Part I Overview Information

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Department of Health and Human Services

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

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

Title: Medications Development Centers of Excellence (P50)

Announcement Type
This Funding Opportunity Announcement (FOA) is a reissue of RFA-DA-04-003.

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

• September 16, 2008 - See Notice (NOT-DA-08-040) The purpose of this notice is to change the expiration date.

Request For Applications (RFA) Number: RFA-DA-09-002

Catalog of Federal Domestic Assistance Number(s)
93.279

Key Dates
Release Date: August 27, 2008
Letters of Intent Receipt Date: November 19, 2008
Application Receipt Date: December 19, 2008
Peer Review Date(s): February/March 2009
Council Review Date: May 2009
Earliest Anticipated Start Date: July 2009
Additional Information To Be Available Date (Url Activation Date): Not applicable
Expiration Date: November 20, 2008 (New Expiration Date December 20, 2008 per NOT-DA-08-040)

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

• Purpose. This FOA issued by the National Institute on Drug Abuse, National Institutes of Health, solicits Center Grant (P50) applications to provide support for research centers (Medications Development Centers of Excellence) dedicated to clinical research directed towards the identification, evaluation and development of safe and effective medications for treatment of substance related disorders (SRDs), alone or with comorbid conditions. Research may focus on both currently approved and/or novel, investigational medications.
• Mechanism of Support. This FOA will utilize the P50 center grant mechanism.
• Funds Available and Anticipated Number of Awards. It is anticipated that $7,500,000 in total costs will be awarded to a total of 5-7 applications for this announcement.
• Budget and Project Period The size and duration of individual awards will vary as a function of the nature and scope of the research proposed. It is anticipated that the upper limit of each award will be $1,000,000 per year in direct costs, and applications over $1,000,000 per year in direct costs will not be accepted for review. Applicants may request a project period of up to five years.
• Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
• Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization 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.
• Number of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs) may be designated on the application as center director. In this case, each PD/PI will be considered a center co-director. However, individual projects are expected to be headed by a single investigator only.
• Number of Applications. Applicants may submit more than one application, provided they are scientifically distinct.
• Resubmissions. Resubmission applications are not permitted in response to this FOA.
• Renewals. Renewal applications will be permitted for this FOA.
• Special Date(s). This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates
• Application Materials. See Section IV.1 for application materials.
• Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY 301-451-5936.

Table of Contents

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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, Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
D. Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements and Information

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
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

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Section I. Funding Opportunity Description

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1. Research Objectives

Purpose

The purpose of this FOA is to solicit Center Grant (P50) applications to provide support for research centers (Medications Development Centers of Excellence (MDCEs)) dedicated to clinical research directed towards the identification, evaluation and development of safe and effective medications for treatment of substance related disorders (SRDs), alone or with comorbid conditions. Research may focus on both currently approved and/or novel, investigational medications. Under this FOA, applicants may focus on pilot Phase I safety/tolerability or Phase II or III efficacy studies; human laboratory studies on medication interactions with other drugs; pharmacokinetic or pharmacodynamic studies; or, if justified, multisite efficacy studies. Because the treatment of SRDs necessitates a multidisciplinary approach, optimal pharmacological treatments require a behavioral treatment strategy. Therefore, applications may propose the concurrent evaluation of pharmacotherapy and behavioral treatment approaches in an integrated design, whereby behavioral treatment components should provide a platform for the medication trials proposed.

Background

As part of NIDA’s strategic plan to significantly reduce SRDs, the discovery of safe and effective medications for the treatment of disorders related to the abuse of cocaine and other stimulants, as well as opioid, cannabis, and club drug related disorders, remains a top priority. This FOA solicits research on medications to treat a variety of aspects of the immediate and long-term effects of drug abuse and dependence, such as craving, relapse, and the physiological and behavioral consequences resulting from SRDs. NIDA has made the development of pharmacotherapies for unmet treatment needs, such as SRDs associated with cocaine, methamphetamine, and cannabis abuse, a top priority.

The NIDA Medications Development Program, aimed at identifying and screening new medications as potential pharmacotherapies, has focused on the involvement of neurotransmitter systems in cocaine craving and relapse and the identification and testing of entities which directly or indirectly modulate these systems (e.g., dopamine or serotonin receptor agonists and antagonists, pharmacotherapies that, directly or indirectly, through modification of GABA, glutamate, or endocrine systems, affect dopamine, serotonin, or noradrenergic transmission). Additionally, any target medication justified as potentially effective in modulating aspects of stimulant dependence through other mechanisms is also appropriate for study.

There is a critical need to address the growing problem of methamphetamine abuse and dependence. The increased HIV risk behaviors and transmission amongst methamphetamine abusers corroborates the need for safe and effective pharmacotherapies to treat methamphetamine abuse. The highly addictive nature of this substance, in addition to its low cost and ease of production, as well as the serious physiological and neurological consequences of its abuse, have made methamphetamine dependence a problem of major proportions. There are currently no pharmacological treatments for dependence on methamphetamine. Medications, which affect dopaminergic or noradrenergic systems, or that directly or indirectly modulate their neurotransmission, may be useful to test as treatment agents for amphetamine abuse. Additionally, strategies to reduce methamphetamine plasma concentrations or counteract its pharmacological effects could serve as a useful adjunct in the management of the acute medical and psychiatric symptomatology of methamphetamine overdose and methamphetamine-induced cognitive impairment.

The chronic use of cannabis has been shown to produce serious physical and psychological consequences. Chronic users may experience difficulty in stopping or controlling drug use, develop tolerance to the subjective and cardiovascular effects, and eventually present withdrawal symptoms after sudden discontinuation of use. Long-term heavy use may produce cognitive changes, including psychosis, and has been shown to affect the normal development of adolescence. There are currently no effective pharmacological treatments for cannabis use disorders and very limited research focused on the identification and development of medications to treat these disorders. Intensive preclinical research has produced a greater understanding of the basic mechanism of cannabis action, providing a foundation for hypotheses driven clinical research.

