Part I Overview Information


Department of Health and Human Services

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

Components of Participating Organizations
National Institute of Mental Health (NIMH) (http://www.nimh.nih.gov)
National Institute on Drug Abuse (NIDA) (http://www.nida.nih.gov/)
National Institute on Alcohol Abuse and Alcoholism (NIAAA) (http://www.niaaa.nih.gov/)

Title: National Cooperative Drug Discovery Groups for the Treatment of Mental Disorders, Drug or Alcohol Addiction (U19)
Announcement Type
This is a reissue of PAR-04-009, which was previously released October 16, 2003.

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

Program Announcement (PA) Number: PAR-07-159

Catalog of Federal Domestic Assistance Number(s)
93.242, 93.273, 93.279

Key Dates
Release/Posted Date:  December 14, 2006
Letters of Intent Receipt Date(s): February 22, 2007; August 17, 2007; January 25, 2008; August 18, 2008; January 26, 2009; August 17, 2009 
Application Submission Date(s): March 22, 2007; September 17, 2007; February 25, 2008; September 17, 2008; February 25, 2009; September 17, 2009 
Peer Review Date(s): June/July 2007; November/December 2007; May/June 2008; November/December 2008; May/June 2009; November/December 2009
Council Review Date(s): October 2007, January 2008, October 2008, January 2009, October 2009, January 2010
Earliest Anticipated Start Date(s): November 2007, February 2008, November 2008, February 2009, November 2009, February 2010  
Additional Information To Be Available Date: Not Applicable
Expiration Date: September 18, 2009 - (Now Expired August 14, 2008 per PAR-08-238)

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Table of Contents


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
  1. Research Objectives

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

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

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

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

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

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

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


1. Research Objectives

Purpose

The intent of this solicitation is to invite applications from academic, biotechnology, or pharmaceutical industry investigators interested in participating with the National Institute of Mental Health (NIMH), the National Institute on Drug Abuse (NIDA), or the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in a National Cooperative Drug Discovery Group (NCDDG) Program to accelerate innovative drug discovery, testing of novel compounds in preclinical models, and the development of pharmacologic tools for basic and clinical research in mental disorders, drug or addiction, and the development and validation of models for evaluating novel therapeutics for mental disorders.  NIMH, NIDA, and NIAAA are interested in jointly advancing the discovery of new ligands for drug targets as tools to advance biological research on the function of genes, cells, and biochemical pathways implicated in the etiology and pathophysiology of mental disorders, drug or alcohol addiction, and as potential new therapeutics.

The goal of the NCDDG Program is to establish partnerships between NIH, academia, and industry to advance the development and testing of new, rationally based (mechanism of action-based) candidate medications and research tools to advance the treatment of mental disorders, and drug or alcohol addiction.

Academic and/or pharmaceutical industry components of each NCDDG should contribute unique scientific expertise towards the common goal of translating basic science findings into innovative pharmacologic treatments for mental disorders, or drug or alcohol addiction.  Each partnership or group must consist of a multi-disciplinary team of scientists with appropriate expertise to address the development and evaluation of novel ligands, and the development of testing models where required.  Scientists from both academia and pharmaceutical industry are encouraged to participate within an NCDDG.  Scientists from foreign institutions and NIH Intramural laboratories may participate in some aspects, as noted in other sections of this funding opportunity.

The NCDDG Program is most appropriate for applications that include collaborations, research projects, in kind support, or core components from academia and the private sector (e.g., pharmaceutical, chemical, toxicology, or biotechnological companies), although a private sector partner is not required.  It is anticipated that the interaction of academic and non-profit research institutions with industry and NIH via the NCDDG model will:  1) accelerate the discovery of new therapeutics for mental disorders, and drug or alcohol addiction; 2) increase the availability of pharmacologic research tools (including imaging agents) for basic and clinical research; and 3) facilitate the development and validation of models to evaluate novel therapeutics for mental disorders.

The goal of the NCDDG program is not to duplicate or compete with the private sector but to complement and accelerate the development of research tools for new molecular targets implicated in mental disorders, or drug or alcohol addiction, and of effective compounds for the prevention and treatment of psychiatric and addictive disorders, as well as core features of these illnesses, especially in areas of unmet medical need.

Background

Significant advances in neuroscience, genetics, and basic behavioral science, together with technological developments, have provided a rich knowledge base for understanding pathophysiology, identifying new molecular targets for drug discovery, and developing rational pharmacotherapies for the treatment of psychiatric and substance abuse disorders.  With the wealth of potential new drug targets, the opportunity exists to accelerate the process of target validation and medication discovery to make quantum leaps toward novel and effective treatments for mental disorders and drug or alcohol addiction.

NIMH’s objectives and interests for the NCDDG program

NIMH’s objective for the NCDDG program is to establish public-private partnerships to conduct innovative, high impact research focused on the discovery of pharmacological agents targeting novel molecular targets implicated in the pathophysiology of mood and anxiety disorders, schizophrenia, eating disorders, obsessive-compulsive disorder, fragile x, autism, and other mental illnesses. Research projects directed towards ameliorating clinical dimensions of psychopathology embedded in DSM diagnostic entities, but not typically identified as the primary target of current clinical therapeutics, are also encouraged. 

