetings in 
their applications and should assure that adequate provisions are made to 
allow the Principal Investigator, Node personnel and CTP representatives to 
participate fully in activities of the Steering Committee and its 
subcommittees and workgroups.  http://www.nida.nih.gov/CTN/Index.htm.

NIDA Protocol Review Board.  An independent expert board authorized by the 
Director of NIDA to advise the Director CCTN on scientific and regulatory 
issues.   

Data and Safety Monitoring Board (DSMB).  The DSMB is an independent expert 
board, appointed by and reporting to the Director of CCTN that oversees and 
monitors the conduct of the clinical trials to ensure the safety of 
participants and the validity and integrity of data for each study. The DSMB 
also makes an independent assessment of the interventions under study and 
whether or not any trial undertaken in the CTN will continue. One or more 
NIDA staff serves as non-voting members on the DSMB. 

Data and Statistics Center (DSC). A contract awarded by NIDA to provide 
clinical data information systems as required to implement standards 
established by NIDA and the CTN Steering Committee. Such standards guide 
development and implementation of the protocol-specific electronic case 
report form (eCRF) applications that each Node must implement at 
participating CTP sites. The DSC reports directly to NIDA, although it 
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. 

1)  Provide logistical support for specific trials, e.g. hire research staff, 
provide computer hardware and software to participating CTPs if needed, and 
provide Internet access to participating CTPs if needed.
2)  Assist the Lead Investigator in protocol development with respect to data 
management, design and analysis, and interim analysis plan (if applicable).
3)  Manage all aspects of data collection. 
4)  Analyze data to test primary and secondary study hypotheses.
5)  Monitor trial progress.
6)  Conduct data quality assurance monitoring.
7)  Produce reports for the Data and Safety Monitoring Board (DSMB)
8)  Provide data/facts that will assist NIDA staff with producing Node 
performance reports based on CTN’s performance criteria. 

Clinical Coordinating Center (CCC):  NIDA provides via a contract certain 
resources and common services for CTN clinical trials, including support for 
administrative requirements and oversight functions mandated by NIH.  
Specifically:

1)   Regulatory affairs and Investigational New Drug (IND) filing;
2)   Monitoring for clinical study sites;
3)   Administrative support for protocol development; 
4)   Project management;
5)   Training in Good Clinical Practice (GCP) etc.;
6)   Central pharmacy services for medication packaging and shipping;
7)   Clinical laboratory support.
8)   Coordinate activities (face-to-face meetings and/or conference calls) for 
specific protocols (not core CTN meetings).
9)   Coordinate the distribution of trial supplies, e.g. medication, forms, 
manuals.
10)   Coordinate the distribution of materials with laboratories involved in 
CTN’s clinical trials.
11)    Assist the Lead Investigator in protocol development with respect to 
regulatory, QA and training plans.
12)    Provide training of general clinical research conduct (GRP) and CTN 
protocol common assessment batteries (CAB).
13)    Monitor GCP compliance according to the Quality Assurance Plan defined 
by each Lead Investigator of the protocol. 
14)    Monitor regulatory compliance.
15)    Provide data/facts that will assist NIDA staff with producing Node 
performance reports based on CTN’s performance criteria.  
   
Logistic Support Center (LSC).  A contract awarded by NIDA to support many of 
the administrative and logistic functions of the CTN including: 
1)   Coordinating logistic and operational support for a variety of CTN 
meetings with up to 250 attendees;
2)   Handling all logistics and costs with coordinating over 400 conference 
calls on an as needed basis per year; 
3)   Support for consultants providing NIDA and the CTN grantees with expert 
advice on a variety of topics regarding the Network; 
4)   Preparing publicity, meeting, and protocol related materials as required;
5)   Providing scientific writers/editors to prepare reports, take minutes of 
meetings and conference calls, edit documents; 
6)   Reproducing and distributing research materials, protocol related 
documents, and educational materials;
7)   Creating and maintaining administrative records to support the CTN 
activities; 
8)   Providing translation services for CTN materials in languages other than 
English;
9)   Maintaining a CTN web site; and 
10)   Miscellaneous support services.
 
NOTE:  Funds to support Node personnel travel to meetings will not be 
disbursed by the LSC. Applicants should make adequate provision for these 
funds in the budgets submitted under the present RFA. See the Subsection 
"Budget" in the "APPLICATION PACKAGE" section below for more guidance on this 
issue. 

Center for the Clinical Trials Network (CCTN).  The organization 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: 

o A standard frame of reference in research on drug abuse and development of 
comprehensive drug abuse treatment programs that integrates co-morbid 
medical/mental health conditions (e.g., mental disorders, HIV, Hepatitis B & 
C, tuberculosis, sexually transmitted diseases (STDs) and other blood-borne 
infections.

o Supporting rigorous, multi-site clinical trials of efficacious behavioral, 
pharmacological, and combined behavioral and pharmacological treatment 
interventions in community-based treatment programs to determine 
effectiveness across a broad range of treatment settings and patient 
populations. 

o Encouraging research on effective strategies for transporting science-based 
treatment interventions into clinical practice. 

o Furthering the development of effective treatments by integrating 
behavioral and pharmacological interventions. 

o Ensuring that treatment research in drug abuse and addiction is extended to 
the wider community, such as minorities, women, children, adolescents, and 
underserved populations. 

o Ensuring that treatment research in drug abuse and addiction addresses the 
needs of special populations within the wider community, including court-
involved patients and patients with co-morbid psychiatric or medical 
conditions.

o Fostering the collaboration between community practitioners and treatment 
researchers by providing opportunities for bi-directional education, exchange 
of ideas, information, and values. 

o Investigating the impact of community-based treatment research on community 
treatment practices.

o Exploring the effectiveness of behavioral, pharmacological, and integrated 
behavioral and pharmacological treatment interventions to reduce the 
transmission of HIV and other disease (such as hepatitis B and C or sexually 
transmitted infections) and to enhance adherence to treatment for HIV and 
other disease among drug users.  Additionally, small efficacy trials of 
promising, theoretically grounded behavioral interventions may be conducted. 