In addition to the above, the development of treatments for specific drug abusing populations is a programmatic priority. These include polydrug abusers, individuals with a co-morbid substance use and psychiatric disorder, pregnant addicts and their fetuses, neonates born to addicted women, adolescents, women, minorities, and individuals within the criminal justice system. The treatment of specific or vulnerable patient populations could either constitute the main focus of the research plan or be a component or components thereof.

Objectives and Scope

The major goal of this FOA is to provide support for research centers (Medications Development Centers of Excellence or MDCEs) dedicated to clinical research directed towards the development of pharmacotherapies for the treatment of substance related disorders, alone or with comorbid conditions, the top priority being areas of unmet clinical needs (stimulant- and cannabis-related disorders and the treatment of specific or vulnerable patient populations). The following are some examples of research themes that the MDCE might utilize:

Research Themes

• The development of medications for the treatment of a specific substance use or induced disorder, or induced disorders with or without other psychiatric comorbidities. For example, Phase I, II or III studies to develop a medication, or medications, for the treatment of cocaine or methamphetamine dependence.
• The targeting of neurochemical mechanisms implicated in substance abuse disorders, by the direct or indirect modulation of systems, such as: cathecolaminergic; glutaminergic; cannabinoid; GABA; opioid; endocrine (e.g., CRF); and/or multiple neurochemical systems.
• Paradigms to approach substance-related disorders, such as initiation of abstinence; relapse prevention; prevention of complications; intervention of surrogate variables of drug abuse.

Research Components

The purpose of the MDCE is to foster collaboration on cutting edge questions in the pharmacological treatment of SRDs. Preclinical research projects should not be proposed in response to this FOA. Some examples of research components may include, but are not limited to:

• The development and testing of new chemical entities for the treatment of SRDs.
• Phase I testing of the safety of new medications or medications previously approved for other indications that may be effective for the treatment of SRDs.
• Phase I testing of medications or combinations of medications, for which safety concerns may exist, or for which a safety assessment may be required by the Food and Drug Administration, before Phase II trials may begin.
• Phase II clinical trials testing the efficacy of medications using rapid screening methods (Phase IIa) or large scale, randomized, well-controlled clinical trials (Phase IIb).
• Multicenter clinical trials to test medications for specific clinical conditions for which it is difficult to recruit subjects in a timely manner at one MDCE.
• Testing of potentially additive or synergistic neurochemical mechanisms using one medication with action in multiple mechanisms of actions, or combinations of medications each targeting a different mechanism.
• Development of new human laboratory models for evaluation of medications for relapse prevention, initiation, and abstinence.
• Developing and testing new paradigms of treatment success.
• Optimizing the safety or efficacy of approved medications for SRDs by testing them in specific patient populations.
• Testing drug-drug interactions between medications for treatment of SRDs and other drugs/medications, including but not exclusively, illicit drugs, anti-retroviral medications, anti-psychotic medications, etc.
• Increasing the diversity of populations in whom the medications are tested by increasing the representation of women and minority groups in clinical trials or by designing clinical trials that specifically address the treatment needs of those groups.
• Pioneering methods to design and conduct clinical trials that will be more cost-efficient while yielding reliable results.
• Innovative statistical approaches to conduct sample size estimations, control covariates, and assess treatment outcome.
• Using pharmacogenetics and pharmacogenomic techniques to assess genetic factors that may influence the outcome of treatment of a SRD.
• Investigating innovative imaging technologies to assess subjects suitability for specific treatments, as well as treatment progress and outcome (imaging studies must be focused on treatment).
• Developing novel psychotherapeutic techniques to be utilized as a standardized co-adjuvant therapy for subjects participating in medications clinical trials.
• Adapting behavioral therapies that have been shown efficacious and testing them as part of pharmacotherapy clinical trials.
• Novel strategies for the treatment of multiple comorbid SRDs. For example, illicit drug use plus alcohol and tobacco or comorbid opiate and cocaine ( speedball ) dependence.
• Innovative approaches of the treatment of SRDs with other medical and psychiatric comorbidities including, but not exclusively, hepatitis C, HIV infection, anxiety-related disorders, mood disorders, personality disorders, etc.
• Evaluation of biopsychosocial factors that may affect the treatment outcome of SRDs.

Overall Characteristics of all NIDA Centers

NIDA provides support for research center grants to foster an innovative, synergistic and thematically coherent approach to drug abuse and addiction research and to enable studies that would not occur without the climate, facilities and research resources that a research center can uniquely provide. NIDA encourages the application of multiple scientific perspectives and approaches to the problem of addiction. NIDA's research centers program is intended to support the highest quality, multidisciplinary programs of innovative research.

NIDA centers are expected to have three essential and defining qualities. First, they are expected to be scientifically innovative. Centers are expected to provide the next generation of ideas and approaches. Incremental work, though valuable, should not be the focus of Center activities. Rather, new and creative directions are required, and it is expected that a Center will transform knowledge in the sciences it is studying. Second, each NIDA center is expected to be thematically coherent and is expected to demonstrate the highest caliber of multidisciplinary scientific work. The uniqueness of each center emerges from the confluence of thematic integration, and multidisciplinary involvement. The third quality of a NIDA center is synergy. Taken as a whole, a NIDA center is expected to enable a level of achievement that exceeds that expected on the basis of "the sum of its parts." Research supported at a NIDA research center is expected to reflect an inter-dependence of the individual research projects that would not occur simply from the collection of the individual components. Center support should be essential to the achievement of the proposed work.

In addition, NIDA research centers are expected to serve as national research resources in the drug abuse research field. They are expected to attract established and promising investigators into drug abuse research. The P50 center applications are expected to provide opportunities for research training, career development, and mentoring, as well as for effective dissemination of research findings.