NIMH relevant NCDDG research projects can focus on one or more molecular targets and include two or more of the following projects or components:  1) ligand discovery for therapeutics development and as research tools (e.g. imaging probes) for novel molecular targets implicated in mental illnesses; 2) preclinical testing of novel compounds in disease-based models, 3) development and validation of novel, disease-based genetic models combined with environmental or behavioral manipulations for evaluating therapeutic compounds; 4) initial Good Laboratory Practice (GLP) toxicology, safety pharmacology, and pharmacokinetics to support an Investigational New Drug (IND) application to the Food and Drug Administration (FDA) to begin human clinical testing, and/or 5) limited phase 1 studies. 

Private sources of funding should be identified in the application to support Good Manufacturing Practice (GMP) synthesis, formulation, and/or IND filing costs.  Cost-sharing for IND-directed toxicology and safety studies is encouraged. Additional toxicology and safety studies to support phase II efficacy trials are beyond the scope of this FOA.

Specific go/no go decision-making points and quantitative milestones should be included for assessing progress and success toward the therapeutic development goal; these milestones will be used by program staff in assessing yearly progress and continued funding.

NIDA’s objectives and interests for the NCDDG program

NIDA's interests are in the discovery of ligands that constitute important research tools and/or medication candidates to advance the development of pharmacotherapies for drug addiction treatment. Over the past decade or so, there have been major advances in our understanding of the protein targets, neural circuitry, and behavioral phenomena associated with addiction, and in the effects of drugs of abuse on CNS processes associated with addictive behavior, such as synaptic plasticity.  The initial targets for most drugs of abuse are known and have been shown to be predominantly either G-protein coupled receptors, such as the dopamine receptor, an indirect site of action for cocaine and amphetamine, or ligand gated ion channels, such as the nicotinic cholinergic receptors (nAChRs), a target for nicotine.  Drug addiction also involves activation of intracellular signaling proteins that can affect the response to drugs of abuse, and there is clear evidence for the involvement of numerous, specific neurotransmitter systems in addiction.  Genetic polymorphisms are likely to lead to variation in the biological activity in many of these protein targets, which may be relevant to individual variability in response to drugs of abuse and, ultimately, to vulnerability to addiction. Given that research has discovered some of the mechanisms through which addictive drugs act in the CNS, numerous potentially viable targets for medications are known and, for the most part, well characterized.  Hence the opportunity exists for the development of new ligands for target validation studies and potentially for development as pharmacotherapies.

From NIDA’s perspective, the NCDDG is a ligand discovery and translational initiative in which the objective is the development of molecules with a particular profile of action as prototypes for medications to treat addiction or as tools to advance research in the treatment development domain.  A number of cellular and animal models are currently available for ligand discovery efforts relevant to drug addiction treatment research.  It is therefore expected that responsive groups will include a program to evaluate the efficacy of novel ligands in appropriate models.  Components of NIDA-relevant NCDDG research projects could include, but are not limited to: (1) assessment of the behavioral profile of novel ligands in tests of reinforcement, relapse and withdrawal; (2) tests of the ability of novel ligands to modulate cellular processes of plasticity in reward-relevant regions of the brain; (3) assessment of ligand efficacy on G-protein coupled receptors and ligand gated ion channel activation; and 4) receptor activation effects on down-stream intracellular systems or in modulating the release of addiction-relevant neurotransmitters.  Projects that propose integrating two or more of these approaches also are encouraged. 

Two targets, the mu-opiate receptor and the dopamine transporter, have been extensively pursued in medication discovery efforts related to opiate and cocaine addiction, respectively.  Given the clinical availability of mu-opiate agonists, partial agonists and antagonists and the large number of NIDA-supported grants already focusing on the dopamine transporter, NIDA is not interested in supporting NCDDG projects with a focus on these two targets.  Applicants are encouraged to focus on the discovery of truly novel ligands through the pursuit of targets such as orexin (hypocretin) and nicotinic acetylcholine receptor subtypes.  A more extensive list of targets for consideration can be found below.   

NIAAA’s objectives and interests for the NCDDG program

NIAAA’s interests for the NCDDG program are in the discovery of novel ligands that may lead to the development of medications for the treatment of alcohol dependence and addiction, and ligands that may be used as research tools to understand the biological processes that contribute to compulsive drinking. The focus of proposed research projects should follow that described above by NIMH, but should be relevant to the mission of NIAAA.

Three compounds are currently approved for clinical use in treating alcohol dependence and addiction. Their mechanisms of action differ, and each appears most useful in treating a certain behavioral aspect that contributes to problem alcohol consumption. Disulfiram (Antabuse) is an inhibitor of aldehyde dehydrogenase. Taking disulfiram leads to a systemic build up of acetaldehyde when alcohol is ingested. This is experienced as an unpleasant intoxication and creates an aversion to consuming alcohol. Naltrexone is an opiate receptor antagonist. By attenuating opioid receptor activity, naltrexone reduces dopaminergic transmission in the mesolimbic reward pathway following alcohol consumption. As such, naltrexone prevents relapse to heavy drinking by reducing the rewarding effects of alcohol consumption. The mechanism of action of acamprosate is inconclusive, but it is thought that acamprosate attenuates the enhanced glutamatergic transmission observed following withdrawal from chronic alcohol consumption. Acamprosate appears best at reducing craving and maintaining abstinence. Each medication has been found to be highly effective in some patients, yet other patients fail to respond to them. Thus, there is a need for the development of new medications that interact at additional targets, and that treat additional behavioral facets of alcoholism.

