Part I Overview Information

Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH) (http://www.nih.gov)

Components of Participating Organizations
National Institutes on Drug Abuse (NIDA) (http://www.nida.nih.gov)

Title: Announcement of a Limited Competition of THE NATIONAL DRUG ABUSE TREATMENT CLINICAL TRIALS NETWORK (U10)

Announcement Type
This is a reissue of RFA-DA-05-001 which was previously released July 07, 2004.

Update: The following update relating to this announcement has been issued:

• June 1, 2009 - This RFA has been reissued as (RFA-DA-10-009).

• This Request for Applications (RFA) from the National Institute on Drug Abuse (NIDA) announces a limited competition for competitive cooperative agreement renewal applications from established clinical investigators to participate in the National Drug Abuse Treatment Clinical Trials Network (CTN). The competition is restricted to only those institutions that currently house an existing, active Node in the CTN. As a nation-wide partnership among drug abuse treatment providers, researchers, and NIDA staff, the mission of the CTN is to improve the quality of drug abuse treatment throughout the country using science as the vehicle. The CTN provides an enterprise in which community-based service providers, treatment researchers, and NIDA cooperatively develop, validate, refine, and deliver new treatment options to patients in community-level clinical practice.
• NIDA expects to award up to a total of $7.5 million per year.
• NIDA anticipates awarding up to 3-6 awards under this RFA.
• This RFA will use the National Institutes of Health (NIH) cooperative agreement (U10) award mechanism.
• Eligible organizations include only those organizations and institutions that that currently house an existing, active Node in the CTN. Foreign institutions are not eligible to apply.
• Eligible Principal Investigators: Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institutions 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 support.
• See Section IV.1 for application materials.
• Telecommunications for the hearing impaired is available at: TTY 301-451-5936

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2.Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Receipt and Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Sharing Research Data
D. Sharing Research Resources
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
A. Cooperative Agreement Terms and Conditions of Award
1. Principal Investigator Rights and Responsibilities
2. NIH Responsibilities
3. Arbitration Process
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Purpose of this RFA

This Request for Applications (RFA) from the National Institute on Drug Abuse (NIDA) announces a limited competition for competitive cooperative agreement renewal applications from established clinical investigators to participate in the National Drug Abuse Treatment Clinical Trials Network (CTN). The competition is restricted to only those institutions that currently house an active Node in the CTN. This RFA is the fifth solicitation for participation in the CTN.

As a nation-wide partnership among drug abuse treatment providers, researchers, and NIDA staff, the mission of the CTN is to improve the quality of drug abuse treatment throughout the country using science as the vehicle. The CTN provides an enterprise in which community-based service providers, treatment researchers, and NIDA cooperatively develop, validate, refine, and deliver new treatment options to patients in community-level clinical practice. This unique partnership aims to achieve the following objectives:

o Conducting studies of behavioral, pharmacological, and integrated behavioral and pharmacological treatment interventions of therapeutic effect in rigorous, multi-site clinical trials to determine effectiveness across a broad range of community-based treatment settings and diversified patient populations;

o Facilitating the transfer of research results to physicians and other clinicians, providers, and patients.

CTN clinical trials could be carried out in a variety of settings, including community-based treatment settings, specialty clinics, physician offices or other venues that are not considered research intensive. 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. Awardees deliver and test an array of both behavioral and pharmacological treatments and determine conditions under which treatments can be effective. 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 (two sites), Connecticut, Florida, Maryland, Massachusetts, New Mexico, New York (two sites), North Carolina, Ohio, Oregon, Pennsylvania (two sites), South Carolina, Texas, and Washington. NIDA recognizes a benefit in broadening the types of treatment providers who participate in the network and encompassing more subpopulations of minority groups under study, thereby attaining greater variety in the types of studies conducted and greater confidence in the generalizability of those studies.

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 nodes 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 three additional sites were awarded in California, Massachusetts, and New Mexico. In 2005 nine nodes received competing continuation awards (California, Connecticut, Florida, New York, Ohio, Oregon, Maryland, Pennsylvania, and South Carolina) and two additional nodes were awarded in Pennsylvania and Texas. 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. Under the current RFA, NIDA seeks to expand the network to include additional different types of treatment settings. Applicants are encouraged to seek collaborations that combine activity with existing Nodes or to bring in new regions such as Alaska, the rural South, and urban, suburban, and rural areas of the Mid-West.

Strong partnerships and bi-directional collaboration between researchers and practitioners are essential and defining characteristics of the CTN as it develops and conducts large scale multi-site clinical treatment studies in community based treatment programs (CTPs). Through these partnerships and collaborations, the CTN seeks to accelerate the pace of research that is most relevant to drug abuse treatment practice as well as the application of research outcomes in a variety of treatment settings. Knowledge gained through the CTN is also expected to further the dissemination and the adoption of research-based treatments. That is, CTN research will identify effective treatments and can also help to inform the process of implementation and adoption to ensure the acceptability and sustainability of these new approaches.

Over the past seven years, the CTN has made progress toward: (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 dissemination and implementation of effective and useful interventions into its community-based drug treatment settings and (3) providing unique opportunities to train clinical researchers. At the present time, twelve protocols have been completed, eight have completed enrollment and are in the follow-up phase, and five are currently enrolling participants. One protocol is under development; sites awarded under the current RFA will have the opportunity to participate in this protocol as well as the opportunity to develop, participate in, or lead additional research protocols. In addition, the established infrastructure of the CTN is available for researchers to use as a platform for conducting other drug abuse treatment research studies. A number of such CTN platform studies have been funded to date, as well as ancillary studies more directly linked to ongoing CTN trials. Further details on the current status of the CTN may be found on the NIDA web site at: http://www.nida.nih.gov/CTN/Index.htm.