This RFA also seeks a broad range of research on disease prevention for drug 
users in treatment including, but not limited to, the following topics.  
o The effectiveness of behavioral and/or pharmacological drug treatment 
modalities in reducing drug-related transmission risks for HIV and other 
disease;
o The effectiveness of drug use relapse prevention programs and other 
enhanced engagement-in-drug-treatment interventions in reducing drug-related 
transmission risks for HIV and other disease;
o The effectiveness of culturally appropriate HIV testing and counseling 
interventions in reducing drug- and sex-related transmission risks among HIV-
positive and HIV-negative drug users in drug treatment settings; 

o The effectiveness of cognitive-behavioral-affective skills building 
interventions in reducing drug-related transmission risks for HIV and sex-
related transmission risks for HIV and other STIs, specifically tailored for 
heterosexual adults or men who have sex with men;

o The effectiveness of developmentally appropriate cognitive-behavioral-
affective skills building interventions in reducing drug- and sex-related 
disease transmission risks among adolescent drug users in treatment; 

o The effectiveness of peer- or family-based interventions in reducing drug 
abuse and drug-related transmission risks among adolescents in drug treatment 
settings;

o The effectiveness of psychiatric treatment (e.g., for depression, anxiety, 
PTSD, ADHD, conduct problems) in reducing drug- and sex-related transmission 
risks among adolescent or adult substance abusers in drug treatment settings; 

o The effectiveness of on-site, antiretroviral therapy adherence/compliance 
counseling for HIV- or HCV-infected drug users in drug treatment;

o The effectiveness of providing comprehensive medical services, or linkage 
to primary care, for HIV-, HCV- or STI-infected drug users in drug treatment.

Characteristics of the CTN

The CTN provides the Nation with a stable and broadly representative platform 
for drug abuse treatment research through regional Nodes distributed 
throughout the country.  Each Node encompasses a substantial geographical 
area and a variety of treatment settings, patient populations, and drug abuse 
problems. The RRTC of each Node must have demonstrated expertise in 
conducting drug abuse treatment research, clinical trials and clinical 
training. Through its associated CTPs, each Node must demonstrate the 
capacity to recruit and treat a broad range of patients, including 
adolescents, women, patients with co-occurring mental disorders, those at 
high risk for HIV infection, members of racial/ethnic groups, and those 
abusing or addicted to various drugs of abuse. All Nodes must demonstrate the 
capacity to deliver and test a variety of both pharmacological and behavioral 
therapies.  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. For the CTN to be maximally 
effective, the CTPs must be partners in the research enterprise by 
participating in research decisions, including selection of research concepts 
to be implemented and decisions concerning protocol design. The CTN has 
completed several protocols, several are actively enrolling participants, and 
more are preparing to initiate enrollment. See listing on the web at 
http://www.nida.nih.gov/CTN/research.html.

As the CTN continues to develop, it is anticipated that CTN will be used as a 
platform so that other topics could be studied such as:

o 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.

o Optimizing 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 Buprenorphine with drug addiction counseling.
 
o 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.

o Effective therapies for treating marijuana abuse -- particularly in 
adolescent populations.

o Models for integrating new behavioral interventions into existing clinical 
practices.

In the area of HIV/AIDS research, examples are:
 
o 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 CTPs participating in the CTN must provide HIV risk reduction counseling 
and offer HIV testing. 
 
o Efficacy of drug abuse treatment on AIDS related outcomes, such as rate of 
progression to AIDS.  Studies could examine the effects of: 1) the early 
treatment of HIV, Hepatitis B and C and Sexually Transmitted Diseases, or 2) 
the prevention and early treatment of co-morbid medical and mental health 
conditions associated with HIV/AIDS infection. Such 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 platform for health service research and a much needed vehicle 
to recruit study subjects for such related topics as the genetic 
vulnerability to addiction, which would be funded under separate research 
grants.

In the area of genetics studies, examples are:

o Studies that better describe, disseminate, and predict the complex nature 
and course of drug abuse and addiction to offer more precise phenotypic 
indices for testing of hypothesized underlying genetic risk factors 
associated with drug abuse.

o Pharmacogenetics into ongoing medications trials for response to treatment 
and/or therapeutic outcome.  Examples could include accurate and 
comprehensive descriptions of phenotypes and associations with genotype to 
disease (phenotype-to-genotype approach), or selection of appropriate 
candidate gene variants to examine for association to a given drug response 
or outcome (genotype-to-phenotype approach)

In the area of health service research, an example is:

o Studies to describe 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.  

Although not all Nodes would be expected to have the capacity to conduct 
studies in HIV/AIDS, genetics and health services, all Nodes will be expected 
to collaborate in research focusing on such issues and to aid in recruitment 
of appropriate subjects.  Please reference the CTN policy on using the CTN as 
a research platform. http://www.nida.nih.gov/CTN/policies.html.

Nodes with expertise in these special areas will be given priority when 
making funding decisions.

MECHANISM OF SUPPORT 

This RFA will use NIH U10 award mechanism(s).  As an applicant you will be 
solely responsible for planning, directing, and executing the proposed 
project.  This RFA is a one-time solicitation.  The anticipated award date is 
August 31, 2005.  

The NIH (U10) is a cooperative agreement award mechanism. In the cooperative 
agreement mechanism, the Principal Investigator retains the primary 
responsibility and dominant role for planning, directing, and executing the 
proposed project, with NIH staff being substantially involved as a partner 
with the Principal Investigator, as described under the section "Cooperative 
Agreement Terms and Conditions of Award"  

FUNDS AVAILABLE 

It is expected that each Node will have an operating budget of up to $2.2 
million per year, comprised of grant awards of $1.25 million to pay for core 
support with additional funds available for implementation of protocols. 
There are also funds to support a separate contract which covers data 
management, data analysis, and portions of quality assurance monitoring, 
training and regulatory affairs.  NIDA expects to make up to eleven awards 
under this RFA for project periods of up to 5 years of support. It is 
anticipated that there will be subsequent RFAs to sustain or expand the CTN.  
It is projected that competing continuation applications will be invited upon 
expiration of the initial funding period of awards made under this and 
previous RFAs, subject to availability of funds. 

For new applicants, in general, no more than $700,000 in direct costs should 
be allocated to support first year operations. Therefore, the budgets for 
ensuing years (year two through year five) should be increased to reflect 
anticipated costs associated with maintaining the Node infrastructure and 
performing research projects.  

Because the role and function of a CTN Research Node is well established, it 
is expected that the size of individual awards for core support will be 
similar.  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 NIDA, awards pursuant to this RFA are contingent upon the 
availability of funds for this purpose.

ELIGIBLE INSTITUTIONS
 
You may submit (an) application(s) if your institution has any of the 
following characteristics: 
   
o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges,             
hospitals, and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic institutions/organizations
o Foreign institutions are not eligible to apply 
o Faith-based or community-based organizations

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS   

Any individual with the skills, knowledge, and resources necessary to carry 
out the proposed research is invited to work with their institution to 
develop an application for support.  Individuals from underrepresented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.
   
The Principal Investigators must commit to and be actively involved in the 
research and governance of the CTN at a minimum of 50 percent effort and 
document a substantial history of leadership in clinical trials research and 
an extensive research publication record.   

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 Principal Investigator must commit 
at least 50% effort to this project. 