Medications development for alcoholism is not a simple process in light of alcohol’s multiple biological effects, and the many physical and behavioral alterations that occur following regular alcohol use and abuse. Consider that there are multiple components of alcohol addiction, including: 1) a hedonic, rewarding response to alcohol mediated through the brain’s reward circuitry, 2) learning and memory processing within the hippocampus, 3) reduced executive control involving frontal cortical regions, and 4) physiological alterations such as activated stress pathways resulting from altered hypothalamic activity. Current pharmaceutical strategies for treating alcohol use disorders are broadly designed towards developing agents that: a) modify alcohol intoxication, reducing the pleasurable effects of alcohol or increasing the aversive effects, b) reduce craving or the urge to drink, c) reduce the signs and symptoms of acute and protracted withdrawal syndromes, and d) treat co-morbid psychiatric illnesses or reduce psychological distress which contributes to elevated alcohol consumption. Clearly, there can be multiple goals towards drug development in treating alcoholism.

NIAAA sees the NCDDG as an opportunity to identify and develop compounds towards both existing and new molecular targets having the potential to treat alcohol use disorders, or to facilitate and enhance basic and clinical research on identifying the neurobiological and behavioral processes that contribute to the transition from voluntary to compulsive drinking. Aspects of alcohol consumption and alcohol-seeking behaviors are modulated through the actions of neurotransmitter receptors and transporters, ion channels, neuromodulators, hormones, and intracellular signaling networks. Thus, there are a number of potential target sites for which new pharmaceutical agents may be developed, such as effectors of opioid, serotonin, dopamine, glutamate, GABA, cannabinoid, and adenosine receptors, modulators of neuropeptide systems (NPY, CRF), and agents that alter signal transduction pathways (such as protein kinase effectors, protein phosphatase inhibitors, G-protein regulators and calcium signaling disruptors). The identification and pursuit of agents towards novel targets previously un-recognized or understudied for the treatment of alcohol abuse disorders is especially encouraged. Applications that essentially propose to further extend the testing of established or well-studied compounds will be considered unresponsive to this FOA.

Cellular models may be used as initial screening tools to evaluate the molecular properties of candidate compounds. However, it is further expected that the more promising compounds will be tested and evaluated in established animal models of behavioral aspects of alcoholism, such as drinking, dependence, craving and reinstatement models (see Drug Discovery Today: Disease Models 2: 313, 2005). As no single compound is expected to address all of the behavioral aspects and consequences of alcoholism, projects that propose integrating two or more behavioral testing paradigms are especially sought.

Summary

In summary, the NCDDG Program will support broad, innovative, multidisciplinary, multi-project approaches to the discovery of new, rationally based  treatments and research tools for mental disorders, drug or alcohol addiction.  Since the creative talents in the required scientific disciplines are rarely available in a single institution, a multi-institutional, group approach involving academic, nonprofit, commercial, and/or industrial institutions is envisioned.  Academic and pharmaceutical scientists are strongly encouraged to form partnerships that take full advantage of their combined intellectual and material resources for drug discovery, lead optimization, and model development.  Further, the interaction of academic and non-profit research institutions with pharmaceutical industry and NIH is expected to facilitate subsequent development and marketing of new pharmacologic treatments, although these latter activities are not within the scope of this FOA.  Molecular targets for drug discovery, and the sources and types of chemical entities to be investigated, will be selected by the applying group.  Both mechanism of action and disease-oriented approaches are of interest.

Research Scope

The objective of this FOA is to establish NCDDG Groups to conduct innovative, high impact research focused on the discovery and testing of chemical entities for novel molecular targets implicated in the pathophysiology of mental disorders, or drug or alcohol addiction.  The NCDDG serves as a vehicle for pharmaceutical and academic scientists to pool intellectual and material resources for the translation of basic science findings into the conceptualization, discovery, and evaluation of new chemical entities.  Groups are encouraged to select molecular targets for drug discovery based on recent findings in basic and clinical neuroscience, genetics, and proteomics relevant to the understanding of mental disorders and addiction. 

Molecular targets that applicants may wish to consider include, but are not limited to, the following.  Please contact program staff listed in Section VII.1. Agency Contact(s) “Scientific/Research Contacts," to determine program priorities and molecular targets of interest to specific NIH Institutes or refer to the Internet addresses listed above for each of the participating institutes.

Potential ligands of interest to NIMH, NIDA and NIAAA might be identified by their receptor properties (e.g., allosteric modulators, partial agonists, agonists, or antagonists), solubility, pharmacokinetics, oral or CNS bioavailability, or other characteristics to support their use as research tools or candidates for drug development.

The identification of lead compounds and refining them for medication development is an important goal of this initiative.  Generally this can involve classical approaches of medicinal chemistry using structure-activity relationship (SAR) rationales.  The use of chemical libraries, structural biology and computer modeling of molecular targets to screen for compounds with activity at selected targets are also examples of responsive approaches.  If applicants do choose to conduct library screening, they are encouraged to focus on targeted libraries rather than random structural screening.  Screening of existing libraries (e.g. G-protein receptor-focused) that will not require significant synthetic resources is encouraged.  Note that the pharmaceutical industry has reduced its reliance on combinatorial chemistry approaches due to general lack of success.  While NIDA, NIMH and NIAAA will not rule out the use of combinatorial chemistry in NCDDG projects, applicants proposing them should provide appropriate justification that this approach to compound synthesis is desirable. 

Responsive applicants may outline plans for the development and evaluation of cellular, circuit, genetic, or pathophysiology based models for validation of novel targets (preliminary proof-of-concept) for mental disorders, and drug discovery and the identification of compounds as potential candidates for drug development for mental disorders, or for drug or alcohol addiction.  The discovery, development, and testing of new chemical entities as clinical candidates for treating these disorders is a mandatory component of the NCDDG.