CTN Definitions, Organization, and Functions

Clinical Trials Network (CTN). A collaborative group of regional research Nodes working under a cooperative agreement award with NIDA to conduct multi-site, cross-regional (nationwide) clinical trials research on promising behavioral, pharmacological, and integrated drug abuse treatments. Specific research agendas for the CTN will emerge from a variety of sources, including RRTCs, CTPs and NIDA.

Node. A Node is the functional unit within the CTN, consisting of a Regional Research and Training Center (RRTC) and its affiliated Community Treatment Programs (CTPs). The RRTC arranges and coordinates the research partnerships among the RRTC and the CTPs. The CTN comprises multiple, geographically diverse Nodes.

Regional Research and Training Center (RRTC). The RRTC provides scientific leadership for the clinical trials conducted within the CTN and is an entity that resides within the grantee institution of the cooperative agreement award. The RRTC 1) establishes Node infrastructure, 2) collaborates with the CTPs to generate research and training agendas when requested, 3) provides administrative and operations support for trials, 4) builds partners with the CTPs, 5) collaborates with NIDA and other Nodes to develop, implement, and disseminate findings from CTN research projects, and 6) works cooperatively with the CTN Clinical Coordinating Center and Data and Statistics Center. Specifically the RRTC will be responsible for:

• Infrastructure. Infrastructure refers to the physical and operational capacity to 1) arrange and manage collaborative activities of at least three to five CTPs within the Node, 2) maintain scientific and technical personnel for protocol development and implementation, and 3) coordinate and provide resources for CTN activities that occur within the Node.
• Research Agenda. In close partnership with the CTPs within its Node and with colleagues across the CTN, RRTCs develop research concepts for potential CTN trials and submit them to the CTN Steering Committee for discussion and review. The research team, lead by one or more RRTCs, will propose a Lead Investigator (LI) for the study. NIDA scientific and technical personnel will be designated as collaborators on the project development and implementation team. The project team should include personnel and experts from across the network.
• Training Agenda: The CTN structure provides many opportunities for pre-doctoral, post-doctoral and junior faculty researchers to gain valuable experience in designing, participating in, and managing complex clinical trials. Accordingly, NIDA strongly encourages the RRTC to assist these and other practitioner-investigators to apply for separate awards under the training grant mechanisms supported by NIDA (e.g., T, K, and F awards).
• Administrative and Operations Support. The RRTC ensures appropriate administrative and operational support for Node activities, including but not limited to the conduct of trials. The support must ensure adherence to the Terms and Conditions of the Award and the policies and procedures of NIDA and the CTN as specified in the CTN Bylaws (http://www.nida.nih.gov/CTN/Structure.html).
• 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 during the process of developing research concepts and conducting trials, and 3) support for CTP participation in relevant CTN activities and operations.

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

Community Treatment Programs (CTPs). CTPs affiliated with the CTN over the first seven years typically have been drug abuse treatment programs in community settings that provide treatment to large and diverse patient populations. NIDA now broadens this definition to Page: 3
include additional service entities such as private practices, specialty clinics, and other entities outside the traditional drug abuse treatment practice. The term CTP is used to encompass this broader spectrum. Potential CTPs must have the capability for and interest in participating in controlled clinical trials.

Working as an equal partner with its RRTC, each CTP agrees to:

• Designate the Director of the CTP or a senior official of the CTP who reports directly to the Director to represent the CTP for CTN activities and to ensure fulfillment of CTP obligations during the course of a specific trial;
• Participate fully in the development of research concepts and protocols for trials to be conducted in the CTN;
• Participate in controlled clinical trials, including randomization methods for assignment of patients and/or therapists to different experimental or control conditions;
• Screen and recruit adequate numbers of patients required to meet the goals of the protocols in which they participate;
• Provide appropriate clinical care (i.e., experimental, standard, treatment-as-usual) to patients participating in 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 NIDA’s Clinical Coordinating Center and Data and Statistics Center;
• Maintain confidentiality of research data and
• Cooperate with periodic on-site audits by representatives of NIDA or its designees to ensure appropriate use of investigational drugs; compliance with regulations for IRB approval and informed consent (e.g., 45 CFR 46); compliance with protocol specifications; quality assurance and accuracy of data recording; and completeness of reporting of adverse drug reactions.

CTN Steering Committee. The Steering Committee constitutes the primary governing body of the CTN. Voting members are the Principal Investigator and one CTP representative from each Node, the CCTN Director or Deputy Director, and one representative each from the CTN Clinical Coordinating Center and CTN Data and Statistics Center. The Steering Committee uses both established and ad hoc committees and workgroups (e.g., Executive Committee, Research Development Committee, Research Utilization Committee, Publications Committee) to assist it in carrying out its functions. By accepting a Cooperative Agreement award, all participating RRTCs and CTPs must agree to abide by the policies and By-laws approved by the Steering Committee.

Protocol Review Board. An independent expert board, appointed by and reporting to the NIDA CCTN Director, that reviews proposed protocols and informed consent documents. To minimize delay and provide continuity, this board may be combined with a DSMB (see below) for a given study.

Data and Safety Monitoring Board (DSMB). An independent expert board, appointed by and reporting to the NIDA CCTN Director, 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 may also conduct a scientific review of the protocol if necessary (see above). The DSMB 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 a non-voting administrator of the DSMB.

Data and Statistics Center (DSC). The entity established under a contract awarded by NIDA to provide clinical data management systems as required to implement standards established by NIDA CCTN. Such standards guide development and implementation of the protocol-specific electronic data capture (EDC) system that each Node must implement at participating CTP sites.