Through the Centers program, NIDA seeks to encourage outstanding scientists to bring a full range of expertise, approaches, technologies, and creativity to the study of problems related to drug abuse and addiction. Investigative efforts are expected to be broadly based and to encompass a variety of areas, including biological, biomedical, social, behavioral, and/or clinical sciences as well as dissemination sciences to address critical research issues.

Program Objectives of a P50 Center

A P50 provides support for a broadly based, multidisciplinary, innovative research program consisting of related research endeavors and an associated administrative core infrastructure to ensure their effective and synergistic functioning. The activities included in the supported research are expected to be innovative, thematically integrated, multidisciplinary, and synergistic. It is important that the research supported not be simply a collection of independent research projects that are only loosely related. Each individual research component is expected to be systematically related both to some other components and to the administrative core infrastructure. Training and mentoring to enhance junior researchers' or other researchers' skills should be conducted in the context of the research, but funds may not be used for training stipends or training not required to conduct the research.

Elements of NIDA Centers

Essential Organizational and Administrative Characteristics of a NIDA Center

The application needs to justify the configuration and numbers of components proposed and to demonstrate that the proposed center infrastructure would facilitate effectively the achievement of the desired level of integration and synergy. The center mechanism is not appropriate to support a set of complex unitary investigations that would be best supported as individual R01s.

All NIDA centers are expected to clearly demonstrate the occurrence of innovative, rigorous, thematically focused, and productive research that emerges from interdependent components of the research program and that would not emerge from the mere collection of those individual components. Applicants should explicitly discuss the integration of work in the center in the introductory section of the application. Further, it is expected to be demonstrated that the use of the research center mechanism is essential to accomplishing the scientific aims set forth in the application. In addition to narrative, evidence of components' interdependency should be summarized in a table. Organizational structure should be summarized in a diagram.

Three characteristics are necessary for meeting this set of requirements:

1) Innovation -- There must be evidence of scientific innovation. Centers must be at the cutting edge of the science. Centers are expected to provide the next generation of ideas and approaches. Incremental work, though valuable, should not be the focus of Center activities. Rather, new and creative directions are required, and it is expected that a Center will transform knowledge in the sciences it is studying.

2) Thematic integration and multidisciplinary involvement -- There must be an overarching theme that integrates and focuses the center. Further, there must be an essential relationship of each component part to the overall theme of the center and to the other components. Interdependency and integration of the projects should be clearly evident, so that the center does not appear to be a collection of independent research projects. These linkages may be conceptual, spatial, and/or temporal. The type of integration proposed may be different for different genres of science. Some types may emphasize conceptual integration and focus, while others may emphasize sharing of data, instruments, and other resources. Linkages should encourage cross-fertilization of ideas and interactions among investigators that are relevant to the theme. There must be multidisciplinary involvement. That is, there must be research activity across a variety of disciplines or sub-disciplines such that multiple scientific perspectives and approaches are brought to bear on an area or question. There must be evidence that significant multidisciplinary collaborations will occur and contribute to thematic integration as described above.

Interdependency of the scientific projects may allow for a variety of arrangements including, for example, sharing a common subject pool managed through the administrative core which the center’s other components draw from or, for example, the administrative core may provide a common imaging protocol to allow for comparability of data across research projects.

3) Synergy -- Synergy is evidenced by creative thinking, a novel approach, innovations, and highly significant findings. The degree of coordination, interaction, and collaboration should foster original and creative contributions to scientific understanding over and above that which would be obtained if each component existed independently. Synergy refers to the intense interaction among participating components that results in greater depth, breadth, quality of research and productivity. The intellectual interdependency and linkage among the components and the administrative core must result in levels of productivity, quality, and progress that will exceed those expected from combining the individual components in an additive fashion. The center must demonstrate that the whole is greater than the sum of its parts.

In addition, NIDA P50 research centers are expected to serve as national research resources in the drug abuse research field. They are expected to attract established and promising investigators into drug abuse research. The center applications are expected to provide opportunities for research training, career development, and mentoring, as well as for effective dissemination of research findings.

Research Activities

NIDA's centers should support research activities of the highest and most innovative caliber. Research should be consistent with the aims, goals and intents of the FOA. Each separate project should bear an essential relationship to the integrating theme and efficiently use and contribute to center resources. Centers should enable highly innovative and important studies, whether they are developmental activities and pilot projects or more mature, complex investigations. The center should also support the education, training, and mentoring of new investigators, who should be given meaningful roles to play in the center projects. Further, there should be evidence that the presence of a center structure is essential for the accomplishment of the research activities; that the support of the administrative core activities enables the more efficient implementation of associated research; and that this research is innovative and of the highest caliber, as well as consistent with the overall purposes of the NIDA Centers program.

The NIH policies regarding human subjects protection, data safety and monitoring, and inclusion of women, minorities and children must be followed for research proposed involving human subjects. Data Safety and Monitoring plans must be included for all clinical trials, and Data and Safety Monitoring Board plans must be included for phase I, II and III pharmaceutical trials, and stage 1, 2 and 3 behavioral studies, multi-site clinical trials, and prevention health services and other interventions, when appropriate or required. (See Section VIII Required Federal Citations for more information; and NIDA Guidelines for Data and Safety Monitoring plans and Data and Safety Monitoring Board plans at http://www.nida.nih.gov/Funding/DSMBSOP.html and http://www.nida.nih.gov/Funding/GuideDSMB.html, respectively).

Education Activities

As part of serving as a national resource, a NIDA P50 center is expected to provide educational and outreach activities to drug abuse research communities, educational organizations, the general public, and policy makers. Training activities are also expected to recruit and nurture future generations of scientists to engage in drug abuse and addiction research. The center is strongly encouraged to provide programs to develop careers of researchers of ethnic minorities in drug addiction research and to develop programs to eliminate health disparities.