It is anticipated that the interaction of academic and non-profit research institutions with NIH and pharmaceutical industry will facilitate timely evaluation and development of preclinical and clinical research tools, models, and novel therapeutics.

Note:  The development of analogs of established or well-studied agents for the treatment of mental disorders, drug or alcohol abuse is not responsive to this FOA.  Cost-sharing for IND-directed toxicology and safety studies is encouraged.  Private sources of funding should be identified in the application to support GMP synthesis, formulation, and/or IND filing costs.  Toxicology and safety studies exceeding 28 days in duration and phase II efficacy trials are beyond the scope of this initiative.  For applicants seeking additional sources of support for preclinical development activities such as toxicology and safety pharmacology assessment, bulk synthesis, GMP manufacturing, or formulation development, the NIH Rapid Access to Interventional Development (NIH-RAID) (http://nihroadmap.nih.gov/raid/) program, part of the NIH Roadmap, offers investigators access to preclinical development resources on a competitive basis.  

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

Section II. Award Information


1. Mechanism of Support

This funding opportunity will use the U19 award mechanism.  As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses the just-in-time concepts. It also uses the non-modular budget format described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). A detailed categorical budget for the "Initial Budget Period" and the "Entire Proposed Period of Support" is to be submitted with the application.

The NIH U19 is the research program cooperative agreement which supports a research program of multiple projects directed toward a specific major objective, basic theme or program goal of discovery of new, rationally based  treatments and research tools for mental disorders, drug or alcohol addiction,, requiring a broadly based, multidisciplinary and often long-term approach.. In the cooperative agreement mechanism, the Principal Investigator retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".

2. Funds Available

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  participating Institutes provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

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

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

2. Cost Sharing or Matching

This program encourages, but does not require, cost sharing with biotechnology, pharmaceutical, or disease foundations for IND-directed toxicology and safety studies as defined in the current NIH Grants Policy Statement.  Private sources of funding should be identified in the application to support GMP synthesis, formulation, and/or IND filing costs.

3. Other-Special Eligibility Criteria

Applicants may submit more than one application, provided they are scientifically distinct.

SPECIAL REQUIREMENTS

A.  The NCDDG Program objectives and goals should be relevant to and compatible with the NIMH, NIDA and/or NIAAA priorities for innovative drug discovery, development of pharmacologic tools for research, and, for NIMH, development and validation of models for mental disorders as specified in this FOA.  Applicants should describe their plans to accommodate the stated NCDDG requirements, criteria, and NIMH, NIDA and/or NIAAA involvement.

B.  A proposed Group can consist of scientific collaborators focused on at least two Research Projects and Scientific and Administrative Core components (U19 mechanism).  It is anticipated that the Groups will include outstanding scientists from diverse scientific disciplines within neuroscience, neuropharmacology, neurobiology, medicinal chemistry, clinical neuroscience, mental disorders research, drug or alcohol addiction research, radiochemistry, and/or pharmacokinetics into synergistic research teams without regard to institutional affiliation.

C.  A plan should be described for decision-making regarding identification and evaluation of promising drug candidates for development.

D.  Pharmaceutical partners should include key personnel who have authority within the company to allocate resources to ensure successful completion of the proposed discovery and development efforts.

E.  Intellectual Property and Patent Rights for New Chemical Entities.  Since the discovery of new pharmacological treatments for mental disorders, drug or alcohol addiction is a major objective of this effort and active involvement by pharmaceutical laboratories is encouraged and facilitated by the existence of adequate patent coverage, it is essential that applicants provide plans to assure the protection of intellectual property for new chemical entities for the treatment of mental disorders, drug or alcohol addiction under this FOA.

Successful applicants are required to supply the following confidential materials to the NIMH, NIDA and/or NIAAA Program Officials listed under Section VII. Agency Contacts.

1.  Each applicant Group must provide a detailed description of the approach to be used for obtaining patent coverage and for licensing where appropriate, in particular where the invention may involve investigators from more than one institution.  Procedures must be described for resolution of legal problems should they arise.  Your attention is drawn to the NIH Extramural Technology Transfer Policies and Documents [http://ott.od.nih.gov/NewPages/602-rev2.htm].

2.  A formal statement of Patent Agreement among all Group members and their institutions as well as a detailed description of procedures to be followed for resolution of legal problems which may develop, must be signed and dated by the organizational official authorized to enter into patent arrangements for each Group member and member institution.  The signed agreement must be submitted prior to award to the appropriate NIMH, NIDA and/or NIAAA staff at the addresses provided under Section VII. Agency Contacts.

3.  A plan must be developed for disposition of combinatorial and compound libraries generated in Research Projects focused on discovery of new chemical entities as clinical candidates for drug development in conformance with Cooperative Agreement Terms and Conditions of Award, Section VI, Item 2. A, listed below.  The signed document must be submitted prior to award to the appropriate NIMH, NIDA and/or NIAAA staff at the addresses provided under Section VII. Agency Contacts.

4.  Prior to the award, the Principal Investigator and each Project Leader must provide a signed statement of acceptance of the participation of NIMH, NIDA and/or NIAAA staff during performance of the award as outlined under "NIH Staff Responsibilities" in the Cooperative Agreement Terms and Conditions of Award, Section VI, Item 2. A.

Note:  Do NOT submit documents 1-4 above with the application.  However, awards will not be made until these documents are received and approved by NIMH, NIDA or NIAAA.