The major tasks of DSC are to:

• Establish systems for the collection, management and storage of study data
• Design and perform all statistical analyses
• Review and monitor the quality of study data
• Monitor trial progress
• Prepare reports for the DSMB
• Provide data management and statistical support for protocol development
• Provide other expert consultation and support services as needed and directed by NIDA

Clinical Coordinating Center (CCC): The entity established under a contract awarded by NIDA to provide certain resources and common services for CTN clinical trials, including support for regulatory requirements and oversight functions mandated by NIH and DHHS.

Specific functions of the CCC include:

• Regulatory affairs support and Investigational New Drug (IND) filing, monitor IRB submissions, review Informed Consent forms;
• On-site monitoring of clinical study sites, quality assurance support, NIDA's safety officer for CTN trials;
• Central pharmacy services for medication packaging and shipping, inventory control, confirmatory analyses of study materials;
• Clinical laboratory support and drug testing, evaluation of new drug detection products, information on drug testing/screening methodology;
• Coordinate the distribution of trial supplies, medications, forms, and manuals;
• Provide regulatory, QA and training plans for protocols;
• Provide training in a variety of venues;
• Collaborate with the DSC to provide data for reports to the DSMB; and
• Provide other expert consultation and support services as needed.
• Logistic Support Center (LSC). The entity established under a contract awarded by NIDA to support many of the administrative and logistic functions of the CTN including:
• Coordinating logistic and operational support for CTN meetings and conference calls;
• Support for consultants providing NIDA and CTN grantees with expert advice;
• Preparing publicity, meeting, and protocol related materials as required;
• Creating and maintaining administrative databases to support CTN activities; and
• Maintaining a CTN web site.

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.

Research Protocol Development within the CTN. A protocol executive committee will be formed to develop and implement the protocol for each approved concept. NIDA scientific and technical personnel will serve on the protocol executive committee and on the project development/implementation team. Staff from the Data and Statistics Center and the Clinical Coordinating Center will consult to and collaborate with the protocol executive committee throughout the development and implementation process. Typically, the chair of the protocol executive committee will serve as the Lead Investigator (LI) of the trial. The LI assumes responsibility for all aspects of that specific trial and serves as the primary liaison to trans-CTN entities 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. The LI will be responsible for providing all 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.

Objective and Scope

The overall goal of the National Drug Abuse Treatment Clinical Trials Network is to improve the quality of drug abuse and addiction treatment throughout the Nation using science as the vehicle.

Specific objectives include:

• Supporting rigorous, multi-site clinical trials of efficacious behavioral, pharmacological, and integrated behavioral and pharmacological treatment interventions in community-based or specialty treatment programs to determine effectiveness across a broad range of treatment settings and patient populations.
• Supporting efficacy trials of promising theoretically grounded interventions in hard-to-recruit patient populations that must use multi-site designs to enhance the recruitment.
• Facilitating research on drug abuse and development of comprehensive drug abuse treatment programs that integrate co-occurring medical and mental health conditions (e.g., mental disorders, chronic non-malignant pain, HIV, Hepatitis B & C, tuberculosis, sexually transmitted diseases (STDs) and other blood-borne infections).
• Furthering the development of effective treatments by integrating behavioral and pharmacological interventions.
• Ensuring that treatment research in drug abuse and addiction is extended to a wider community, such as minorities, women, children, adolescents, underserved populations, and other special populations, patients with co-occurring psychiatric or medical conditions or including court-involved patients.
• Fostering the collaboration between practitioners and treatment researchers by encouraging practitioner involvement in developing research questions and by providing opportunities for bi-directional education, exchange of ideas, information, and values.
• Exploring the effectiveness of behavioral, pharmacological, and integrated behavioral and pharmacological treatment interventions to reduce the transmission of HIV and other diseases (such as hepatitis B and C or sexually transmitted infections) and to enhance adherence to treatment for HIV and other diseases among drug users. Additionally, small efficacy trials of promising, theoretically grounded behavioral interventions may be conducted.

CTN to date

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 RRTCs have demonstrated expertise in conducting drug abuse treatment research, clinical trials and clinical training. Through its associated CTPs, each Node demonstrates the capacity to recruit and treat a broad range of patients, including adolescents, women, patients with co-occurring mental and/or physical disorders, those at high risk for HIV infection, members of minority 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 tested and decisions concerning protocol design.

Completed CTN trials include studies on:

• Buprenorphine/Naloxone combination for opiate detoxification
• Motivational incentives (contingency management) to enhance drug abuse recovery
• Motivational interviewing to improve substance abuse treatment engagement and outcomes
• Motivational enhancement therapy to improve substance abuse treatment engagement and outcomes
• Smoking cessation treatment in substance abuse programs
• Organizational and staff characteristics of CTN CTPs
• Telephone contact procedures to improve continuing care engagement
• Characteristics of CTN CTPs policies and services to address HIV, HCV and STDs
• Impact of staff performance feedback on drug treatment outcomes

Ongoing CTN trials include studies on:

• Buprenorphine/Naloxone combined with psychosocial therapy for heroin addicted adolescents and young adults
• Seeking Safety intervention for substance abusing women with PTSD
• HIV/HCV risk reduction strategies in drug detoxification and treatment settings
• HIV/STD risk reduction strategies for men and for women in drug treatment programs
• Job training program for recovering drug users
• Motivational enhancement therapy for Spanish-speaking drug users
• Motivational enhancement therapy for pregnant drug users
• Brief strategic family therapy to reduce adolescent drug use
• Osmotic-release methylphenidate for ADHD in adolescents with substance use disorders
• Osmotic-release methylphenidate for adult smokers with ADHD
• Comparison of Buprenorphine/Naloxone and Methadone treatments on liver function and reduction of substance abuse
• Individual drug counseling in combination with Buprenorphine/Naloxone for treatment of prescription opioid analgesics

Further details on past and current CTN trials are available on the CTN website (http://www.drugabuse.gov/CTN/research.html).

