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 and Development Groups (NCDDDG) for the Treatment of Mental Disorders, Drug or Alcohol Addiction (U01/U19)

Announcement Type
This is a reissue of PAR-07-159.

Update: The following updates relating to this announcement have been issued:

Looking ahead: As part of the Department of Health and Human Services' implementation of e-Government the NIH will gradually transition each research grant mechanism to electronic submission through Grants.gov and the use of the SF 424 Research and Related (R&R) forms. For more information and an initial timeline, seehttp://grants.nih.gov/grants/guide/notice-files/NOT-OD-06-035.html. NIH will announce each grant mechanism change in the NIH Guide to Grants and Contracts (http://grants.nih.gov/grants/guide/index.html).

Program Announcement (PA) Number: PAR-08-238

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

Key Dates - New /Revised
Letters of Intent Receipt Date(s):Sep 3, 2008; Jan 24, 2009; Aug 17, 2009; Jan 24, 2010; (Additional Date May 24, 2010 per NOT-MH-10-012); Aug 17, 2010; Jan 24, 2011; (Additional Date May 24, 2011 per NOT-MH-10-012)
Application Receipt Date(s):Oct 3, 2008; Feb 24, 2009; Sep 17, 2009; Feb 24, 2010; (Additional Date June 24, 2010 per NOT-MH-10-012); Sep 17, 2010; Feb 24, 2011 (Additional Date June 24, 2011 per NOT-MH-10-012)
Peer Review Date(s):Feb 2009, Jun 2009, Jan/Feb 2010, Jun 2010, (Additional Date Oct 2010 per NOT-MH-10-012), Jan 2011, Jun 2011, (Additional Date Oct 2011
per NOT-MH-10-012)
Council Review Date(s):May 2009, Oct 2009, May 2010, Oct 2010, (Additional Date Jan 2011 per NOT-MH-10-012), May 2011, Oct 2011, (Additional Date Jan 2012
per NOT-MH-10-012)
Earliest Anticipated Start Date(s):Jul 2009, Dec 2009, Jul 2010, Dec 2010, (Additional Date April 2011 per NOT-MH-10-012), Jul 2011, Dec 2011, (Additional Date April 2012 per NOT-MH-10-012)
Expiration Date: Changed to May 8, 2011 (Per NOT-OD-11-048); (New Expiration Date June 25, 2011 per NOT-MH-10-012), Original Date February 25, 2011

Key Dates - Old
Release Date: August 14, 2008
Letters of Intent Receipt Date(s): September 3, 2008; January 24, 2009; August 17, 2009
Application Receipt Date(s): October 3, 2008; February 24, 2009; September 17, 2009
Peer Review Date(s): February 2009; June 2009; January/February 2010
Council Review Date(s):May 2009; October 2009; May 2010
Earliest Anticipated Start Date(s): July 2009; December 2009; July 2010
Additional Information To Be Available Date (Url Activation Date): Not Applicable
Expiration Date: September 18, 2009

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 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 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
A. Cooperative Agreement Terms and Conditions of Award
1. Principal Investigator Rights and Responsibilities
2. NIH Responsibilities
3. Collaborative Responsibilities
4. Arbitration Process
3. Intellectual Property and Patent Rights for New Chemical Entities
4. 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 and Development Group (NCDDDG) program. The objectives of this program are to advance the discovery, preclinical development, and proof of concept testing of new, rationally based candidate medications to treat mental disorders or drug or alcohol addiction and to develop novel ligands 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. Partnerships between academia and industry are strongly encouraged.

Each NCDDDG program should consist of a multi-disciplinary team of scientists with appropriate expertise to further the development and evaluation of novel compounds. Scientists from both academia and pharmaceutical industry are encouraged to participate within an NCDDDG; scientists from foreign institutions and NIH Intramural laboratories may participate in some aspects, as noted in other sections of this funding opportunity. It is anticipated that the interaction of academic and non-profit research institutions with industry and NIH via the NCDDDG model will: 1) accelerate the discovery and development of new therapeutics for mental disorders, drug or alcohol addiction; 2) increase the availability of pharmacologic research tools (including imaging agents) for basic and clinical research; 3) facilitate the development and validation of models to evaluate novel therapeutics for mental disorders; 4) increase the availability of new IND-ready compounds suitable for testing in humans; and 5) facilitate the development and validation of new clinical measures or biomarkers suitable for use in human proof of concept trials of novel therapeutics for mental disorders or alcohol addiction.

The goal of the NCDDDG 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, 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 great strides toward novel and effective treatments for mental disorders, drug or alcohol addiction.