F.  An NIH intramural scientist may not serve as the Principal Investigator of an NCDDG but may participate in a Group as a Project Leader, Scientific Core Leader, collaborator, or consultant.  However, an Intramural scientist may not receive salary, equipment, supplies, or other remuneration from this FOA.  The Intramural scientist must obtain written approval of his/her NIH Institute Scientific Director for the amount of resources that may be allocated to the project; this amount must be specified in the letter, and can not exceed $200,000 in direct costs of intramural resources.  The approval must also specify that the conduct of the project will comply with the DHHS regulations for research involving human subjects (if applicable) and with the PHS policy on vertebrate animal research.  The participation of an intramural scientist is independent of and unrelated to the role of the NIMH, NIDA and/or NIAAA Science Officer as described in the Terms and Conditions of Award.  For NCDDG applications that include NIH intramural components, the intramural resource level will be included in the total cost of the overall application.  The involvement of Intramural scientists needs to be consistent with NIH Policy. 
http://www1.od.nih.gov/oir/sourcebook/ethic-conduct/ethical-conduct-toc.htm

Section IV. Application and Submission Information


1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 435-0714, 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 on line 2 of the face page of the application form and the YES box must be checked.

Foreign Organizations

Several special provisions apply to applications submitted by foreign organizations:

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.

3. Submission Dates and Times

See Section IV.3.A for details.

3.A. Receipt, Review and Anticipated Start Dates

Letters of Intent Receipt Date(s):  February 22, 2007; August 17, 2007; January 25, 2008; August 18, 2008; January 26, 2009; August 17, 2009  
Application Receipt Date(s): March 22, 2007; September 17, 2007; February 25, 2008; September 17, 2008; February 25, 2009; September 17, 2009  
Peer Review Date(s): June/July 2007; November/December 2007; May/June 2008; November/December 2008; May/June 2009; November/December 2009
Council Review Date(s): October 2007, January 2008, October 2008, January 2009, October 2009, January 2010
Earliest Anticipated Start Date(s):  November 2007, February 2008, November 2008, February 2009, November 2009, February 2010  

3.A.1. Letter of Intent

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

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed at the beginning of this document.

The letter of intent should be sent to:

Linda Brady, Ph.D.
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
6001 Executive Boulevard, Room 7204, MSC 965
Bethesda, MD  20892-9645
Rockville, MD  20852-9645 (for express/courier service)
Telephone:  (301) 443-3563
FAX:  (301) 402-4740
Email:  lbrady@mail.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the research grant application 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 appendix materials  must be sent to:

Jean G. Noronha, Ph.D.
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6154, MSC 9609
Bethesda, MD  20892
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 443-3367
FAX:  (301) 443-4720
Email:  jnoronha@mail.nih.gov

3.C. Application Processing

Applications must be received on or before the application receipt/submission date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review.

Upon receipt applications will be evaluated for completeness by CSR. Incomplete 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 merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an application already reviewed, but such application must include an Introduction addressing the previous critique.

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

4. Intergovernmental Review
This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

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

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

6. Other Submission Requirements

SPECIFIC INSTRUCTIONS FOR PREPARING THE NCDDG U19 APPLICATION

In addition to the details described here for U19 applications, applicants also need to be aware of information described under Special Eligibility Criteria in this announcement.

Applications must be complete at the time of submission.  Applicants are encouraged to organize the application by initially presenting the face page, the abstract page with key personnel, a table of contents, summary budget pages for the entire proposal, and other documentation pertaining to the entire project.  This should be followed by an introductory section of no more than ten pages that provides a General Description of the NCDDG.  The content requirements of this section are described below.

Following the General Description(s), each component (the Research Projects and Cores, if any) should be presented individually with its accompanying individual budget and justification, biographical sketches, other support pages, and research plan.

For each Research Project there is a 25-page limit for the research plan (i.e., specific aims, background and significance, preliminary studies/ progress report, and research design and methods), as indicated in the form PHS 398.  A 3 page introduction may be included for each project in a resubmission (formerly revised or amended) application, in order to address the prior summary statement.  Appendix material limits apply to each component separately, and appendices are limited to the contents specified in the form PHS 398.  They should be bundled separately, component by component.

For each individual Research Project, the research plan needs to address:

For each core component, there is a 10-page limit.  A 1 page introduction may be included for each core in a resubmission (formerly revised or amended) application, in order to address the prior summary statement. If cores are required, the applicant must describe how each Core will contribute to the goals of the overall NCDDG as well as how each individual Research Project will draw upon a particular Core.  The description of each Core should clearly indicate the facilities, resources, services and professional skills that the facility will provide.  Moreover, clearly described information must be provided about how the collective operation of the Cores will be effected in a coherent manner.

SPECIFIC INSTRUCTIONS FOR PREPARING THE GENERAL DESCRIPTION OF THE NCDDG

The section must not exceed 10 pages, (excluding the1 page introduction for a resubmission) and should provide the following details:

SUPPLEMENTAL INSTRUCTIONS FOR NIH INTRAMURAL RESEARCHERS

NIH intramural researchers collaborating on an NCDDG must obtain the approval of his/her NIH Institute Scientific Director for participating under the terms and conditions of the PA.  A copy of that letter of approval must be provided in the application.

NIH intramural researchers submitting an Individual Research Project as a part of an NCDDG, must follow the procedures for Individual Research Projects as described above, with the following additional modifications.

Specific Instructions for Applications Requesting $500,000 (direct costs) or More per Year.