Research concepts and questions for potential future CTN trials will be developed through a close partnership among the scientific leaders within the RRTCs and the clinical leaders within the CTPs. Selection of specific concepts to be conducted as CTN trials will occur through a collaborative effort between CTN grantees and NIDA.

Furthermore, as the CTN continues to evolve, NIDA encourages investigators both within and outside the existing network to propose additional research questions that can be answered through studies funded under separate research grants that are either proximally or distally related to the broader CTN trials and use the CTN infrastructure or trials as a platform. Examples include but are not restricted to:

• Techniques for transporting new behavioral therapies into community-based treatment groups.
• Optimizing access to and effectiveness of approved pharmacotherapies for treatment of drug abuse and addiction.
• Behavioral interventions aimed at improving adherence to medication regimens in patients with co-occurring addictive and mental or physical disorders.
• Effective therapies for treating marijuana, cocaine or methamphetamine abuse -- particularly in adolescent and young adult populations.

In the area of research on HIV/AIDS, and other infectious diseases, specific examples include, but are not restricted to:

• Simple and effective behavioral approaches to improve outreach efforts and reduce risky behaviors.
• Impact of drug abuse treatment on AIDS related outcomes, such as rate of progression to AIDS, or on outcomes related to Hepatitis B and C.
• Interactions between medications used to treat drug abuse and those used to treat HIV, Hepatitis, and sexually-transmitted diseases.
• Interactions between screening practices for drug abuse and those for HIV/AIDS, Hepatitis, or sexually-transmitted diseases.
• Prevention of HIV infection in drug abuse and in health-disparity populations.
• Implementation and access to drug abuse treatments in HIV clinics.
• Methods to track adherence for HIV and for drug abuse treatments
• Co-morbid conditions in patients with HIV who use drugs of abuse.
• Strategies for capacity building and cost-effectiveness of prevention, diagnosis and treatment.

The CTN, with its core of CTPs engaging diverse populations, can provide a vehicle to recruit study subjects for such related topics as the genetic vulnerability to addiction health service research and studies of patients with co-occurring mental and/or physical disorders.

In the area of genetics, specific examples include, but are not restricted to:

• Studies that better describe and predict the complex nature and course of drug abuse and addiction in order to offer more precise phenotypic indices for testing of hypothesized underlying genetic risk factors associated with drug abuse.
• 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).
• Studies that enhance the ability to collect genetic specimens across large-scale, multisite trials
• Studies that use longitudinal designs to examine the nature and impact of genetic factors
• Studies that develop and evaluate methods to genotype participants in clinical trials
• Projects that advance the use of storage facilities for data on genotyping

In the area of health service research, NIDA encourages researchers to study treatment issues at the organizational and program levels. Specific examples include, but are not restricted to:

• Research that examines the economic impacts and outcomes of drug abuse treatment interventions, including cost effectiveness, cost-benefit, and cost offset studies.
• Studies that examine and describe systems-level factors such as organizational, management, staffing, and financial arrangements that affect the accessibility, quality, cost, outcomes, and delivery of drug abuse services. Examples may include studies to improve the consistency of management and reduce the currently high rates of staff turnover; studies that predict factors that expand the receptivity, willingness, and ability of treatment providers and organizations to implement evidence-based practices; and studies to describe and test components of leadership and management that facilitate the implementation, and sustainability of evidence-based treatment services.
• Studies that focus more closely on efforts to improve practice on both systemic and individual levels. Examples may include research that describes and predicts the complex reimbursement schemes involving state, local, and third party payers and research on promising innovations in financing policy and practice.

In the area of co-occurring medical, psychiatric, and addictive conditions, specific examples include, but are not restricted to:

• Studies that would increase understanding of how patients with multiple co-occurring conditions may be recruited and engaged in randomized clinical trials
• Strategies to increase treatment retention and research follow-up response rates among patients with co-occurring conditions

In the area of instrument development, specific examples include, but are not restricted to:

• Projects that would simplify, automate, standardize, or reduce the cost of administration of clinical research instruments used in CTN trials
• Projects that would reduce error rates in completing assessment or clinical instruments and in transmitting data to data management entities
• Projects to develop instruments that measure factors relevant and important to the conduct of addictions research, such as: the extent of craving and/or of withdrawal, the risk of addiction to a particular substance, the therapeutic alliance between patient and therapist, perceived satisfaction with health care, probabilities of a pain management patient developing dependence/abuse on pain medications, and probability of successfully completing detoxification
• Projects to develop instruments that measure and predict HIV risk behaviors

In the area of bio-marker development, specific examples include, but are not restricted to:

• Projects that develop and evaluate innovative diagnostic drug screening tests for drug abuse, such as oral swabs
• Projects that develop and evaluate the use of gene chip technology for drug abuse risk factors
• Projects that develop and evaluate the use of proteomic technologies for identifying post expression changes in major CNS proteins

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

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

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

1. Mechanism(s) of Support

This funding opportunity will use the NIH U10 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 VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award". This RFA is a one-time solicitation.

2. Funds Available

NIDA expects to make up to 3 to 6 competing continuation grants under this RFA for project periods of up to 3 years of support. It is expected that each Node will have an operating budget of up to $1.25 million total costs per year. Costs for specific protocols are managed centrally at NIDA and dispersed as supplements to the U10 grants. Requested budgeting for future years of the U10 award should reflect core support only. The anticipated award date for this RFA is August 31, 2007. NIDA intends that the Nodes to be funded under this RFA will have the same project end date as the eleven Nodes that will complete their project periods in FY 2010. It is anticipated that there will be subsequent RFAs to sustain or expand the CTN, with all existing Nodes recompeting on the same cycle, subject to availability of funds.