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

Cooperative Agreement 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 Center for Clinical Trials Network (CCTN) and 
the Principal Investigators of the CTN Nodes. The NIDA CCTN will assist in 
coordinating 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. The awardee further agrees to accept close coordination 
and to cooperate fully with NIDA designated coordinating centers that will be 
responsible implementing approved protocols.  Specifically, awardees have 
primary responsibilities as described below. 

a. Steering Committee:

Awardees participate in The National Drug Abuse Treatment Clinical Trials 
Network (CTN) Steering Committee that serves as the governing body of the 
CTN.  The voting membership of the Steering Committee consists of the 
Principal Investigator and a CTP Director representative of each RRTC, and 
two representatives from NIDA, one of which is the NIDA CCTN Director. There 
are also two representatives from the Clinical Coordinating Center and the 
Data and Statistics Center. The Steering Committee reviews and approves the 
research agenda, formulates and monitors policies and procedures guiding the 
research activities, and oversees communications within the CTN as well as 
with the greater scientific community and the public. 

All major decisions are 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 undertaken within 
the CTN is determined by the Steering Committee based on input from the Nodes 
and subject to the approval of the Protocol Review Board and NIDA. Future 
research must be within and consistent with the scientific objectives of the 
RFA. 

The Steering Committee policies and standard operating procedures 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 has established CTN performance goals and monitors 
progress throughout the life of the CTN and its research projects.  Standard 
operating procedures and policies governing the CTN are available at 
http://www.nida.nih.gov/CTN/policies.html.  

b. Policies/Operating Procedures 

The Steering Committee 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, project initiation, conduct, 
and closure, data collection and management, 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:

o 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 operating center for a Node, has primary 
responsibility for 1) establishing an infrastructure for core functions, 2) 
generating a research agenda, 3) providing the Node with administration and 
operations support, and 4) building partnerships with the CTPs. 

o 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, with possibility for expansion 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, 5) collaborating with NIDA and other 
Nodes to develop, implement, and disseminate findings from CTN research 
projects 6)working with the CTN Clinical Coordinating Center and Data and 
Statistics Center. 

o Research Agenda/implementation - 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 concept, a 
protocol specific project team will be established to develop and implement 
the research project. It is expected that a Lead Investigator will come from 
the Node where the research concept and protocol originate. NIDA Staff may be 
designated as scientific and programmatic collaborators on the project team. 
The Lead Investigator will assume the leadership role for all aspects of that 
specific protocol and serve as the primary liaison to CTN-wide 
coordination/support centers as needed. 

a. Protocol Development: 

The Principal Investigator of a RRTC in collaboration with local CTPs, Co-
PIs, and other Network colleagues shall initiate the development of a 
clinical trial concept and once that concept is approved by the Steering 
Committee and NIDA, the Lead Investigator from that Node shall expeditiously 
draft a research protocol according to Steering Committee guidelines for 
protocol content and format. The Steering Committee will review and approve 
RRTC initiated protocols. Such review will include provisions for NIDA 
scientific review and comment, including review by an independent 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. 

The Principal Investigators of RRTCs agree to cooperate with NIDA’s 
contracted Data and Statistical Center with regard to CTN-wide standards for 
collection and analysis of data generated under the CTN, and enabling the 
Data and Statistics Center to provide timely, accurate, and complete data for 
purposes of monitoring the safety and progress of research projects conducted 
within the CTN, as well as final study data according to schedules developed 
and approved by the Steering Committee for individual research projects 
conducted through the CTN. 

b. Data Rights: 

The NIH expects investigators supported by NIH funding to make their research 
data available to the scientific community for subsequent analysis based on a 
data sharing plan approved as part of the award; see the NIH data sharing 
policy website at http://grants.nih.gov/grants/policy/data_sharing 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. At the conclusion of each protocol, 
the Lead Investigator will be required to direct the data coordinating center 
to produce a public use file of all related study data.  The format and 
documentation of the data should be complete enough to replicate the studies 
outcomes and ensure its broader utilization by the drug abuse treatment 
community while maintaining subject confidentiality. 

c. Quality Assurance and Monitoring:

All clinical trials are subject to quality control and monitoring as stated 
by CTN Quality Assurance (QA) and Monitoring policies and procedures. The 
Lead Investigator of each trial is primarily responsible for design of study 
QA monitoring plan according to the CTN policies and procedures. In addition, 
NIDA or its representative, the Clinical Coordinating Center, will provide 
periodic oversight and Quality Assurance monitoring of all clinical trial 
sites following the Good Clinical Practice (GCP) standards.  Awardee agrees 
to permit on site monitoring for all of its community treatment provider 
sites.  

For medication trials, NIDA, when necessary, will be the holder of the 
Investigational New Drug application (IND). When there is an IND, NIDA will 
be primarily responsible for study control and monitoring as defined by FDA 
rules and regulations. When NIDA holds the IND, the RRTCs will be subject to 
review by NIDA to ensure adherence to GCP. The Awardee agrees to provide 
material and documentation needed to assure GCP compliance.  

d. Training:

A Training Tracking System has been developed by the CTN to track the 
required training of staff throughout the network. The system tracks two 
components, staff training requirements and training attendance. The purpose 
of the system is to identify the training delivered and document that the 
training requirements have been satisfied.  Reports are available to the CTN 
community via its secured web-based document repository (Livelink).  Awardees 
agree to enter training information into this CTN wide system. 

e. 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, and 
other research projects, 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 are not limited to, 
Title 21 CFR Parts 11, 50, 56, 312, and Title 45 CFR 46. The RRTC must be 
able to demonstrate that each institution and CTP has a current, approved, 
Institutional Assurance of Protection for Human Subjects on file with the 
Department of Health and Human Services Office for Human Research 
Protections; that each protocol and informed consent is approved by the 
recognized Institutional Review Board (IRB) prior to the enrollment of 
subjects in any study; and that each subject (or legal representative) has 
given necessary 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. 
 
f. Unexpected Adverse Experience Reporting: 

The Principal Investigator of the RRTC agrees to implement and adhere to an 
adverse event tracking system operated by NIDA and adopted by the Steering 
Committee.

g. 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: 

CTN Node Operations Reports:  Awardees are required and agree to provide 
quarterly reports of program activities to NIDA by the 10th day of the month 
following the end of programmatic quarters (90 days from the date of award).  
These reports include: 1) a quarterly progress report of the activities of 
the Node within the reporting period and 2) quarterly financial reports 
showing a breakdown of the costs incurred for both the RRTC and CTPs for the 
reporting period. The quarterly financial report shall include a total of all 
costs spent in previous quarters for that year as well as the current 
reporting period.  This report is in addition to the yearly Federal Status 
Report (FSR) required by NIH.  The CCTN/NIDA will define a recommended format 
and specify minimum content for these Program Operations Reports. 