Applicants requesting $500,000 or more in direct costs for any year must carry out the following steps:

1) Contact the appropriate Institute program staff at least 6 weeks before submitting the application, i.e., as you are developing plans for the study;

2) Obtain agreement from the program staff that the Institute will accept your application for consideration for award; and,

3) Include a cover letter with the application that identifies the staff member and Institute who agreed to accept assignment of the application.

This policy applies to all investigator-initiated new (type 1), competing continuation (type 2), competing supplement, or any amended or revised version of these grant application types. Additional information on this policy is available in the NIH Guide for Grants and Contracts, October 19, 2001 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html.

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.

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

Sharing Research Resources

NIH policy expects that grant award recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

NIMH, NIDA and NIAAA are interested in ensuring that the research tools and models to evaluate therapeutics developed through this PA become readily available to the scientific community for further research, development, and application, in the expectation that this will lead to knowledge of benefit to the public.  These tools and models are ones in which there are no intellectual property rights or patent position.  In these cases, it is expected that the Principal Investigator's sharing plan will include the following elements:

1) Description of mechanisms by which program-generated research resources related to research tools and models (e.g., compounds, radioligands, synthesis protocols, analytical tools, IND filing information for clinical research tools) are distributed to qualified investigators in the scientific community; and 2) a timetable for distribution.  There should NOT be separate data sharing plans for each research component, but rather a single plan for the Group as a whole.

Applicants are invited to utilize NIH supported repositories such as the NIMH Chemical Synthesis and Drug Supply Program (http://nimh-repository.rti.org/) or the NIDA Drug Supply Program to make compounds available to the scientific community as research tools. 

Section V. Application Review Information


1. Criteria

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

2. Review and Selection Process

 Applications that are complete will be evaluated for scientific and technical merit by an appropriate review group convened by NIMH in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

The following will be considered in making funding decisions:

The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health.  Within this framework, the specific goals of this FOA are drug discovery, preclinical evaluation, and testing of new drugs to treat mental disorders, or drug or alcohol addiction, the development of pharmacologic tools for basic and clinical research, and, for mental disorders, the development and validation of models for evaluating novel therapeutics.  In the written comments reviewers will be asked to evaluate the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals.  The scientific review group will address and consider each of the following criteria in assigning the application’s overall score, weighting them as appropriate for each application.  Individual Research Projects and Cores within the NCDDG, as well as the NCDDG as a whole, will be evaluated.

REVIEW CRITERIA FOR THE NCDDG AS A WHOLE

1.  Significance.  Is the Group addressing an important problem?  If the aims of the application are achieved, what is the likelihood that it will produce a new candidate drug for development?  What will be the effect of these studies on the concepts or methods that drive this field?  To what degree does the proposed plan for discovery and testing of novel drugs, research tools, and/or preclinical models support the needs for the targeted disease?

2.  Approach.  Are the conceptual framework, design, and methods adequately developed, well integrated, and appropriate to the aims of the project?  Are the scientific disciplines represented in Research Projects and Scientific Cores adequate to achieve the NCDDG Program objectives?  Does the applicant acknowledge potential problem areas and consider alternative tactics?  Is there a sound scientific rationale for the proposed molecular or clinical targets?  Are targets, screens, and preclinical models relevant to drug discovery for mental disorders and/or drug or alcohol addiction?  If pharmaceutical partnerships are proposed, how will they facilitate the development and evaluation of candidate drugs, tools for clinical research, and model validation for testing therapeutics?

3.  Innovation.  Does the NCDDG employ novel concepts, approaches or methods?  Are the aims original and innovative?  Does the NCDDG challenge existing paradigms, develop new research tools, models, methodologies, or technologies?  Is the target under investigation for drug discovery novel?  Will new paradigms for drug discovery emerge?

4.  Investigators.  Are the Principal Investigator, Research Project Leaders, and Core Leaders appropriately trained and well suited to direct or carry out this work?  Are the time commitments for each sufficient to achieve the goals?  To what extent do these investigators have complementary skills?  Will the Research Project Leaders and their key personnel contribute unique skills to the NCDDG?  Is the work proposed appropriate to the experience level of the key personnel and other researchers?  Has the Principal Investigator demonstrated leadership in development, implementation, and management of comprehensive research programs?

5.  Environment.  Does the technical and scientific environment in which the Research Projects will be done contribute to the probability of success?  Does the proposed work take advantage of unique features of the technical and scientific expertise and employ effective collaborations?  Is there evidence of institutional support and competence of the applying Institution to serve as the Administrative Core for the Group?

  Interaction.  Are there adequate plans for ensuring effective intra-Group communication, interaction, cohesiveness, and coordination among the PI, Research Project Leaders, and NIH Science Officers?  Do the investigators state their willingness to collaborate extensively and share information fully?  Do the investigators state their willingness to abide by the policies stated in the Terms and Conditions of the Cooperative Agreement?

Resource Sharing Plan.  How appropriate are the proposed plans for making research tools, synthesis protocols, analytical tools, preclinical models, IND filing information, or other resources generated under the project widely available to the scientific community?  Are the plans and timetable for distribution adequate for effective dissemination of the proposed resources?

REVIEW CRITERIA FOR RESEARCH PROJECTS

1.  Significance.  Does this study address an important problem?  If the aims of the application are achieved, how will scientific knowledge or technology be advanced?  What will be the effect of these studies on the concepts or methods that drive this field?

2.  Approach.  Are the conceptual framework, design, and methods adequately developed, well integrated, and appropriate to the aims of the project?  Are the scientific disciplines represented in Research Projects adequate to achieve the objectives?  Does the applicant acknowledge potential problem areas and consider alternative tactics?  Is the plan to optimize lead structures adequate to ensure that the most efficacious drug will result?  If pharmaceutical partnerships are proposed, how will they facilitate the discovery and development of drugs and evaluation of research tools or models?