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.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

Eligible organizations include only those organizations and institutions that currently house an existing, active Node in the National Drug Abuse Treatment Clinical Trials Network (CTN). Foreign institutions are not eligible to apply.

1. B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with an eligible 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 support. The Principal Investigator must commit to and be actively involved in the research and governance of the CTN at a significant level of effort, typically between minimum of 35 percent effort and a maximum of 65 percent effort. PIs must document a substantial history of leadership in clinical trials research and an extensive research publication record.

2. Cost Sharing or Matching

Cost sharing is not required.

The most current Grants Policy Statement can be found at: http://grants.nih.gov/grants/policy/nihgps_2003/nihgps_Part2.htm#matching_or_cost_sharing

3. Other-Special Eligibility Criteria

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 a significant level of effort to this project, as described above.

Section IV. Application and Submission Information

1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: [email protected].

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates
Letter of Intent Receipt Date(s): October 28, 2006
Application Receipt Date(s): November 28, 2006
Peer Review Date(s): February - March, 2007
Council Review Date(s): May - June 2007
Earliest Anticipated Start Date: August 31, 2007

3. A.1. Letter of Intent

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

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

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:

DA-07-001
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: [email protected]

3. B. Sending an Application to the NIH

Applications must be prepared using the research grant applications found in the PHS 398 instructions for preparing a research grant application. 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
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

DA07-001
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: [email protected]

Using the RFA Label: The RFA label available in the PHS 398 application instructions 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.

3.C. Application Processing

Applications must be received on or before the application receipt date (November 28, 2006) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by NIDA. Incomplete and non-responsive applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity 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 a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity 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.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing continuation award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.

6. Other Submission Requirements

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 currently approved version of the PHS 398 with the exceptions noted below.

PHS 398 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, described as sections 1 6 below, and conform to the 45 page limit described in a subsequent section of this announcement. The section on Human Subjects Research (referred to as research plan section e in the PHS 398 application kit) and other sections described below, including the budget section, should follow section 6 and are not counted within the 45 page limit

Specific Requirements for Applications

1. Progress Report Section

It is recognized that each 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. Applications must also include a copy of all periodic performance reviews generated by the CCTN and transmitted to the Node. An application must include a progress report that at minimum consists of:

• An analysis of the Node performance reviews generated by the CCTN and transmitted to the Node (a copy of all Node performance reviews generated by the CCTN must be included in section 8 as described below) ;
• Evidence of efficient administrative structure/personnel in managing multi-site trials and of the ability to participate in multi-site trials;
• A summary of research activities and accomplishments during the prior funding period, including a clear presentation of annual accrual to all participating protocols, the gender/ethnic minority composition of recruited study populations from affiliated CTPs, and how well accrual met CTN accrual goals;
• Documentation of scientific productivity as reflected in scientific publications and presentations pertaining to CTN activities;
• Description of efforts in facilitating dissemination, implementation, and adoption of CTN results for affiliated CTPs;
• Progress in developing and implementing research protocols, including details of the process and organizational structure for protocol development and implementation, training activities with CTP and other Node staff, and effective site management.;
• Evidence of ability to engage community treatment programs in bi-directional communications to bridge the research to practice gap;
• Evidence of participation and leadership in CTN research and administrative activities;
• Summary of unique contributions of the Node to CTN-wide activities in the prior funding period.

2. Understanding of and Ability to Contribute to the Mission of the CTN: This section should establish the applicant’s understanding of the CTN and describe how the proposed Node contributes to the CTN goals.

3. Administrative and Management Plans: The qualifications and experience of the Principal Investigator must be described. An individual should be designated as the Node coordinator for research activities within the Node; his or her qualifications and experience should also be described. Each application must also demonstrate the ability to engage collaborators with the appropriate expertise to design and implement the proposed interventions and controlled clinical trials.

It is important to demonstrate the Principal Investigator’s ability to contribute to the CTN’s scientific agenda and commit the level of effort required to provide appropriate leadership. 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. The selection of diverse CTPs for CTN participation should be evident.

Plans for organizational and communications structures encompassing the Node's CTPs should be specified. Diagrams and descriptions of proposed 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.

4. Research and Clinical Infrastructures

Descriptions should document the availability of appropriate expertise within the RRTC to design and implement any proposed trials.

In addition, they 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 within-Node activities. The plans should also elaborate on the infrastructure capabilities in protocol design, research administration, project and site management, and publication of results. A description of the framework and procedures for training and supervision of treatment providers in the experimental and comparison interventions that will be utilized in the CTN should also be evident.

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

5. Collaborations between the RRTC and CTPs

The application should describe the relationships among the CTPs and the RRTC. It should provide detailed descriptions of CTPs that will participate, including patient population characteristics, patient throughput, types of treatment currently delivered, staff size and characteristics, and organizational structure. Applications should use the 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. Letters of agreement from CTP directors and additional tables as needed to describe the CTPs should appear in the application appendix.

For each proposed Community Treatment Program (CTP):

a. Name of Organization

b. Address

c. Telephone

d. Fax Number

e. Director/Contact (person who will work with the CTN, serve on committees, etc.)

f. E-Mail Address of Director/Contact

Characteristics of each CTP to include:

a. Number of clinical sites in organization

b. Static capacity -- at any one time, what is the CTP’s total patient census?

c. Annual patient admissions by treatment modality

d. Rural, suburban or urban setting

e. Clinic patient characteristics:

• Percent Black, African-American
• Percent Hispanic, Latino
• Percent White, Caucasian
• Percent American Indian or Alaskan Native
• Percent Asian or Pacific Islander

f. Gender breakdown of patients -- percent male, percent female

g. Age breakdown of patients -- percent adolescent (younger than 21), percent over 65 if known

h. Special populations served.

i. What kinds of HIV/HCV services are currently offered?