CTN Research Project Reports:  Awardees are required and agree to provide 
periodic reports of the research projects undertaken in the CTN. At minimum 
the Lead Investigator must provide timely information on the tasks, schedule, 
and costs associated with the development and implementation of a CTN 
research project.  Enrollment information in a format and according to a 
schedule defined by NIDA and the Steering Committee are required for each CTN 
clinical research project. 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.  

Final Study Report: Lead Investigators are required to provide the Director, 
CCTN and the Steering Committee with a Final Study Report within 120 days of 
data lock upon completion of the protocol. The Final Study Report is a brief 
accounting of the history, participants, and milestones in the completion of 
the trial. The content and format are approved by the Steering Committee. 

h. Publication of Data: 

Prompt and timely presentation and publication in the scientific literature 
of findings resulting from research undertaken in the CTN is required. It is 
expected that the Lead Investigator will have an initial outcome paper 
completed and submitted to an appropriate peer-reviewed scientific journal 
within 180 days of data lock for the protocol. 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.  

i. Progress Review  

The CTN Steering Committee has established and will continue to elaborate 
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 have been defined to permit NIDA 
and the CTN Steering Committee a means to assess progress of the Node 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.

j. National Meetings: 

The Steering Committee may meet up to four (4) times each year. The Principal 
Investigator agrees to provide adequate support for participation in CTN 
meetings as required by the Steering Committee and its various operating sub-
committees. The Principal Investigator agrees to support participation by CTP 
personnel as required by CTN projects.

k. Conflict of Interest: 

Awardees are required to comply with 42 CRF part 50, subpart F 
“Responsibility of Applicants for promoting Objectivity in Research for Which 
PHS Funding is Sought.”  In addition, the CTN Steering Committee has 
developed policies on Conflict of Interest and monitors compliance to that 
policy. The Conflict of Interest Policy addresses issues that may arise 
through financial ties between RRTC and CTP participants and the private 
sectors. Awardees will abide by the CTN Conflict of Interest Policy and 
ensure staff identified in the policy provide disclosure to the CCTN as 
required.  This policy can be found at: 
http://grants.nih.gov/grants/policy/coi/index.htm or
http://www.nida.nih.gov/CTN/policies.html

l. Protocol Closure: 

Throughout the term of the cooperative agreement NIDA may request that a 
research project be terminated 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 project 
closure, except that funds may remain available for patients already enrolled 
in the study.

3. RRTC and CTPs: 

a. The RRTC agrees to negotiate and establish subcontracts with at least five 
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; 
-- Screen and recruit adequate numbers of patients required to meet the 
expectation of specific protocols. This frequently requires recruiting one 
patient per week.  
-- 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 access to HIV testing; 
-- Provide HCV education and referral for testing and treatment;
-- Maintain patient records and other source documents required for each 
protocol; 
--Collect clinical and laboratory data, including biological specimens when 
indicated; 
-- Cooperate with quality assurance activities of the CTN and adhere to 
guidelines set by the RRTC, the Steering Committee, and NIDA; 
-- Cooperate with NIDA’s Clinical Coordinating Center and Data and Statistics 
Center
-- Participate in the development of research concepts and protocols for 
trials to be conducted 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 appropriate use of investigational drugs; 
compliance with regulations for FDA, IRB approval or informed consent 
(compliance with 45 CFR 46); misconduct in science inquires; compliance with 
protocol specifications; quality assurance and accuracy of data recording; 
and completeness of reporting of adverse drug reactions.

CTPs are not expected to participate in every CTN research project, but must 
adhere to the above terms when they choose to participate in a CTN research 
project. 

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

NIDA staff do have and 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 in these terms and conditions.

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.

NIDA maintains a Logistic Support Center (LSC) through contract. These 
central resources support certain administrative coordinating functions of 
the CTN. These include: 1) Logistical support for meetings of the Network, 
e.g., CTN Steering Committee, subcommittees, workgroups and other Boards (the 
Advisory Board, the DSMB, etc.), 2) Reproduction and distribution of research 
and educational materials, including treatment protocols, training manuals, 
and instrumentation, 3) Development, reproduction, and distribution of 
materials publicizing the activities of the CTN. 

a. NIDA’s Scientific Role 

NIDA Collaborating Scientists (CSs) with expertise in behavioral therapies, 
medications development, and practice research may 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. A 
collaborating scientist is assigned such responsibility only with the 
approval of the Director, CCTN. 

The NIDA CCTN 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.

The following Boards will have approval authorities as indicated:

NIDA Protocol Review Board: An expert board authorized by the NIDA Director 
that will review the final draft of the protocol submitted by the Lead 
Investigator and the Protocol Development Team 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 review 
study plans and 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 the effectiveness of 
interventions under investigation and whether a trial will continue. One or 
more NIDA staff will serve as non-voting members on the DSMB. 

b. NIDA’s Role in Protocol Review and Approval

In order for a CTN research project to be initiated, the study proposal must 
be mutually approved by the CTN Steering Committee and NIDA. Once notified 
that a clinical 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. The Lead Investigator for the protocol is required to provide 
the CCTN with a cost projection and rationale for the resource requirements 
for protocol implementation.  

Prior to protocol approval as defined above, NIDA will provide no trial 
materials or permit expenditure of CTN funds to implement the research 
project 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 Approval to Enroll Study Participants

CTN research projects may proceed upon the Lead Investigator receiving 
approval from the NIDA CCTN Director that enrollment may begin. The Lead 
Investigator is responsible for providing all necessary documentation of the 
readiness of each participating site to initiate participant enrollment. Such 
documentation will include 1) evidence of IRB approval for each clinical 
site, 2) evidence of data system readiness based on the successful test and 
certification by NIDA’s Data and Statistics Center, 3) evidence that all 
participating project personnel both at the CTP and the RRTC have received 
the training needed to conduct the research according to the protocol and 
that this information has been documented in the CTN Training Tracking Data 
Base and 4) evidence that the protocol quality assurance plans are in place 
to monitor the research project at participating clinical sites.  

d. NIDA’s Role During Protocol Conduct

For ongoing research projects NIDA personnel and its contractors will monitor 
the safety of study participants through review of incremental case report 
form.  For all clinical trials, NIDA will assign a Medical Officer who will 
be responsible for the review and disposition of adverse events that may 
arise in the course of a study.  NIDA will prepare periodic reports profiling 
the conduct of the study including the safety of study participants for 
review by the CTN Data and Safety Monitoring Board (DSMB).  

e. NIDA’s Role in Protocol Closure

The NIDA CCTN 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 or study performance issues.  
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.

f. NIDA Access to Data

The NIDA CCTN Director, and/or designated 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. 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.

g. 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 Steering Committee and NIDA.

h. NIDA Review of CTN Compliance with Federally Mandated Regulatory 
Requirements

The NIDA CCTN 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 DHHS Office for Human Research 
Protections regulations for the protection of human volunteers in clinical 
research studies.

i. Review of Performance

The NIDA CCTN Director will review the performance of the CTN as a whole and 
of individual RRTCs. at least once every two years.  Such reviews will 
include periodic reviews of the RRTC and its CTP sites for compliance with 
clinical and regulatory guidelines and success in achieving the performance 
standards established by the CTN Steering Committee. The review will be based 
on information provided in periodic progress reports defined elsewhere in 
these Terms and Conditions, and evaluations of site performance conducted by 
the CCTN staff. Insufficient patient accrual, substandard data 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. 