3.  Innovation.  Does the Research Project employ novel concepts, approaches or methods?  Are the aims original and innovative?  Does the project challenge existing paradigms or develop new tools, methodologies, or technologies?

4.  Investigators.  Are the Research Project Leader and key personnel appropriately trained and well suited to direct or carry out this work?  Is the Project Leader's time commitment sufficient to achieve the goals?  Is the work proposed appropriate to the experience level of the key personnel and other researchers?  Have collaborations been established or consultants identified to provide the appropriate depth and breadth of expertise required for the project?

5.  Environment.  Does the technical and scientific environment in which the work will be done contribute to the probability of success? Does the proposed work take advantage of unique features of the technical and scientific expertise and employ effective collaborations?

Management of the Group.  Does the PI have previous experience of the ability to manage an integrated scientific enterprise?  Do other members of the Group have experience that will facilitate achieving the desired research outcomes.

REVIEW CRITERIA FOR CORES

1.  Is the utility of the Core to the NCDDG adequately described?   Does each Core provide essential facilities or services to two or more Research Projects judged to have scientific merit?

2.  Is the quality of the facilities or services provided by the Core adequately described?

3.  Are the qualifications and experience of the personnel involved in the Core adequate to accomplish the goals of the Core?

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 priority score:
Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section F of the PHS Form 398 research grant application instructions will be assessed.

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

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

Applications from Foreign Organizations: Does the project present special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources will be assessed? 

Resubmission Applications (formerly “revised/amended” applications): Are the responses to comments from the previous scientific review group adequate? Are the improvements in the resubmission application appropriate?

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.

2.D. Sharing Research Resources

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

The sharing plan will be considered part of the scientific methodology for carrying out the research and, as such, the adequacy of the plan will be considered in determining funding priorities.  Reviewers will assess the adequacy of the proposed plan as detailed in the review criteria section.  Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

3. Anticipated Announcement and Award Dates
N/A

Section VI. Award Administration Information


1. Award Notices

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

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

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

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

2. Administrative and National Policy Requirements

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

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

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement (U19), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined above. The tasks and activities are described more fully below.

Integration into the on-going program of the National Cooperative Drug Discovery Groups (NCDDG) is anticipated.  Principal Investigators and Research Project Leaders will be expected to attend an annual NCDDG meeting to review progress and share information among awardees.

2.A.1. Principal Investigator Rights and Responsibilities

a.  The Principal Investigator will have primary authority and responsibility to define objectives and approaches and to plan and conduct the proposed research.  She/he will assume responsibility and accountability to the applicant organization and to the NIMH, NIDA and/or NIAAA for performance and proper conduct of all research supported in the NCDDG, including the NIH intramural component, if applicable, in accordance with the Terms and Conditions of Award. The Principal Investigator will be a member of the Executive Committee.

b.  Intramural research scientists participating as Research Project Leaders or collaborators have the same rights and responsibilities as other members of the Group.

c.  The Awardee Institution and/or Research Project Leader's Institution will retain primary custody of and have primary rights to data as specified under either the NIMH, NIDA and/or NIAAA approved Intellectual Property Patent Rights Agreements for New Chemical Entities or the data and research resource sharing plans (described above).  The Government, via the NIMH, NIDA or NIAAA Science Officer, will have access to data generated under this cooperative agreement and may periodically review the data consistent with current DHHS, PHS, and NIH policies.  Timely publication of major findings by the Group members is encouraged.  Publication or oral presentation of work done under this agreement will require appropriate acknowledgment of NIMH, NIDA and/or NIAAA support, including the assigned cooperative agreement award number.

d.  Ownership of compound libraries and/or combinatorial libraries for drug discovery acquired during the course of the research rests with the Group.  Prior to award, the Group(s) must formulate a plan for final disposition of the compounds and ownership rights in the event that the compounds are transferred to other parties who make discoveries using them.  This plan is to be approved by NIMH, NIDA and/or NIAAA.

e.  It is the intention that new chemical entities be fully evaluated as potential candidate drugs for mental health disorders, drug or alcohol addiction or as potential research tools, after the Group has concluded its evaluation and before the compounds are transferred to other parties for evaluation in other therapeutic areas.  The Groups must follow the NIMH, NIDA and/or NIAAA approved Intellectual Property Patent Rights Agreements for New Chemical Entities or the data and research resource sharing plans.

2.A.2. NIH Responsibilities

During performance of the award, the role of the NIMH, NIDA and/or NIAAA Science Officer is one of substantial involvement above and beyond the normal program stewardship role of a Program Official.  The Science Officer interacts scientifically with the Group and may provide appropriate assistance, including assisting in research planning, suggesting studies within the scope of the Group's objectives and research activities, presenting experimental findings to the Group from published sources or from relevant contract projects, participating in the design of experiments agreed to by the Group, participating in the analysis of results, and advising in management and technical performance.  The Science Officer(s) will be a member(s) of the Executive Committee.  In all cases, the role of NIMH, NIDA and/or NIAAA will be to assist and facilitate and not to direct activities.