• Education and prevention
• testing and counseling
• treatment for HIV/HCV

j. Does the CTP offer pharmacological treatments? If so, which medications?

k. Does the CTP offer behavioral treatment? If so, what types of treatment are offered? Is treatment provided in individual or group sessions, or both?

l. Categorize setting as:

• Outpatient
• Residential
• Post-residential
• IOP (Intensive Outpatient Treatment)
• TC (Therapeutic Community) -- treatment beyond the standard 6-8 week program
• Day care -- all day 8-5, 5 days per week.
• Half-way House

m. Does the CTP treat patients with co-occurring disorders?

n. Are faith-based treatment services part of the program? If so, please describe.

o. Primary source of program funding: Patient Fees, Public Insurance, Public grant or contracts, Private Insurance.

p. 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 within sections 1 - 6 (i.e., within the 45 page limit). 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. http://grants2.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm

6. Research Concept:

Applicants should provide a specific example of a research concept and an abbreviated research plan, consistent with the RFA, which could be carried out to take advantage of the unique capabilities of the CTN, including collaboration across Nodes. This concept plan is not expected to be a detailed research protocol. Nevertheless, the concept should present a discussion of the types of research questions that could be addressed, the relevance and feasibility of these questions to community treatment providers, 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 how the Node will be able to work collaboratively with other Nodes and NIDA in multi-site clinical trials. Over the next few years the CTN expects to be especially interested in considering the merits of concepts of large, simple trials that engage large numbers of CTPs and will significantly impact the nation’s public health. It should be understood that the concept example will not necessarily be implemented in the CTN. Specific research concepts do not need to undergo IRB review for the purposes of this application; however, all protections, policies, and requirements for human subject research must be followed if a concept is selected for implementation at a later time.

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; information on human subjects protections; and potential dissemination and implementation efforts. Finally, there should be a cost estimate displayed as a protocol budget.

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

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

8. Node Performance Reviews

CCTN periodically generates Node performance reviews and transmits them to each active CTN Node. As stated above, an analysis of these reviews must be included in the Progress Report (section 1). A complete copy of all such reviews must be submitted in section 8. As noted above, section 8 is not subject to the 45 page limit.

9. 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. Detailed individual and overall 3-year summary composite budgets are required for each individual project, component and or sub-recipient (i.e., infrastructures, CTPs, consortiums, etc.). These detailed budgets should identify the sub-recipient's name, if different from the grantee, and include applicable narrative budget justification for items requested in order to preclude disallowance of costs. In addition, an overall 3-year composite summary budget incorporating all costs requested in the project period by category is required.

Page Limits

To summarize the guidance above, the total length of sections 1 - 6, 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.

Plan for Sharing Research Data

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.

The Awardee also agrees to cooperate with NIDA’s contracted Data and Statistics 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.

The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.

The following will be considered in making funding decisions:

• Scientific merit of the proposed project as determined by peer review
• Availability of funds
• Relevance of program priorities

2. Review and Selection Process

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 complete and responsive applications will:

• Be discussed and assigned a priority score.
• Receive a written critique.
• Receive a second level of review by the National Advisory Council on Drug Abuse.

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an 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.

Significance: Does this study address an important scientific health problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

• Does progress indicated in the application indicate active and engaged participation in CTN trials and in other CTN activities?
• 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)?
• To what extent would the proposed Node likely contribute or continue to contribute to the goals and enhance the capability of a nationwide CTN?
• Will the study improve the treatment on the hard-to-recruit patient populations (e.g. co-morbid, HIV/AIDS, Hepatitis B & C, tuberculosis and other at risk populations)? Will the proposed studies impact the treatment interventions to reduce the transmission of HIV and other diseases (such as hepatitis B and C or sexually transmitted infections) and enhance adherence to treatment for HIV and other diseases among drug users?
• Will the study foster the collaboration between practitioners and treatment researchers?
• If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? Is this Node likely to advance the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

• How has the Node contributed to protocols, trials, research dissemination or other measures of Node performance in the last period of funding?
• 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?
• 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?
• How strong are the plans for effective interaction and coordination with other Nodes and NIDA?
• Does the application demonstrate a capacity to manage CTPs across state boundaries and geographic regions?
• Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project?
• Does the applicant acknowledge potential problem areas and consider alternative tactics?
• Does the study propose comprehensive treatment programs that integrate co-occurring medical and mental health conditions for at-risk populations?
• Does the study propose treatment programs for at risk communities such as minorities, women, children, adolescents, underserved populations, and patients with co-occurring psychiatric or medical conditions or including court-involved patients.
• Does the study encourage and provide opportunities, for bi-directional input from practitioner and treatment researchers?
• Does the study propose evaluative approach for efficacious behavioral, pharmacological, and integrated behavioral and pharmacological treatment interventions?
• How well developed are the RRTC's criteria for selecting CTPs with diverse population and treatment representation (as balanced by constraints of reasonable management)?
• To what extent do the proposed CTPs vary programmatically? To what extent are they able to accrue a demographically diverse patient population?
• 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?
• What is the quality of plans for involving CTPs in the research and organizational activities of the CTN? Does the approach expand and broaden the types of treatment providers who participate in the network?
• Do the CTP plans expand and broaden the geographic distribution of currently-funded CTN sites?
• Do the CTP plans expand and broaden the subpopulations of minority groups studied?
• How well does the proposed research concept demonstrate knowledge of state-of-the-art research designs, methodologies, and operations? Does the proposed concept have the potential to produce a major improvement in the quality and effectiveness of drug treatment?
• Does the application bring unique strengths or limitations to the CTN as a whole?

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area? Does the study propose new and innovative treatment modalities?