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity to 
answer questions from potential applicants.  Inquiries may fall into three 
areas:  scientific/research, peer review, and financial or grants management 
issues:

o Direct your questions about scientific/research issues to:

Betty Tai, Ph.D.
Center for the Clinical Trials Network  
National Institute on Drug Abuse, NIH, DHHS
6001 Executive Boulevard, Room 3103, MSC 9557
Bethesda, MD 20892-9557
Telephone: (301) 443-6697
FAX: (301) 443-2317
Email: btai@nida.nih.gov
 
o Direct your questions about peer review issues to:

Teresa Levitin, Ph.D.
Office of Extramural Affairs
National Institute on Drug Abuse, NIH, DHHS
6101 Executive Boulevard, Suite 234, MSC 8401
Bethesda, Maryland  20892-8401
Telephone:  (301) 443-2755
FAX:  (301) 443-0538
Email:  tlevitin@mail.nih.gov

o Direct your questions about financial or grants management matters to:

Dr. Gary Fleming
Chief, Grants Management Branch
National Institute on Drug Abuse, NIH, DHHS
6101 Executive Boulevard, Room 270, MSC 8403
Bethesda, Maryland  20892-8403
Rockville, MD 20852  (for express/courier service)
Telephone:  301-443-6710
Fax:  301-594-6849
E-mail:  GF6S@NIH.GOV

LETTER OF INTENT
 
Prospective applicants are asked to submit a letter of intent that includes 
the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 

Although a letter of intent is not required, is not binding, and does not 
enter into the review of a subsequent application, the information that it 
contains allows IC staff to estimate the potential review workload and plan 
the review.
 
The letter of intent is to be sent by the date listed at the beginning of 
this document.  The letter of intent should be sent to:

DA05-001
Director
Office of Extramural Affairs
National Institute on Drug Abuse, NIH, DHHS
6101 Executive Boulevard, Suite 220, MSC 8401
Bethesda, Maryland  20892-8401
Telephone:  (301) 443-2755
FAX:  (301) 443-0538
Email:  tlevitin@mail.nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001). Applications must have a DUN and 
Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the 
Universal Identifier when applying for Federal grants or cooperative 
agreements. The DUNS number can be obtained by calling (866) 705-5711 or 
through the web site at http://www.dunandbradstreet.com/. The DUNS number 
should be entered on line 11 of the face page of the PHS 398 form. The PHS 
398 document is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 435-0714, 
Email: GrantsInfo@nih.gov.
 
USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) 
application form must be affixed to the bottom of the face page of the 
application.  Type the RFA number on the label.  Failure to use this label 
could result in delayed processing of the application such that it may not 
reach the review committee in time for review.  In addition, the RFA title 
and number must be typed on line 2 of the face page of the application form 
and the YES box must be marked. The RFA label is also available at: 
http://grants.nih.gov/grants/funding/phs398/labels.pdf.
 
SENDING AN APPLICATION TO THE NIH: 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, DHHS
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)
 
At the time of submission, two additional copies of the application and all 
copies of the appendix material must be sent to:

DA05-001
Director
Office of Extramural Affairs
National Institute on Drug Abuse, NIH, DHHS
6101 Executive Boulevard, Suite 220, MSC 8401
Bethesda, Maryland  20892-8401
Telephone:  (301) 443-2755
FAX:  (301) 443-0538
Email:  tlevitin@mail.nih.gov

APPLICATION PROCESSING: Applications must be received on or before the 
application receipt date listed in the heading of this RFA.  If an 
application is received after that date, it will be returned to the applicant 
without review. 

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignment within 8 weeks.
 
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.  
However, when a previously unfunded application, originally submitted as an 
investigator-initiated application, is to be submitted in response to an RFA, 
it is to be prepared as a NEW application.  That is, the application for the 
RFA must not include an Introduction describing the changes and improvements 
made, and the text must not be marked to indicate the changes from the 
previous unfunded version of the application.  

SUPPLEMENTARY 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 addresses 
the fundamental goals and collaborative nature of the CTN. 

The use of tables, diagrams, and organizational and flow charts is strongly 
encouraged.

APPLICATION PACKAGE

The application should conform to the general instructions and requirements 
of the PHS 398 (rev. 5/2001) with the exceptions noted below.   

Sections a-d need not be organized according to Specific Aims, Background and 
Significance, etc. as stated in the PHS 398 application kit.  It is suggested 
that sections a-d be replaced with the following sections.  Note, also the 
page limits described in a subsequent section of this announcement.

SPECIFIC REQUIREMENTS FOR COMPETING CONTINUATION APPLICATIONS

Progress Report Section

An application from a currently funded Node will be a competing continuation.  
It is recognized that each competing continuation application will present 
both unique features and activities carried out in common with other CTN 
Nodes.  Applications are expected to provide evidence of their contributions 
to shared CTN activities as well as to provide evidence of their unique 
strengths and accomplishments.  A competing continuation application must 
include a progress report which at minimum consists of: 

1.   Evidence of efficient administrative structure/personnel in managing 
multi-site trials, ability to participate in multi-site trials;
2.   A summary of research activities/accomplishments during the prior funding 
period, including a clear presentation of annual accrual to all 
participating protocols, and the gender/ethnic minority composition of 
recruited study populations, from affiliated CTPs and how well accrual 
met CTN accrual goals, and scientific publications and presentations;
3.   Status of any concepts developed by the applicants, i.e.,  concepts 
developed and submitted by the Node and any concepts accepted for 
development CTN-wide;
4.   Progress in developing and implementing research protocols, including the 
details of the process and organizational structure for protocol 
development and implementation, efficient and extensive Node training 
activities to ensure efficiency in performing protocols, QA to ensure 
adherence to protocol requirements and patient well being and safety, 
quality data management, etc.;
5.   Evidence of ability to engage community treatment programs in bi-
directional communications to bridge the research to practice gap;
6.   Evidence of participation and leadership in CTN research and 
administrative activities;
7.   Summary of unique contributions of the Node to CTN-wide activities in the 
prior funding period.