Data, Findings, & Resource Sharing

NIDA's P50 research centers are expected to collect unique and important data, to develop innovative research assessments and methodologies, and to make critical research discoveries which lead their research fields to the next generation of ideas and approaches. These NIDA centers are supported both for their expected crucial scientific accomplishments and for their role as vital resources to the research community. In order to maximize the impact of their work, they are expected to make their data, their methodologies and their findings available in a timely manner to other researchers and those who have a legitimate purpose for the access. In most instances, the data sharing will extend beyond that of one's own center to the research community. This sharing can be accomplished in many ways, including posting findings in the center's website or using archival services. Data sharing plans must be provided (See Section VII Required Federal Citations and http://grants.nih.gov/grants/policy/data_sharing/ for more information.) A plan for development and dissemination of assessments and methodologies and a general publication plan are also expected. The extent to which a NIDA center is a resource to the field by developing and sharing data, methodologies and findings is a major factor in the potential value of a center and is therefore an important criterion in the evaluation and funding of a center application.

Research Environment and Facilities

Each center is expected to provide an environment that promotes the conduct of the highest quality, state-of-the-art research, innovation, and leadership in its areas of investigation. Applicants are expected to demonstrate that the center is, or would serve as, a significant national scientific research resource soon after its establishment. For resubmissions, the applicant is expected to demonstrate how the Center continues to serve as a national resource and its success in doing so.

There must be appropriate and adequate facilities dedicated to the conduct of administrative, shared resource, and research activities. While all members of the center need not be located physically in facilities controlled exclusively by the center, there must be a clearly identifiable physical location for the center which insures adequate administrative oversight for the center and the associated administrative core providing shared resources.

Center Director (Program Director/Principal Investigator (PD/PI))

Each center is expected to have at least one scientifically and administratively qualified center director with responsibility for the scientific, administrative, budgetary, and operational aspects of the center. The center director(s) should be a productive, senior (as documented by publications, patents, honors, and similar indices of stature) and outstanding researcher(s). The center director is responsible for overall coordination and for the development of the center. An individual cannot serve as director of more than one NIDA research center grant. In addition, it is expected that the center director will make a substantial commitment of time and effort to the center. Although the average center director will commit more time to the center and associated activities than the minimum, it is expected that the center director will commit at least 20 percent effort to center administration including the administrative core and 15 percent effort to any other research component directly supported by the center grant.

Multiple center directors are allowed; however, very strong justification for the need of such arrangement is expected to be provided. Also, a Leadership Plan is expected to be provided (see Section III/1B).

Scientific Project Director

Each project is expected to have a scientifically and administratively qualified investigator with responsibility for the scientific, administrative, budgetary, and operational aspects of the project and for coordination with the Center Director and other project directors. The project directors should be productive, outstanding researchers and leaders of the field. The project director is responsible for overall coordination. It is expected that the project director will make a substantial commitment of time and effort to the center, at least 20% percent effort to research-related activities directly supported by the center grant.

Center Investigators

A cadre of experienced, independent and productive investigators should be present with active collaborations in place or planned. These investigators should evidence productivity, stature and leadership, or a potentially strong leadership role, in their respective fields. A broad range of expertise relevant to the center's goals should be present. Investigative efforts may encompass researchers with primary appointments at the applicant institution as well as at other collaborating sites. Investigators are expected to commit to data sharing and ongoing communications with other investigators in the center.

Administrative and Organizational Structure

The center is expected to have appropriate and effective administrative and organizational capabilities to conduct multidisciplinary research, to foster synergy, and to plan and evaluate center activities. There should be clear and convincing evidence of the applicant institution's commitment to the center. Administrative and organizational arrangements should promote joint planning and evaluation activities as well as collaborations and interactions within, between and among programmatic elements of the center. This should include: (a) an overall programmatic structure that effectively promotes scientific interactions, provides for internal quality control of research, publications, and generation of future grant applications, and also takes maximum advantage of the center's drug abuse research capability (the description of these attributes is particularly important when there are multiple participating institutions in the center); (b) an administrative organization that has clear lines of authority, is managed efficiently and cost effectively, and enables effective use and leverage of resources; (c) the use of a standing outside advisory structure that is charged to provide appropriate and objective advice and evaluation, as needed, to the center director; (d) internal advisory, decision-making, and priority setting processes appropriately charged to conduct the activities of the center; and (e) appropriate criteria and processes for determining and sustaining individual participation in the center based on productivity, research direction, and overall contribution. Administrative support might also include plans for recruitment, training, and supervision of staff. The center should have an administrative core that provides general administration, coordination, and oversight of the center activities.

Allowable Budgetary Items and Supportable Activities

Allowable costs in NIH grants are governed by rules set forth in the Public Health Service Grants Policy Statement and the NIH Guide for Grants and Contracts, unless otherwise stated on the Notice of Grant Award. Under these rules, the center director may exercise flexibility to meet unexpected center requirements by re-budgeting or requesting approval to re-budget among budget categories within the total direct cost budget of the center (as shown on the Notice of Grant Award). In developing the budget for administrative core center activities, applicants should take into account funds currently available through existing collaborating grants and explain how these funds might be reconfigured to maximize efficient resource utilization. The center is intended to provide reasonable support for activities clearly related to the specialized research needs of the center, as noted below:

Center Administration

Salaries and support may be provided for a limited number of administrative and clerical personnel. However, salary and support for central administrative personnel, usually paid from institutional overhead charges, such as budget officers, grants assistants, and building personnel, are not allowable.

Administrative support services, including supplies, duplicating equipment, telephone, or maintenance contracts for equipment, when not covered by institutional overhead charges, are permitted.