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

• Is there evidence that the Node has achieved goals during the past funding period?
• Is there sufficient evidence that the proposed Principal Investigator (PI) will have (or has devoted) adequate time to carry out the work of the CTN?
• 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?
• 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

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

• How good are the available resources and proposed personnel for administering Node participation in clinical trials, and assure the safety of patients/participants?
• 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?
• How strong is the Node s capacity to conduct research on HIV/AIDS and substance abuse?
• How good are the quality of the proposed CTPs and the experience of their program directors?

PROGRESS: (For competing continuation applications):

o Has there been adequate progress in RRTC-CTP collaborations, 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 Has there been progress in developing and implementing protocols?

o Has there been success in subject accrual and retention?

o Has there been progress in implementing evaluation of Node activities?

o Have there been appropriate levels of publications/presentations of research findings?

o Have there been appropriate levels of participation and leadership in CTN-wide protocols?

o Have there been appropriate levels of participation and leadership in CTN-wide committees?

o Has this node brought unique strengths or limitations to the CTN as a whole?

2. A. Additional Review Criteria:

In addition to the above criteria, in accordance with NIH policy, all applications will also be reviewed with respect to the following:

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 the Research Plan, Section E on Human Subjects in the PHS Form 398).

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 will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

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 Form 398 research grant application instructions will be assessed.

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. How appropriate budget estimates are for CTP support. How adequate plans are for budgetary control and oversight? The priority score should not be affected by the evaluation of the budget.

2. C. Sharing Research Data

Data Sharing Plan: 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 the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.

2.D. Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps/part_ii_5.htm#availofrr and http://ott.od.nih.gov/policy/rt_guide_final.html<span class=regulartext>). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

3. Anticipated Announcement and Award Dates

N/A

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Also Section IV.5. Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2. A. Cooperative Agreement Terms and Conditions of Award

The following 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 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement (NIH U 10), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined above.

2.A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator (PI) will have the primary responsibility for defining the details for the project within the guidelines described in the Request for Applications DA-07-001 and for performing the scientific activity. PIs 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 PI further agrees to accept close coordination and to cooperate fully with NIDA designated coordinating centers and contractors that will be responsible for implementing approved protocols. The PI further agrees to participate fully in the activities of the Clinical Trial Network (CTN) Steering Committee and in other committees and workgroups as formed.

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).

a. Responsibilities of the CTN Regional Research and Training Center (RRTC):

Generally, Awardees under this agreement have the following rights and responsibilities as a National Drug Abuse Treatment Clinical Trials Network (CTN) RRTC:

• The RRTC builds partnerships with the CTPs and provides scientific leadership and management of clinical trials as well as administrative and study operations services for the Node. The RRTC agrees to negotiate and establish formal relationships with three to five community treatment programs (CTPs) to participate in CTN activities and conduct research and training projects. These agreements will 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. Initial agreements between the RRTC and the CTPs may need to be more general as specific details will depend on the particular research projects that are conducted in each CTP.
• Infrastructure for core functions This includes but is not limited to 1) arranging and managing the participation of three to five CTPs; 2) maintaining scientific and technical personnel for protocol development and implementation; 3) coordinating and providing resources for activities within the Node; 4) collaborating with NIDA and other Nodes to develop, implement, and disseminate findings from CTN research projects; and 5) working with the CTN Clinical Coordinating Center and Data and Statistics Center. The Steering Committee meets two (2) times each year. The Principal Investigator agrees to provide adequate support for RRTC and CTP participation in Steering Committee and other CTN meetings as required.
• Research Concept Development and Implementation - In close partnership with the CTPs, and in collaboration with other CTN members, the RRTC develops research concepts for potential CTN trials and submits them to the CTN Steering Committee for discussion and review, and to NIDA for approval.

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 (LI) 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 study’s outcomes and ensure its broader utilization by the drug abuse treatment community while maintaining subject confidentiality.

The Awardee also agrees to cooperate with NIDA’s contracted Data and Statistics 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.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

c. Quality Assurance and Site Management:

The RRTC and participating CTP are responsible for the proper conduct of CTN studies at their site and must appoint qualified staff to perform site management activities. All clinical trials are subject to quality control as stated by the ICH Good Clinical Practice (GCP) guidelines. Each RRTC and participating CTP must agree to periodic on-site visits by staff from the Node and the NIDA appointed Coordinating Centers to perform the following: use of investigational drugs; compliance with regulations for Institutional Review Board (IRB) approval and informed consent (compliance with 45 CFR 46); compliance with protocol specifications; quality control and accuracy of data recording; and completeness of reporting adverse events. Reports of such on-site audits will be reviewed by the CCTN. In addition, NIDA program and grants management staff will review protocol accrual, and fiscal and administrative procedures.

d. 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: 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).

Final Study Report: Lead Investigators are required to provide 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. In addition, The Lead Investigator will make present primary outcome results to the trial DSMB prior to publication.

e. 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. The Awardee agrees to present all CTN manuscripts to the Publications Committee for review and approval prior to journal submissions.

f. 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; 6) emergence of new information that diminishes the scientific importance of the study question; 7) misuse of federal funds; and 8) serious shortfalls in appropriated funds available to pursue the study. Financial support from NIDA and access to further investigational drug supplies through this cooperative agreement will cease upon project closure, except that funds and other resources may remain available for patients already enrolled in the study. .

2.A.2. NIH Responsibilities

The Center for the Clinical Trials Network (CCTN) is the organization within NIDA responsible for the scientific, administrative, and operational management of the CTN research program funded by NIDA. NIDA has established a Logistic Support Center (LSC) under a contract to support many of the administrative and logistic functions of the CTN.