NIMHs objectives and interests for the NCDDDG program

NIMHs objective for the NCDDDG 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 NCDDDG research projects can focus on one or more molecular targets and include two or more of the following projects or components ranging from ligand discovery and testing in preclinical models to human proof of concept studies. Projects or components can focus on:

For proof of concept studies, priority will be given to first-time or early trials of IND-ready agents with pre-clinical profiles suggesting the possibility of therapeutic effect in human disease. Testing of novel indications for already approved agents will be considered, based on strong theoretical rationale and/or public health significance.

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.

Specific go/no go decision-making points and quantitative milestones should be included for assessing progress and success toward the therapeutic development goal, including a proposed plan for further development of novel compounds or drug candidates; these milestones will be used by program staff in assessing yearly progress and continued funding.

NIDAs objectives and interests for the NCDDDG 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 NIDAs perspective, the NCDDDG 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 groups will include a program to evaluate the efficacy of novel ligands in appropriate models. Components of NIDA-relevant NCDDDG 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 NCDDDG 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.

NIAAAs objectives and interests for the NCDDDG program

NIAAAs interests for the NCDDDG 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 to be used as tools to research biological processes contributing 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. Applicants are strongly encouraged to discuss proposals involving toxicity, safety and pharmacokinetic as well as proof of concept studies of novel compounds with NIAAA staff listed in Section VII.1. Agency Contact(s) Scientific/Research Contacts.

Compounds currently approved by the Food and Drug Administration for treating alcohol dependence have distinct mechanisms of action and target distinct behavioral aspects of problem alcohol consumption. Disulfiram (Antabuse), an aldehyde dehydrogenase inhibitor 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, an opiate receptor antagonist, is thought to diminish alcohols positive reinforcing effects, particularly in people with mu opiate receptor polymorphisms. Acamprosates therapeutic mechanism of action is unclear, but it is thought that acamprosate attenuates the enhanced glutamatergic transmission during alcohol withdrawal and may work best at alleviating craving and relapse in abstinent patients. 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 medications that interact at additional targets, and that treat additional behavioral facets of alcoholism.

Current pharmaceutical strategies for treating alcohol use disorders are broadly designed towards developing agents that: a) modify alcohol intoxication, reduce the pleasurable effects of alcohol or increase 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. Alcohols multiple biological effects, and the many physical and behavioral alterations that occur following chronic alcohol use and abuse offer opportunities for developing additional pharmacotherapies.

NCDDDG is 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 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, substance P), and agents that alter signal transduction pathways (such as protein kinase effectors, protein phosphatase inhibitors, G-protein regulators and calcium signaling disruptors).

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.

The identification and pursuit of agents towards novel targets previously un-recognized or understudied for the treatment of alcohol abuse disorders are especially encouraged. In particular, NIAAA encourages applications focusing on agents that alleviate craving and dysphoria during protracted abstinence, and agents effective in patients who have co-morbid psychiatric illnesses (e.g., schizophrenia, bipolar disorder). Applications that essentially propose to further extend the testing of established or well-studied compounds and strategies are not appropriate for this FOA.

Summary

In summary, the NCDDDG 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, model development, and clinical testing. 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 NCDDDG 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 NCDDDG 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, drug or alcohol addiction.

Molecular targets that applicants may wish to consider include, but are not limited to, the following. Receptors: adenosine; adrenergic: alpha 1, alpha 2; cannabinoid: CB1, CB2; corticotropin releasing hormone: CRF R1, CRF R2; dopamine: D1, D3, D4, D5; estrogen; GABA A subunits; GABA ion channel; GABA B; glutamatergic, glycine site; metabotropic glutamate subtypes and other glutamate receptor subtypes; muscarinic subunits; neurokinin receptors: NK1, NK2, NK3; heteromeric neuronal nicotinic receptor subunits; NMDA subunits; opioid receptors: mu, delta, kappa; serotonin: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2C, 5-HT5, 5-HT6, 5-HT7; orexin (hypocretin); oxytocin; vaspressin receptors;

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 are important goals 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 appropriate 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. Although NIDA, NIMH and NIAAA will not rule out the use of combinatorial chemistry in NCDDDG projects, applicants proposing them should provide appropriate justification that this approach to compound synthesis is desirable.

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. Applicants should outline proposed plans for further development of promising compounds or clinical candidates that are generated by the NCDDDG program.

Note: The development of analogs of established or well-studied agents for the treatment of mental disorders, drug or alcohol abuse is not appropriate for 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. 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) (NOT-RM-08-005, PAR-07-358) 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 announcement (FOA) will use the NIH Research Project Cooperative Agreement (U01) and NIH Multi-Project Cooperative Agreement (U19) award mechanisms. The applicant 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). A detailed categorical budget for the "Initial Budget Period" and the "Entire Proposed Period of Support" is to be submitted with the application.