Salary and support for administrative activities such as public relations, fund-raising, or educational services unrelated to the research are not allowable.

Shared Resources and Services

Shared resources and services intended to provide access to technology that enhances the research productivity of the center and provides foci for scientific interaction and consultation, as well as access to services that facilitate the research and strengthen the administrative and organizational cohesion of the center may be requested.

Costs associated with sharing data and methodologies with the scientific community and training colleagues in the use of such methodologies may also be requested.

Planning and Assessment of Progress

Costs for the use of ad hoc scientific and technical consultants when appropriate and for the conduct of seminar series designed to promote interdisciplinary interaction, education, and center cohesiveness may be requested.

Costs of center planning and evaluation, including the costs of an external advisory committee, may also be requested.

Travel

Travel of the center director and other investigators to scientific meetings justified as essential to the conduct of research under the center may be supported. Applicants should include an estimated cost of travel to the annual NIDA P50 meeting.

Travel of technical staff for training justified as essential to enhancing the quality of the research projects may be supported.

HIV/AIDS Counseling and Testing Policy for the National Institute on Drug Abuse: In light of recent significant advances in rapid testing for HIV and in effective treatments for HIV, NIDA has revised its 2001 policy on HIV counseling and testing. NIDA-funded researchers are strongly encouraged to provide and/or refer research subjects to HIV risk reduction education and education about the benefits of HIV treatment, counseling and testing, referral to treatment, and other appropriate interventions to prevent acquisition and transmission of HIV. This policy applies to all NIDA funded research conducted domestically or internationally. For more information see http://grants.nih.gov/grants/guide/notice-files/NOT-DA-07-013.html.

National Advisory Council on Drug Abuse Recommended Guidelines for the Administration of Drugs to Human Subjects: The National Advisory Council on Drug Abuse (NACDA) recognizes the importance of research involving the administration of drugs with abuse potential, and dependence or addiction liability, to human subjects. 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 Web site at http://www.nida.nih.gov/about/organization/nacda/CouncilStatement.html.

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

Section II. Award Information

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1. Mechanism of Support

This funding opportunity will use the P50 center grant award mechanism(s). The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses Just-in-Time information concepts. It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html).

2. Funds Available

• The National Institute on Drug Abuse intends to commit approximately $7,500,000 to fund 5-7 new and/or competing continuation grants in response to this FOA.
• An applicant may request a project period of up to five years and a budget for direct costs up to $1,000,000 per year.
• Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds.

Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information

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1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education
• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Small Businesses
• For-Profit Organizations (Other than Small Businesses)
• State Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribally Designated Organizations
• County Governments
• City or Township Governments
• Special District Governments
• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• U.S. Territory or Possession
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Regional Organizations
• Other(s):
  • Eligible Agencies of the Federal Government
  • Faith-based or Community-based Organizations.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her 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.

More than one principal investigator may be designated on the application as center director. Multiple PDs/PIs cannot be proposed for any center project. The multiple PD/PI option applies only to the center as a whole. All PDs/PIs must be registered in the NIH electronic Research Administration (eRA) Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations, and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. The NIH review criteria for approach, investigators, and environment have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a grant share the authority and responsibility for leading and directing the program, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

This program does not require cost sharing as defined in the current NIH Grants Policy Statement.

3. Other-Special Eligibility Criteria

Applicants are not permitted to submit a resubmission application in response to this FOA.

Renewal applications will be permitted for this FOA. Renewal applications should demonstrate appreciable progress during the previously funded grant period.

Foreign sites may not apply to this FOA, nor can they constitute a part of a domestic Center application.

It is expected that the MDCE Director(s) possess(es) recognized scientific and administrative competence. The Center Director/PI must show a substantial commitment of time and effort (minimum 35%) to the program and exercise leadership in steering the MDCE direction and maintenance of its quality control. When multiple PIs are involved, it will be expected that there will be a minimum percent effort of 20% for each Center Director/PI. Center Directors may not direct more than one NIDA Center. This applies to applications with single or multiple PIs. If a PI is a Center Director on a center with multiple PIs, he/she may not act as a Center Director on an application in response to this FOA.

Management support and shared functions should be accomplished through an Administrative Core. The Administrative Core should provide for central operations, oversight activities, technical support and exercise of leadership for the overall project management, as well as integration, communication, and coordination of the MDCE. As part of the Core, each application should include a plan for protocol registration and entry to ClinicalTrials.gov (http://clinicaltrials.gov/ ) and designation of dedicated staff for data entry to the system.

Each one of the clinical trials conducted using Center funds should be individually registered in ClinicalTrials.gov and obtain an NCT number. This NCT number should be included in the Data and Safety Monitoring Plan as well as in the annual progress report for the grant.

It is expected that the applicant demonstrate that he/she has plans and facilities for career development and mentoring of junior investigators in the area of drug abuse research and treatment.