NIDA staff has substantial scientific and programmatic involvement throughout this cooperative agreement through technical assistance, and advice and coordination extending beyond normal program stewardship for grants as described below.

a. NIDA’s Scientific Role

The Director of the NIDA CCTN will appoint CCTN Protocol Coordinators (CPC) with expertise in behavioral therapies, medications development, and practice research to participate in the development of study plans and protocols, and to coordinate projects across scientific disciplines and CTN Nodes. NIDA CPCs may initiate or participate in publications in accordance with established professional and NIH guidelines for authorship.

The NIDA CCTN Director or Deputy Director will be a voting member of the CTN Steering Committee.

The NIDA CCTN Director, and/or designated staff, will work closely with the CTN Steering Committee to assure that CTN efforts are consistent with NIDA’s research objectives and complement other clinical trial activities supported by NIDA under other means.

NIDA will serve as a resource, and will disseminate information regarding promising new therapies. NIDA staff will advise the clinical investigators, as requested or needed, of results from other trials (e.g., adverse experiences and study termination) that could influence the design, development, or conduct of clinical trials under this cooperative agreement.

NIDA will appoint advisory boards as deemed necessary during the development and progress of protocols and trials

For ongoing research projects NIDA personnel and its contractors will monitor the safety of study participants through review of incremental case report form. NIDA and its contractors 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). The DSMB may recommend to NIDA a need to alter, suspend, or close an ongoing trial due to safety concerns or study performance issues.

b. NIDA’s Role in Protocol Review and Approval

In order for a CTN research project to be initiated, a research concept must be mutually approved by the CTN Steering Committee and NIDA. Once a concept is presented for consideration, NIDA will evaluate the proposed trial according to NIDA’s treatment research agenda, potential impact on scientific or treatment parameters; relevance to current national priorities, likelihood for 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.

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.

c. NIDA Access to Data

The NIDA CCTN Director, and/or designated staff or agents, shall have access to all data generated under this cooperative agreement. Monthly reports on trial progress will be prepared by the DSC and reviewed by CCTN, the CTN Executive Committee, and the study Lead Investigator. 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.

Monitors from the Clinical Coordinating Center will perform periodic onsite review of data recorded on clinical source documents, case report forms, or in electronic form. The Clinical Coordinating Center (CCC) is established under a contract awarded by NIDA to provide certain resources and common services for CTN clinical trials, including support for regulatory requirements and oversight functions mandated by NIH and DHHS.

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 or publication by the CTN.

d. NIDA Monitoring of Trials

Monitoring of clinical trials is the regulatory responsibility of the study sponsor. All clinical trials are subject to monitoring; the RRTC and participating CTP must agree to periodic on-site monitoring visits by the Clinical Coordinating Center representatives. During the course of a clinical trial, monitoring is conducted to assure that: the rights and well-being of participants are protected; the reported trial data are accurate, complete, and verifiable from source documents; and the conduct of the trial is in compliance with the currently approved protocol/amendment(s), with GCP, and with applicable regulatory requirements.

e. NIDA Review of Performance

The NIDA CCTN Director will periodically review the performance of the CTN as a whole and of individual RRTCs. Such reviews will include periodic reviews of the RRTC and its CTP sites for compliance with clinical and regulatory guidelines and success in achieving established performance standards. The review will be based on information provided in periodic progress reports compiled from data on recruitment, retention, follow-up, treatment exposure, quality assurance, and other factors, as well as from 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.

f. Normal Program Stewardship

A separate NIDA Program Official other than the CTN director will be responsible for the normal programmatic stewardship of the award and be identified in the Notice of Grant Award.

2.A.3. Collaborative Responsibilities

CTN Steering Committee. The Steering Committee constitutes the primary governing body of the CTN. Voting members are the Principal Investigator and one CTP representative from each Node, the CCTN Director or Deputy Director, and one representative each from the CTN Clinical Coordinating Center and CTN Data and Statistics Center. The Steering Committee uses both established and ad hoc committees and workgroups (e.g., Executive Committee, Research Development Committee, Research Utilization Committee, Publications Committee) to assist it in carrying out its functions. By accepting a Cooperative Agreement award, all participating RRTCs and CTPs must agree to abide by the policies and By-laws approved by the Steering Committee.

Protocol Review Board. An independent expert board, appointed by and reporting to the NIDA CCTN Director, that reviews proposed protocols and informed consent documents. To minimize delay and provide continuity, this board may be combined with a DSMB (see below) for a given study.

Data and Safety Monitoring Board (DSMB). An independent expert board, appointed by and reporting to the NIDA CCTN Director, 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 may also conduct a scientific review of the protocol if necessary (see above). 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 a non-voting administrator of the DSMB.

2.A.4. Arbitration Process

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel composed of three members will be convened. The three members will consist of a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two. In the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding opportunity 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:

1. Scientific/Research Contacts:

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: [email protected]

2. Peer Review Contacts:

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: [email protected]

3. Financial or Grants Management Contacts:

Deborah S. Wertz
Grants Management Branch
National Institute on Drug Abuse/NIH/DHHS
6101 Executive Boulevard, Room 270
Bethesda, MD 20892-8403
Telephone: (301) 443-6710
FAX: (301) 594-6849
Email: dwertz@nida.nih.gov

Section VIII. Other Information

Required Federal Citations

Use of Animals in Research:
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). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, 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 and 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.

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 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 funding opportunity 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.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

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 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is 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 Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical 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 (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 applications for research involving human subjects and individuals designated as key personnel. The policy is available 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 (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.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

For more information about the Policy or the submission process please visit the NIH Public Access Policy Web site at http://publicaccess.nih.gov/ and view the Policy or other Resources and Tools including the Authors' Manual (http://publicaccess.nih.gov/publicaccess_Manual.htm).

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

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 www.nida.nih.gov under the Funding, or may be obtained by calling (301) 443-2755.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for 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 PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

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.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.

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