The U01 and U19 are cooperative agreement award mechanisms. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) 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 IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds.

Facilities and administrative 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. 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

An NIH intramural scientist may not serve as the PD/PI of an NCDDDG 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 Project Scientist as described in the Terms and Conditions of Award. For NCDDDG 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.

Applicants may submit a resubmission application, but such application must include an Introduction addressing the previous peer review critique (Summary Statement).

Applicants may submit a renewal application.

Applicants may submit more than one application, provided that each application is scientifically distinct.

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

3. Submission Dates and Times

See Section IV.3.A. for details.

Key Dates - New
Letters of Intent Receipt Date(s): Sep 3, 2008; Jan 24, 2009; Aug 17, 2009; Jan 24, 2010; Aug 17, 2010; Jan 24, 2011
Application Receipt Date(s): Oct 3, 2008; Feb 24, 2009; Sep 17, 2009; Feb 24, 2010; Sep 17, 2010; Feb 24, 2011
Peer Review Date(s): Feb 2009, Jun 2009, Jan/Feb 2010, Jun 2010, Jan 2011, Jun 2011
Council Review Date(s): May 2009, Oct 2009, May 2010, Oct 2010, May 2011, Oct 2011
Earliest Anticipated Start Date(s): Jul 2009, Dec 2009, Jul 2010, Dec 2010, Jul 2011, Dec 2011
Expiration Date: February 25, 2011

3.A. Receipt, Review and Anticipated Start Dates
Letters of Intent Receipt Date(s): September 3, 2008; January 24, 2009; August 17, 2009
Application Receipt Date(s): October 3, 2008; February 24, 2009; September 17, 2009
Peer Review Date(s): February, 2009; June 2009; January/February 2010
Council Review Date(s): May 2009; October 2009; May 2010
Earliest Anticipated Start Date(s): July 2009; December 2009; July 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 in Section IV.3.A.

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
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 the 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/ 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. However, the NIH will accept a resubmission application, but such application must include an Introduction addressing the critique from the previous review.

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.

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/archive/grants/policy/nihgps_2003/index.htm.)

6. Other Submission Requirements and Information

Special Instructions/Research Strategy Page Limitations

In addition to the details described here for U01 and U19 applications, applicants also need to be aware of information described under Special Eligibility Criteria in Section III.3 of this announcement.

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 (i.e., the Special Requirements). This should be followed by an introductory section of no more than twelve pages that provides an Overall Research Strategy of the NCDDDG. The content requirements of this section are described below.

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

A. Overall Research Strategy of the NCDDDG (U01 and U19):

The section must not exceed 12 pages, (excluding the 1 page introduction for a resubmission) and should provide the following details:

B. Specific Instructions for Individual Research Projects (U01 and U19). For each Research Project there is a 12-page limit for the Research Strategy as indicated in the form PHS 398.

For each individual Research Project, the Research Strategy needs to address:

C. Specific Instructions for Cores (U19). For each Core component, there is a 12-page limit. A 1 page introduction may be included for each core in a resubmission 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 NCDDDG 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.

D. Instructions for NIH Intramural Researchers. An NIH intramural researcher collaborating on an NCDDDG 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 NCDDDG, must follow the procedures for Individual Research Projects as described above, with the following additional modifications.

Cooperative Agreement

Awardees must agree to the Cooperative Agreement Terms and Conditions of Award in Section VI.2.A Award Administration Information.

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 (excluding consortium F&A costs) must carry out the following steps:

1) Contact the IC program staff at least 6 weeks before submitting the application, i.e., as plans are being developed for the study;

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

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

This policy applies to all new, renewal, revision, or resubmission applications. See NOT-OD-02-004, October 16, 2001.

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. 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


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 submitted for this funding opportunity will be assigned on the basis of established PHS referral guidelines to the ICs for funding consideration.

Applications that are complete will be evaluated for scientific and technical merit by (an) appropriate scientific review group(s) convened by the NIMH, 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:

This award will include special terms and conditions that differ from the agency's usual terms and conditions. See also Section IV.5, Funding Restrictions.

Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications. The following will be considered in making funding decisions:

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health..In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, and weighted as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a meritorious impact/priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Individual Research Projects and Cores within the NCDDDG, as well as the NCDDDG as a whole, will be evaluated.

Review Criteria for the Overall NCDDDG (U01 and U19)

Overall Impact. Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five core review criteria, and additional review criteria (as applicable for the project proposed).

Core Review Criteria. Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance: Does this NCDDDG address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? 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? What is the likelihood that it will produce a new candidate drug for development?