Pilot Projects

• Applicants may propose and request funding for specific, already conceptualized pilot projects, which may be research and development pilots, feasibility studies, or other pilot work broadly defined as foundation work for further research. These pilot studies will be reviewed by the scientific review group as part of the assessment of scientific and technical merit.
• Pilot projects, along with their corresponding budgets, should be included in the Administrative Core, for the effective management of personnel and budget resources.
• In addition, applicants may request funds for pilot projects that are yet to be conceptualized. These projects should have the potential for developing into, or providing the foundation for, larger projects that could compete for funds on their own. The support of pilot project studies should be of relatively short duration (e.g., 1-2 years), depending upon the nature of the research. Because these projects cannot be reviewed by the scientific review group, applicants must describe and provide a process for within-center scientific review of pilot projects, which must be ultimately approved by the NIDA program officer. In general, the total amount of money allocated to yet-to-be- conceptualized pilot projects should not exceed 15% of the center grant’s total annual direct costs, and exceptions must be strongly justified.
• Whether specifically proposed in the application or developed later under center auspices, pilot projects must comply with applicable NIH policies, and the necessary human and animal welfare assurances must be submitted, as well as a Data and Safety Monitoring plan for each new study involving human subjects.
• For projects not specifically proposed in the application, Center grantees are to provide the NIDA program officer with written notification of the initiation of new pilot projects. The notification should contain a brief description of, and rationale for, the planned pilot project, the amount of pilot funds to be allocated to the project, the proposed length of the project, and a statement that the project will comply with applicable NIH policies and that the necessary assurances have been submitted and obtained. The program officer must also be provided with assurance that the projects have received an appropriate within-center review. New pilot projects may not commence until they have been approved by the program officer. For studies involving clinical trials, pilot projects may not start subject recruitment before the respective Data and Safety Monitoring Plan has been approved by the NIDA project officer.
• The Principal Investigators are expected to report to the NIDA project officer any serious adverse events (SAEs) that occur in any of the clinical trials conducted under the Center. The NIDA/DPMC invites the PIs to take advantage of, and use, the Serious Adverse Event Tracking and Reporting System (SAETRS) web-based application. Data and Safety Monitoring Plans should include a plan for reporting SAEs to the project officer using SAETRS (as well as to the DSMB, IRB, and FDA).
• During the Centers project period, the NIDA plans to convene an annual Centers meeting to be attended by Center Directors who may invite other Center staff at their discretion, and NIDA staff involved with administration of the Center grants. The purpose of the meeting functions both as a reverse site visit to assess Center progress and as an opportunity for the MDCEs to present their findings and discuss future work amongst themselves. It is understood that some information may be proprietary and not to be disclosed outside of the meeting. Applicants should plan travel budgets accordingly.

Section IV. Application and Submission Information

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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: GrantsInfo@nih.gov.

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 in item (box) 2 only of the face page of the application form and the YES box must be checked.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

More than one principal investigator may be designated on the application as center director, although the multiple PD/PI option applies only to the center as a whole. Multiple PDs/PIs cannot be proposed in the capacity of scientific director for any project. When multiple PD/PIs are proposed, use the Face Page-Continued page to provide items 3a 3h for all PD/PIs. NIH requires one PD/PI be designated as the contact PD/PI for all communications between the PD/PIs and the agency. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PD/PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PD/PI may be changed during the project period. The contact PD/PI should be listed in block 3 of Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in the header of each application page, use the name of the Contact PD/PI, et. al. The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.

All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles such as SO or IAR will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled Multiple PD/PI Leadership Plan must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

Additional information is available in the PHS 398 grant application instructions.

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
Letters of Intent Receipt Date: November 19, 2008
Application Receipt Date: December 19, 2008
Peer Review Date(s): February/March 2009
Council Review Date: May 2009
Earliest Anticipated Start Date: July 2009

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 in Section IV.3.A.

The letter of intent should be sent to:

Director DA 09-002
Office of Extramural Affairs
National Institute on Drug Abuse/NIH/DHHS
6101 Executive Blvd, Suite 220, MSC 8401
Bethesda, MD 20892-8401
Rockville, MD 20852 (for express/courier service)
Telephone: (301)443-2755
FAX: (301)443-0538
Email: tlevitin@mail.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the forms 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:

Director
Office of Extramural Affairs, NIDA
6101 Executive Blvd, Room 220, MSC 8401
Bethesda, Maryland 20892-8401
Telephone: (301) 443-2755
FAX: (301) 443-0538
Email: tlevitin@mail.nih.gov

3.C. Application Processing

Applications must be received on or before the application receipt date) described above (Section IV.3.A.). If an application is received after that date, the application may be delayed in the review process or not reviewed. Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute Incomplete and/or 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 NIH Grants Policy Statement.

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 renewal award if such costs: 1) are necessary to conduct the project, and 2) 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 renewal 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 and Information

Research Plan Page Limitations

Applications should be organized according to the following scheme: face page, abstract page with key personnel, table of contents, summary budget pages for the entire MDCE followed by budget pages for the Core and projects, Biosketches for all key personnel affliliated with the entire center, Resources and other documentation pertaining to the entire center, such as letters of support). This should be followed by a section titled Center Characteristics of no more than 15 pages that addresses the ways in which the application meets the criteria of the FOA and of a NIDA Center (page 7, Special Considerations Overall Characteristics of All NIDA Centers ). Then the Core/projects follow with each containing its Abstract, Resources unique to the Core/project, if any, and its Research Plan (i.e., Specific Aims, Background and Significance, Preliminary Studies/Progress Report, and Research Design and Methods). Research plans are not to exceed 15 pages to describe the administrative layout for the Administrative Core and 20 pages for the projects. If pilot studies are proposed, these should be described within the Administrative Core section. Additional pages to describe pilot studies (3 pages maximum per pilot study; not to exceed 15 pages total) will not count towards the 15 page limit imposed on the description of the administrative layout of the Administrative Core.

Renewals

For renewals (formerly competing continuations, Type 2), a progress report, not to exceed 10 pages, of the previously funded research must be provided, following the Resources section and before the Center Characteristics section. There should be evidence that the previously funded center enables the more efficient implementation of research projects and that this research is innovative and of the highest caliber, as well as consistent with the overall purposes of the NIDA Centers program and the requirements of this FOA. In addition, applicants should demonstrate the research environment’s conduciveness to productivity by identifying the originally approved specific aims, the progress made on each specific aim, and relevant publications produced in the previous funding period. It is especially important that renewal applications (1) identify innovative work accomplished by the Center during the current funding period and (2) proposed innovative work for the new funding period.