REQUIREMENTS FOR ALL APPLICATIONS: The following sections are to be used by 
all applicants, both for new and competing continuation applications.

1.   Understanding of and Ability to Contribute to the Mission of the CTN: 

This section should consist of a few pages to establish the applicant’s 
understanding of the CTN and describe how the proposed Node contributes to 
the CTN goals.

2.   Administrative and Management Plans: 
 
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.  Evidence of 
participation in multi-site clinical trials is desirable.

It is important to demonstrate the Principal Investigator’s ability to 
contribute to the scientific agenda and commit a minimum of 50 percent of 
time 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 communications encompassing all of the Node's CTPs 
should be specified. Diagrams and descriptions of proposed intra-Node 
committee structures should be given. 

Each applicant must demonstrate the ability to train and maintain the 
proficiency of RRTC and CTP personnel to successfully manage treatment and 
clinical trials research.  

3.  Research and Clinical Infrastructures:

The plans should document the availability of appropriate expertise within 
the RRTC to design, implement, and analyze the results of proposed trials. 

The plans should describe the infrastructure for core functions, which 
include but are not limited to managing the participation of CTPs in CTN 
activities, staffing technical personnel for protocol design, development and 
implementation, and providing resources for and coordination of intra-Node 
activities. The plans should also elaborate on the infrastructure 
capabilities in research administration, project management, protocol design 
and development, quality assurance and regulatory affairs. 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. 

Applicants must demonstrate access to diverse racial and ethnic populations 
through the aggregate of their proposed community treatment providers. 

4.  Collaborations between the RRTC and CTPs:

The application should describe the relationships between the CTPs and RRTC.  
It should provide detailed descriptions of CTPs that will participate, with 
detailed descriptions of each CTP’s characteristics, including patient 
population characteristics, patient throughput, types of treatment currently 
delivered, and staff number, characteristics, and structure. See outline that 
follows this paragraph. Each CTP’s description is limited to two pages of 
text. It will be critical for the Node to recruit and retain sufficient CTPs 
to participate in multiple simultaneous trials.  The possibility of expanding 
the number of CTPs should be addressed.  The appendix should contain letters 
of agreement from CTP directors and tables, as needed, to describe the CTPs. 

For each Community Treatment Program (CTP)

1.   Name of Organization
2.   Address
3.   Telephone
4.   Fax Number
5.   Director/Contact (person who will work with the CTN, serve on 
committees, etc.)
6.   E-Mail Address of Director/Contact

Characteristics of each CTP to include:
1.   Number of clinical sites in organization
2.   Static capacity -- at any one time, what is the CTP’s total patient 
census?
3.   Annual patient admissions by treatment modality
4.   Rural or urban -- is the CTP located in a rural or urban community?
5.   Clinic patient characteristics: 
o  Percent Black, African-American
o  Percent Hispanic, Latino
o  Percent White, Caucasian
o  Percent American Indian or Alaskan Native
o  Percent Asian or Pacific Islander
6.   Gender breakdown of patients -- percent male, percent female
7.   Age breakdown of patients -- percent adolescent (under 21), percent 
over 65 if known (Medicare)
8.   Does this agency serve pregnant women, families with children, etc?  
Percent of clients who fall into these categories.
9.   What kinds of HIV/HCV services are currently offered?  1) Education and 
prevention; 2) testing and counseling; and/or 3) treatment for HIV/HCV
10.   Classify the CTP as either (“Drug-Free”) Psychosocial, Methadone (and 
Buprenorphine), or both 
11.   Does the CTP offer behavioral treatment?  If so, what types of 
treatment are offered?  Is treatment provided in individual or group 
sessions, or both?
12.   Categorize setting as:  1) Outpatient; 2) Residential; 3) Post-
residential; 4) IOP (Intensive Outpatient Treatment); 5) TC 
(Therapeutic Community) -- treatment beyond the standard 6-8 week 
program; 6) Day care -- all day 8-5, 5 days per week; or 7) Half-way 
House
13.   Does the CTP treat patients who are classified as co-morbid? (Dually 
diagnosed)
14.   Are faith-based treatment services part of the program?  Please 
describe.
15.   Primary source of program funding: Patient Fees, Public Insurance, 
Public grant or contracts, Private Insurance
16.   Any other pertinent characteristics of the CTPs proposed in your grant

An organizational chart to describe the functional structure of RRTC and CTP 
personnel in the design and implementation of a variety of clinical research 
projects should be provided in the body of the application (i.e., within the 
45 pages). An organizational chart and a description of the RRTC operation 
should describe the relationship between the research and administrative 
functional units within the Node. Evidence of current or previous successful 
collaborations with the community treatment programs would be desirable. 

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 research concept origination, protocol design, research project 
implementation, and administrative support services. 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. 

5.  Research Concept:

Applicants should not propose a detailed research protocol, but rather should 
provide a specific example of a research concept and an abbreviated plan that 
could be undertaken and is consistent with the RFA to take advantage of the 
unique capabilities of the CTN, including collaboration across Nodes.  The 
concept should present a discussion of the types of research questions that 
could be addressed, research methods that might be used, and patient 
populations that might be employed.  Particular emphasis should be placed on 
how the applicant proposes to ensure that the RRTC and the CTPs of the Node 
will work collaboratively at all levels, and that the Node will be able to 
work collaboratively with other Nodes and NIDA in multi-site clinical trials.  
It should be understood that the concept example may not necessarily be 
implemented in the CTN.

The research plans for the proposed concept should include descriptions of 
research study design, interventions, outcome measures, and statistical 
considerations; access to appropriate patients; procedures for data 
management, a training plan, quality control and follow-up; procedures for 
monitoring and reporting adverse events; and information on human subjects’ 
protections.  Finally, there should be a cost estimate displayed as a 
protocol budget. This concept must include details according to the SOPs 
detailed in the following web site. http://www.nida.nih.gov/CTN/policies.html

6. Human Subjects Research (research plan section e): 

The application should describe plans for human subject protections, data and 
safety monitoring as well as gender and minority information about patient 
populations for the CTN Node as a whole.

7. Other:

There should be information on literature cited, contractual arrangements, 
etc. as specified in the PHS 398. 

Budget

The budget and accompanying justification are not part of the 45 page limit.  
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.  

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 costs, logistic support, travel, 
etc.); 2) CTP support to conduct clinical trials; 3) Lead Node 
responsibilities for the scientific leadership of research projects.  As 
noted elsewhere in this RFA, funds for Node travel should be included to 
provide for participation in CTN related meetings.