The NIMH, and/or NIAAA Science Officer(s) can recommend to their Institutes to utilize their drug development resources (e.g., CNS receptor screening, chemical synthesis, and toxicology services) in support of the NCDDG Group research activities if such resources are required on an occasional basis.  The following is a list of resources that are readily available and may be supplied if they become desirable during performance.  It is not anticipated that requests of services will be considered as a continuing need.

a.  Reference compounds for standardization of test systems, as analytical standards, and for related purposes.

b.  Data from testing conducted in resource contract laboratories.

c.  Laboratory testing capacity, whenever appropriate and possible, in NIMH's and NIDA's current contract based preclinical testing programs.  The Group is expected to provide sufficient test material for such testing.

d.  Additional needed resources such as test materials and information that may not otherwise be available to the Group.

Additionally, an agency program official or Institute program officer will be responsible for the normal scientific and programmatic stewardship of the award, including monitoring implementation of the data and research resource sharing plans and will be named in the award notice.

2.A.3. Collaborative Responsibilities

A governing Executive Committee composed of the PI, Research Project Leaders, Core Directors, and NIH Institute Science Officers will be established in each NCDDG to assist in monitoring and developing the scientific content and direction of the program.  The Executive Committee members will meet periodically to review progress, plan and design research activities, and establish priorities.  The frequency of meetings, not fewer than two per year, will be determined by the Principal Investigator who will be responsible for scheduling the time and place (generally at one of the performance sites) and for preparing concise proceedings or minutes (two or three pages) which will be delivered to the members of the Group within 30 days of the meeting.

a.  The principal end products of NCDDG activities for NIMH and NIAAA are expected to include:  1) the discovery and testing of new chemical entities, optimization of lead compounds, IND-directed toxicology, safety pharmacology to support phase 1 studies, and the identification of clinical candidates for the treatment of mental disorders or alcohol addiction; 2) research tools; and 3) preclinical models to evaluate novel therapeutics.  Cost-sharing is encouraged for IND-directed toxicity and safety studies of drug candidates.  Private sources of funding should be identified for GMP synthesis, formulation, and IND filing costs.  Toxicology and safety studies exceeding 28 days in duration and phase II efficacy trials are beyond the scope of this FOA.

b.  The principal end products of NCDDG activities for NIDA are expected to include:  1) the discovery of ligands  for target validation studies and potentially for development as pharmacotherapies for drug addiction,  2) as research tools to advance research in the treatment development domain,  and 3)  preclinical models to evaluate novel therapeutics.  Studies required for IND-targeted preclinical development (GMP synthesis, formulation, toxicology) are generally beyond the scope of this PAR for NIDA.  Such development through private venture capital is encouraged.

c.  NIMH and/or NIAAA will retain the option to cross-file or independently file an application for an investigational clinical trial (e.g., an IND application to the United States Food and Drug Administration) of any clinical research tool or invention resulting from these NIH supported cooperative agreements.  Reports of data generated by the Group or any of its members required for inclusion in IND applications and for cross-filing purposes shall be submitted promptly by the Principal Investigator to the NIH Institute Science Officer upon request.  Such reports shall include background information, methods, results, and conclusions.

2.A.4. Arbitration Process

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

3. Reporting

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

Section VII. Agency Contacts


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

1. Scientific/Research Contacts:

NIMH

Linda Brady, Ph.D.
Director, Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
6001 Executive Boulevard, Room 7204, MSC 9641
Bethesda, MD  20892-9641
Telephone:  (301) 443-3563
FAX:  (301) 402-4740
Email:  lbrady@mail.nih.gov

NIDA

David Shurtleff, Ph.D.
Director, Division of Basic Neuroscience & Behavioral Research
National Institute on Drug Abuse
6001 Executive Boulevard, Room 4282, MSC 9555
Bethesda, MD 20892-9555
Telephone:  (301) 443-1887
FAX:  (301) 594-6043

Email:  dshurtle@mail.nih.gov

NIAAA

For questions concerning behavioral models of facets of alcoholism:

Mark Egli, Ph.D.
Division of Neuroscience and Behavior
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 2059, MSC 9304
Bethesda, MD 20892-9304
Telephone:  (301) 594-6382
FAX:  (301) 443-1650
Email: megli@mail.nih.gov

For questions concerning molecular targets:

Roger G. Sorensen, Ph.D., M.P.A
Division of Neuroscience and Behavior
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 2053, MSC 9304
Bethesda, MD 20892-9304
Telephone: (301) 443-2678
FAX:  (301) 443-1650
Email: rsorense@mail.nih.gov

2. Peer Review Contacts:

David Armstrong, Ph.D.
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Blvd, , Room 6138, MSC 9606
Bethesda, MD 20892-9605
Telephone:  (301) 443-3534
Email:  armstrda@mail.nih.gov

3. Financial or Grants Management Contacts:

NIMH

Rebecca Claycamp, M.S., CRA
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6122, MSC 9605
Bethesda, MD  20892-9605
Telephone:  (301) 443-2811
FAX: (301) 443-6885
Email: rclaycam@mail.nih.gov

NIDA

Pam Fleming
Grants Management Branch
National Institute on Drug Abuse
6101 Executive Boulevard, Room 260, MSC 8403
Bethesda, MD 20892-8403
Telephone: (301) 443-6710
FAX: (301) 594-6849
Email: pfleming@mail.nih.gov

NIAAA

Judy Fox
Chief, Grants Management Branch
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 3023, MSC 9304
Bethesda, MD  20892-9304
Telephone:  (301) 443-4704
FAX: (301) 443-3891
Email: jfox@mail.nih.gov

Section VIII. Other Information


Required Federal Citations

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

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

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

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

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

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

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

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

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

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

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

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

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles.  Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

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

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

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

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


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NIH Funding Opportunities and Notices


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