In the text of the application, there must be a section titled Progress Report which includes a detailed summary of the previous application’s specific aims and highlights the importance of the findings. The innovation of the work/results must be highlighted. The application should provide the initial Specific Aims, describe and justify any changes in the Specific Aims and present major findings, describing clearly the importance of these findings to the advances in the field, and include the complete references to appropriate publications and manuscripts accepted for publication. The application should also address any significant organizational changes, and provide summaries of training activities for junior investigators as well as results of education and dissemination activities. The application must also provide a summary of recruitment, retention, and safety issues, for each clinical trial or study conducted.

Appendix Materials

All paper PHS 398 applications submitted must provide appendix material on CDs only. Include five identical CDs in the same package with the application. (See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html.)

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition. For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

Section V. Application Review Information

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1. Criteria (Update: Enhanced review criteria have been issued for the evaluation of research applications received for potential FY2010 funding and thereafter - see NOT-OD-09-025).

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

2. Review and Selection Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIDA and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

• Undergo a selection process in which only those applications deemed to have the highest scientific and technical merit, generally the top half of applications under review, 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 following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by peer review
• Availability of funds
• Relevance of the proposed project to program priorities
• The qualifications and experience of the center director and other key personnel;
• The extent to which the various components of the proposed program would be coordinated into one multi-disciplinary effort within the center;
• The extent to which the center's activities would be coordinated with similar efforts by other organizations;
• The administrative and managerial capability of the applicant,
• Past performance of Centers submitting renewal applications

The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In their written comments, reviewers will be asked to discuss the following aspects of the scientific project component 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 considered in assessing merit. Of particular importance will be the innovation of the project and the likelihood that the results would have a major impact. Furthermore, successful centers are expected to show outstanding merit on all criteria.

Review Criteria for Overall Center

Significance: Does the overarching theme of the center address an important problem in drug abuse and addiction? If the aims of the center are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts or methods that drive this field? How well does the application match the aims, intents and goals of the FOA?

Approach: How well integrated are the various center components (including components not directly supported under a P50, but which utilize administrative core functions) in relation to the overarching theme of the center? Does each of these sub-components help focus the center while still contributing to an essential relationship between component and center? Are the various components clearly identified and well defined? Are the interdependency and linkages among components clearly demonstrated for at least a significant nucleus of components?

Evidence of synergy among components. What will determine the quality of provisions for the sharing of resources between various components? Is there evidence of procedures for formal and informal planning among components? Are there plans for developmental or pilot work that reflects a depth and breadth of expertise and experience among components that are not normally found in an individual research project grant?

Evidence that multidisciplinary or cross disciplinary research will be emphasized. What emphasis has been placed on the involvement of different scientific disciplines or sub-disciplines across the center's activities? What evidence is there that there will be substantial interaction among various scientists from different disciplines and/or sub-disciplines?

Progress (Applicable to all competing renewals). During the previous project period, did the Center demonstrate innovation? Does the application describe the impact of work completed during the previous/current funding period? Does the application provide evidence of substantial progress in reaching stated goals? (This includes, but is not limited to, records of publications, quality and quantity of publications, dissemination, patents, awards, training activities, placement record of trainees.)

Administrative and Organizational Structure: Does the applicantion clearly outline and/or diagram the center’s administrative/organizational structure? Is this administrative/organizational structure conducive to the center s approach to synergistic research and integrative planning? Does the administrative/organizational structure provide for long-range planning and evaluation of the center’s overarching activities? Does the administrative/organizational structure effectively promote productive scientific interactions between the various components and/or sub-components? Does the administrative/organizational structure take maximum advantage of the applicant institution's drug-abuse research capacity? Does the administrative/organizational structure maximize the quality and extent of data analytical capacities, database facilities, component research coordination, and the sharing of other data-collection resources? Does the administrative/organizational structure maximize the quality of provisions for shared laboratory resources (e.g., clinical facilities and equipment)? Does the administrative/organizational structure define who will be primarily responsible for internal quality control of research protocols, submitting/publishing scientific publications, and composing/re-submitting additional and/or subsequent grant applications? Does the administrative/organizational structure lay out an organizational structure with clear lines of authority that allow for efficient and cost-effective management and allocation of funds, as well as leverage of resources to enable additional or future work? Is there evidence that administrative core components contribute toward an overall cost-effectiveness and quality control in resource utilization? Does the administrative/organizational structure provide for an outside advisory structure that will offer objective advice and evaluation of research practices? Does the administrative/organizational structure appropriately and fully describe an internal process that defines priority setting and decision making amongst PIs at various components to sustain the center? Does the administrative/organizational structure specify appropriate criteria and processes for determining and sustaining individual participation in the center based upon productivity, research direction, and overall contribution? Does the administrative/organizational structure provide clear plans for the recruitment, training, and supervision of staff?

Applicant institution's substantial commitment to the center. . Is there clear and convincing evidence (e.g., letters of support, space and allocation of resources) that the applicant’s institution is substantially committed to the applicant’s role as a program center? Does the applicant s institution demonstrate an appreciation of the center’s overarching goals and its significant role in public health, especially within the drug abuse and addiction research field?

Education Activities: Does the center outline an effective approach to attract and train high-quality junior investigators and students who demonstrate the potential for substantial future contributions and independent research careers?

National resource: Does the center describe a clear plan in which it will disseminate its data and research findings to the national research community? Does the center outline an effective means of contributing to educational and outreach activities within national drug-abuse research communities, organizations, the general public, and/or with national policy makers?

Innovation: Do the proposed research projects exhibit a high probability of moving the drug-abuse field to a new and higher level of accomplishment? Do the proposed research projects for each component within the center contribute to the overall innovation in approach, techniques, problem solving, conceptualization and/or other novel research areas? If a competing renewal, does the applicant demonstrate how work during the previous/current funding period at each of the center components has been innovative and creative for the center as a whole?