Page Limits

To summarize the guidance above, the total length of the Research Plan, 
including the CTP descriptions and research concept and administrative and 
management plan should not exceed 45 pages. Descriptions of CTPs should not 
exceed 2 pages per program. Descriptions of research concept should not 
exceed 10 pages.  Literature Cited and Consortium/Contractual Arrangements 
sections should be provided following the 45 pages and in total should not 
exceed 15 pages. 

PEER REVIEW PROCESS  
 
Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by NIDA. Incomplete and/or nonresponsive applications will not 
be reviewed.  

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 in accordance with the review criteria stated below.  As 
part of the initial merit review, all applications will:

o Undergo a process in which only those applications deemed to have the 
highest scientific merit, generally the top half of the applications under 
review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by the National Advisory Council on Drug 
Abuse.

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to evaluate the application in 
order to judge the likelihood that the proposed research will have a 
substantial impact on the pursuit of these goals. The scientific review group 
will address and consider each of the following criteria in assigning the 
application’s overall score, weighting them as appropriate for each 
application. 

o Significance 
o Approach 
o Innovation
o Investigator
o Environment
  
The application does not need to be strong in all categories to be judged 
likely to have major scientific impact and thus deserve a high priority 
score.  For example, an investigator may propose to carry out important work 
that by its nature is not innovative but is essential to move a field 
forward.
   
1.  UNDERSTANDING THE CTN

o How well does the proposed Node (i.e., the applicant RRTC and its 
affiliated community treatment programs) demonstrate an understanding of the 
scientific agenda of the Clinical Trials Network (CTN)?  
o To what extent would the proposed Node likely contribute or continue to 
contribute to the goals and enhance the capability of a nationwide CTN? 

2.  ADMINISTRATIVE AND MANAGEMENT PLANS   

o How strong are the plans for overall Node management and operations, 
including the structure and mechanisms for effective intra-Node communication 
and collaboration and involving appropriate personnel in the design and 
implementation of protocols?
o How strong are the applicant's previous experience and plans for training 
RRTC and community treatment personnel, including therapists and research 
associates, in implementing multi-site clinical trials?
o How strong are the plans for effective interaction and coordination with 
other Nodes and NIDA? 

3.  RESEARCH AND CLINICAL INFRASTRUCTURE    

o Is there sufficient evidence that the proposed Principal Investigator (PI) 
will be (or has devoted) adequate time to carry out the work of the CTN?  
(Must be a minimum of 50%)
o How strong are the previous research experience and other qualifications of 
the PI and other key staff in design, administration, and management of 
multi-site clinical trials, including quality control, quality assurance, and 
data management procedures?  
o How strong are the qualifications of key personnel and scientific staff in 
the areas of the proposed research concept and in the more general skills 
needed to develop, conduct, and analyze clinical trials? 
o How good are the available resources and proposed personnel for 
administering Node participation in clinical trials, including adequacy of 
procedures to collect, monitor, and analyze the data and assure the safety of 
patients/participants?  
o How strong is the evidence of infrastructure capabilities in project 
management, protocol development, and knowledge of regulatory affairs?
o How strong is the Node’s capacity to include appropriate representation of 
gender, minorities and their subgroups, and subjects with a range of ages 
appropriate for the scientific goals of the research?  
o How strong is the Node’s capacity to conduct research on HIV/AIDS and 
substance abuse?

4.  COLLABORATION BETWEEN RRTC AND CTPs
 
o Is there a record of previous RRTC-CTP collaboration, including  orienting 
community personnel to protocol requirements, organizing scientific and 
educational meetings for those participating in the clinical trials, and 
participating in inter-group clinical trials.?  
o What is the quality of plans for involving CTPs in the research and 
organizational activities of the CTN? 
o How well developed are the RRTC's criteria for selecting CTPs with diverse 
geographic and population representation (as balanced by constraints of 
reasonable management)?
o How good are the quality of the proposed CTPs and the experience of their 
program directors?  
o To what extent do the proposed CTPs vary programmatically?  To what extent 
are they able to accrue a demographically diverse patient population?
o How feasible are CTP plans for patient enrollment and retention?  How well 
do the CTPs demonstrate their ability to accrue patients at an adequate rate 
to support multi-site clinical trials? 

5.  RESEARCH PLANS
   
o How well does the proposed research concept demonstrate knowledge of state-
of-the-art research designs, methodologies, and operations?
o Does the plan have the potential to produce a major improvement in the 
quality and effectiveness of drug treatment? 

6. PROGRESS (For competing continuation applications):

Evaluate the adequacy of progress in:
o developing and implementing protocols
o subject accrual and retention
o data management 
o evaluation/monitoring of Node activities 
o publication/presentation of research findings, and other dissemination of 
findings 
o level of participation and leadership in CTN-wide protocols 
o level of participation and leadership in CTN-wide committees
o assess unique strengths and limitations this node brings to the CTN as a    
whole

7.  OTHER

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:
o The adequacy of plans to include both genders, minorities and their 
subgroups, and children as appropriate for the scientific goals of the 
research. 
o Plans for the recruitment and retention of subjects will also be evaluated.
o The adequacy of the proposed protection for humans, animals or the 
environment, to the extent they may be adversely affected by the project 
proposed in the application.
o The plans for data and safety monitoring will be assessed. 

8.  BUDGET

o The reasonableness of the proposed budget and duration in relation to the 
proposed research.
o How appropriate are the budget estimates for infrastructure to enable the 
RRTC to provide core functions for the Node (e.g., personnel, facilities, 
equipment, supplies,  logistic support, travel)?
o How appropriate are budget estimates for CTP support to conduct the 
clinical trials?
o How adequate are plans for budgetary control and oversight?

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following 
items will be considered in the determination of scientific merit and the 
priority score:

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human 
subjects and protections from research risk relating to their participation 
in the proposed research will be assessed. (See criteria included in the 
section on Federal Citations, below).
 
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of 
plans to include subjects from both genders, all racial and ethnic groups 
(and subgroups), and children as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects will also be 
evaluated. (See Inclusion Criteria in the sections on Federal Citations, 
below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to 
be used in the project, the five items described under Section f of the PHS 
398 research grant application instructions (rev. 5/2001) will be assessed.  

ADDITIONAL REVIEW CONSIDERATIONS

Sharing Research Data:

Applicants requesting more than $500,000 in direct costs in any year of the 
proposed research must include a data sharing plan in their application. The 
reasonableness of the data sharing plan or the rationale for not sharing 
research data will be assessed by the reviewers. However, reviewers will not 
factor the proposed data sharing plan into the determination of scientific 
merit or priority score. 

BUDGET:  The reasonableness of the proposed budget and the requested period 
of support in relation to the proposed research.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:  September 14, 2004
Application Receipt Date:  October 14, 2004
Peer Review Date:  December 2004-January 2005
Council Review:   May 2005   
Earliest Anticipated Start Date:  July 2005

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities, including program balance, ability to use the CTN 
as a platform for training clinical researchers and as a platform for other 
research (e.g., health services, genetics, and HIV/AIDS), and geographic 
representation.
 