Investigators: Qualifications of the Center Director(s):: Is there evidence that the Center Director has the ability to lead an integrative scientific program (including a program with training components), as noted by his/her scientific achievements, productivity, stature in his/her relevant scientific field, and planned activities? Is there evidence that the Center Director has the ability to lead the various administrative and operational aspects of the center, as noted by his/her managerial skills, scientific achievements, and planned activities? Does the Center Director have the networking skills and collaborative alliances to develop and maintain a role for the center as a national resource? Does the Center Director commit an adequate amount of time and effort toward the research and administration of the center?

Multiple PD/PI leadership plan ( if applicable). Is the leadership plan clearly set forth? Does the leadership plan adequately describe the administrative, operational, and decision-making structure? Do the structure and governance of the leadership plan complement and enhance the overall knowledge, skills and experience of the individual PD/PIs?

Qualifications of component directors: Is evidence provided that each of the component directors possesses adequate leadership ability? Has each of the component directors demonstrated sufficient scientific productivity and honors and recognition within his/her scientific research field? Do the component directors have any previous intra- and/or inter-institutional collaborative experiences that have been conducted in manner to complement the breadth of expertise represented and/or the multidisciplinary quality of investigations among participating PIs/sites?

Environment: Is there a clearly identifiable physical location for the program center? Does the environment at the program center and each of those affiliated components have appropriate and adequate facilities to accomplish the proposed research aims? Does the collective environment have shared resources which would assure that necessary research functions can occur and, perhaps, even be completed with greater overall quality? Is there any evidence that the collective facilities of the center and its components have the potential to be a national scientific research resource? Are there plans for the development and maintenance of an environment that promotes the conduct of the highest quality of research, innovation, leadership and training (see also administrative and organizational structure)? If a competing renewal, has the center demonstrated collective productivity and innovation?

Review Criteria for Individual Projects

Significance: Does this study address an important problem in the drug abuse and addiction field? If the aims of the project 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? Is the project well integrated into the overarching theme of the center?

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

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 novel concepts, approaches, methodologies, tools, or technologies for this area??

Investigators: Are the PD/PI(s) and other key personnel 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? Is the principal investigator considered a leader in the field or has the principal investigator demonstrated potential leadership quality? How does the principal investigator contribute to the research team for this project and for the center as a whole?

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

Review Criteria for the Administrative Core

Significance: Does the Core appear to be satisfactorily integrated with, and central to, other Center components?

Approach: Is the management and administrative plan appropriate? Are the line of authority and decision making process clearly specified? Is oversight provided? If pilot studies are proposed, what is the purpose of the pilot studies? Is there a selection process in place? Is the selection by open competition or by nomination? Are projects investigator-initiated or determined in some other way? How well are the pilot projects related to the theme of the center? Will the projects enhance the training of the junior investigators? What is the likelihood that the research will contribute to the development of multidisciplinary programs or more mature independent research endeavors?

Innovation: Will the connectedness, workload planning, and priority setting for the projects to be served within the Administrative Core help push the drug abuse field to a new, higher level? Is there evidence of innovative, state-of-the-art analytical capabilities within the Administrative Core? Are there adequate provisions for the sharing of findings, database development, and potential state-of-the-art analytical capacities within the Administrative Core?

Investigators: Do the proposed directors(s) exhibit the managerial capabilities and scientific credentials to lead the Administrative Core? Do the proposed director(s) plan an appropriate level of the effort?

Environment: Are there appropriate and adequate facilities for the administrative, research, and shared resources, including a clearly identifiable physical location for the center, that would assure all necessary functions can occur within the Administrative Core? Are the facilities within the Administrative Core indicative of a research center that is, or has the potential to be, a national scientific research resource?

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the rating:

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 on Human Subjects in the PHS 398 instructions).

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 on Human Subjects in the PHS 398 instructions).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five points described in the Vertebrate Animals section of the Research Plan 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. The priority score should not be affected by the evaluation of the budget.

2.C. Resource Sharing Plan(s)

When relevant, reviewers will be instructed to comment on the reasonableness of the following Resource Sharing Plans, or the rationale for not sharing the following types of resources. However, reviewers will not factor the proposed resource sharing plan(s) into the determination of scientific merit or priority score, unless noted otherwise in the FOA. Program staff within the IC will be responsible for monitoring the resource sharing.

• Data Sharing Plan. [http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm]
• Sharing Model Organisms. [http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html]
• Genome Wide Association Studies (GWAS). [http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html]

3. Anticipated Announcement and Award Dates

Not Applicable

Section VI. Award Administration Information

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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.

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).

3. Reporting

Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

Section VII. Agency Contacts

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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:

Jamie Biswas, Ph.D.
Chief, Medications Research Grants Branch
Division of Pharmacotherapies and Medical Consequences of Drug Abuse
National Institute on Drug Abuse, NIH, DHHS
6001 Executive Boulevard, Room 4123, MSC 9551
Bethesda, MD 20892-9551
Telephone: (301) 443-8096
Fax: (301)443-9649
Email: jbiswas@nida.nih.gov

2. Peer Review Contacts:

Teresa Levitin, Ph.D.
Director, Office of Extramural Affairs
National Institute on Drug Abuse, NIH, DHHS
6101 Executive Boulevard, Suite 220, MSC 8401
Bethesda, MD 20892-8401
Telephone: (301) 443-2755
Fax: (301) 443-0538
Email: tlevitin@mail.nih.gov

3. Financial or Grants Management Contacts:

Deborah Wertz
Grants Management Specialist
Grants Management Branch
National Institute on Drug Abuse
6101 Executive Boulevard
Suite 270 MSC 8403
Bethesda MD 20892-8403
Telephone: (301) 443-6710
FAX : (301) 594-6847
E-mail: dwertz@nida.nih.gov

Section VIII. Other Information

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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.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/

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 Requirement:
In accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html) investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigator’s NIH award. For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

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

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

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. 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 FOA 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. 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.