REQUIRED FEDERAL CITATIONS 

ANIMAL WELFARE PROTECTION:  Recipients of PHS support for activities 
involving live, vertebrate animals must comply with PHS Policy on Humane Care 
and Use of Laboratory Animals 
(http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf), as 
mandated by the Health Research Extension Act of 1985 
(http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA 
Animal Welfare Regulations 
(http://www.nal.usda.gov/awic/legislat/usdaleg1.htm), as applicable.

HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated with 
reference to the risks to the subjects, the adequacy of protection against 
these risks, the potential benefits of the research to the subjects and 
others, and the importance of the knowledge gained or to be gained.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm 

DATA AND SAFETY MONITORING PLAN:  Data and safety monitoring is required for 
all types of clinical trials, including physiologic, toxicity, and dose-
finding studies (phase I); efficacy studies (phase II); efficacy, 
effectiveness and comparative trials (phase III).  The establishment of data 
and safety monitoring boards (DSMBs) is required for multi-site clinical 
trials involving interventions that entail potential risk to the 
participants. (NIH Policy for Data and Safety Monitoring, NIH Guide for 
Grants and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

SHARING RESEARCH DATA:  Investigators submitting an NIH application seeking 
$500,000 or more in direct costs in any single year are expected to include a 
plan for data sharing or state why this is not possible. 
http://grants.nih.gov/grants/policy/data_sharing  Investigators should seek 
guidance from their institutions, on issues related to institutional 
policies, local IRB rules, as well as local, state and Federal laws and 
regulations, including the Privacy Rule. Reviewers will consider the data 
sharing plan but will not factor the plan into the determination of the 
scientific merit or the priority score.

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: 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 clinical research projects unless a 
clear and compelling justification is provided indicating 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 clinical research should read the "NIH Guidelines 
for Inclusion of Women and Minorities as Subjects in Clinical Research - 
Amended, October, 2001," published in the NIH Guide for Grants and Contracts 
on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.   
The amended policy incorporates: the use of an NIH definition of clinical 
research; updated racial and ethnic categories in compliance with the new OMB 
standards; clarification of language governing NIH-defined Phase III clinical 
trials consistent with the new PHS Form 398; and updated roles and 
responsibilities of NIH staff and the extramural community.  The policy 
continues to require for all NIH-defined Phase III clinical trials that: a) 
all applications or proposals and/or protocols must provide a description of 
plans to conduct analyses, as appropriate, to address differences by 
sex/gender and/or racial/ethnic groups, including subgroups if applicable; and 
b) investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:  
The NIH maintains a policy 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. 

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 is available at 
http://grants.nih.gov/grants/funding/children/children.htm

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH 
policy requires education on the protection of human subject participants for 
all investigators submitting NIH proposals for research involving human 
subjects.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research 
on hESCs can be found at http://stemcells.nih.gov/index.asp and at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  Only 
research using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).   
It is the responsibility of the applicant to provide, in the project 
description and elsewhere in the application as appropriate, the official NIH 
identifier(s) for the hESC line(s)to be used in the proposed research.  
Applications that do not provide this information will be returned without 
review. 

HIV/AIDS COUNSELING AND TESTING POLICY FOR THE NATIONAL INSTITUTE ON DRUG 
ABUSE:  Researchers funded by NIDA who are conducting research in community 
outreach settings, clinical, hospital settings, or clinical laboratories and 
have ongoing contact with clients at risk for HIV infection, are strongly 
encouraged to provide HIV risk reduction education and counseling.  HIV 
counseling should include offering HIV testing available on-site or by 
referral to other HIV testing service for persons at risk for HIV infection 
including injecting drug users, crack cocaine users, and sexually active drug 
users and their sexual partners.  For more information see 
http://grants.nih.gov/grants/guide/notice-files/NOT-DA-01-001.html.

NATIONAL ADVISORY COUNCIL ON DRUG ABUSE RECOMMENDED GUIDELINES FOR THE 
ADMINISTRATION OF DRUGS TO HUMAN SUBJECTS:  The National Advisory Council on 
Drug Abuse recognizes the importance of research involving the administration 
of drugs to human subjects and has developed guidelines relevant to such 
research.   Potential applicants are encouraged to obtain and review these 
recommendations of Council before submitting an application that will 
administer compounds to human subjects.  The guidelines are available on 
NIDA's Home Page at http://www.nida.nih.gov under the Funding, or may be obtained by 
calling (301) 443-2755.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The 
Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) 
cited publicly and officially by a Federal agency in support of an action 
that has the force and effect of law (i.e., a regulation) may be accessed 
through FOIA.  It is important for applicants to understand the basic scope 
of this amendment.  NIH has provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:  The 
Department of Health and Human Services (DHHS) issued final modification to 
the “Standards for Privacy of Individually Identifiable Health Information”, 
the “Privacy Rule,” on August 14, 2002.  The Privacy Rule is a federal 
regulation under the Health Insurance Portability and Accountability Act 
(HIPAA) of 1996 that governs the protection of individually identifiable 
health information, and is administered and enforced by the DHHS Office for 
Civil Rights (OCR).  

Decisions about applicability and implementation of the Privacy Rule reside 
with the researcher and his/her institution. The OCR website 
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including 
a complete Regulation Text and a set of decision tools on “Am I a covered 
entity?”  Information on the impact of the HIPAA Privacy Rule on NIH 
processes involving the review, funding, and progress monitoring of grants, 
cooperative agreements, and research contracts can be found at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals 
for NIH funding must be self-contained within specified page limitations. 
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) 
should not be used to provide information necessary to the review because 
reviewers are under no obligation to view the Internet sites.   Furthermore, 
we caution reviewers that their anonymity may be compromised when they 
directly access an Internet site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of "Healthy 
People 2010," a PHS-led national activity for setting priority areas. This 
RFA is related to one or more of the priority areas. Potential applicants may 
obtain a copy of "Healthy People 2010" at http://www.healthypeople.gov/.

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems Agency review.  Awards are made under the authorization of Sections 
301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) 
and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92). All 
awards are subject to the terms and conditions, cost principles, and other 
considerations described in the NIH Grants Policy Statement.  The NIH Grants 
Policy Statement can be found at 
http://grants.nih.gov/grants/policy/policy.htm.  

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the use of all tobacco products.  In addition, 
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in 
certain facilities (or in some cases, any portion of a facility) in which 
regular or routine education, library, day care, health care, or early 
childhood development services are provided to children.  This is consistent 
with the PHS mission to protect and advance the physical and mental health of 
the American people.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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


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