Investigator(s): Are the PD/PI(s) and other key personnel (including 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? Does the investigative team bring complementary and integrated expertise to the NCDDDG? 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? Has the Principal Investigator demonstrated leadership in development, implementation, and management of comprehensive research programs?

Innovation: Is the project original and innovative? Does the NCDDDG challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the NCDDDG develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area? Is the target under investigation for drug discovery novel? Will new paradigms for drug discovery or models emerge?

Approach: Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?
Are the scientific disciplines represented in Research Projects and Scientific Cores adequate to achieve the NCDDDG Program objectives? 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?

Environment: Does the technical and scientific environment in which the work will be done contribute to the probability of success? Does the proposed work benefit from the unique features of the technical and scientific environment, or subject populations, or employ effective collaborations? Is there evidence of institutional support and competence of the applying Institution to serve as the Administrative Core for the Group? Does the clinical research team demonstrate a track record in successfully recruiting subjects into clinical trials and research studies and completing proposed studies within projected timelines?

In addition to the above review criteria, the following criterion will be addressed and considered in the determination of scientific merit and the rating.

Interaction. Are there adequate plans for ensuring effective intra-Group communication, interaction, cohesiveness, and coordination among the PI, Research Project Leaders, and NIH Project Scientists? 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?

Review Criteria for Research Projects (U01 and U19)

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

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?

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?

Investigator(s): 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?

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 or 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 (U19)

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:

Resubmission Applications (formerly revised/amended applications): When reviewing a Resubmission application (formerly called an amended application), the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Protections for Human Subjects: For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.


Inclusion of Women, Minorities, and Children: When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

Vertebrate Animals: The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia.

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 impact/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 impact/priority score, unless noted otherwise in the FOA. Program staff within the IC will be responsible for monitoring the resource sharing.

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?

3. Anticipated Announcement and Award Dates

Not Applicable

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.

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.

A formal notification in the form of a Notice ofAward (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.

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/archive/grants/policy/nihgps_2003/index.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/archive/grants/policy/nihgps_2003/index.htm).

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, 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 below.

2.A.1. Project Director/Principal Investigator (PD/PI) 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 NCDDDG, 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 Steering 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 Project Scientist, 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 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 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 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, or NIAAA Project Scientist is one of substantial involvement above and beyond the normal program stewardship role of a Program Official. The Project Scientist 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 Project Scientist(s) will be a member(s) of the Steering Committee. In all cases, the role of NIMH, NIDA, or NIAAA will be to assist and facilitate and not to direct activities.

The NIMH or NIAAA Project Scientist(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 NCDDDG 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 or in the NIH Rapid Access to Interventional Development (NIH-RAID) program. 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 Institute Program Official 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 Steering Committee composed of the PI, Research Project Leaders, Core Directors, NIH Project Scientist(s), and NIH Program Official will be established in each NCDDDG to assist in monitoring and developing the scientific content and direction of the program. The Steering 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 PI/PD 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 NCDDDG 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 I studies, identification of clinical candidates for the treatment of mental disorders or alcohol addiction, and/or phase II efficacy studies; 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, IND filing costs, and toxicology and safety studies exceeding 28 days in duration.

b. The principal end products of NCDDDG 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 FOA for NIDA. Such development through the NIH RAID program or 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 Project Scientist 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: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3 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 may be facilitated by the existence of appropriate patent coverage, it is essential that applicants provide plans to address the handling 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 handling intellectual property 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://inventions.nih.gov].

2. A formal statement of Intellectual Property 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 intellectual property 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 Section VI.2.A - Cooperative Agreement Terms and Conditions of Award, 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 PD/PI and each Project Leader must provide a signed statement of acceptance of the participation of NIMH, NIDA or NIAAA staff during performance of the award as outlined under "NIH Staff Responsibilities" in Section VI.2.A - Cooperative Agreement Terms and Conditions of Award.

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.

4. Reporting

When multiple years are involved, 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


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

Questions about preclinical drug and tool discovery for mental disorders, toxicology and safety studies, and phase I human studies should be directed to:

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
Email: lbrady@mail.nih.gov

Questions about proof of concept studies for novel interventions or IND-ready therapeutics for mental disorders in adult populations should be directed to:

Mi Hillefors, M.D., Ph.D.
Division of Adult Translational Research and Treatment Development
National Institute of Mental Health
6001 Executive Boulevard, Room 7125, MSC 9632
Bethesda, MD 20892-9632
Telephone: (301) 443-2738
Email: hillefom@mail.nih.gov

Questions about proof of concept studies for novel interventions or IND-ready therapeutics mental disorders in children and adolescents should be directed to:

Margaret Grabb, Ph.D.
Division of Developmental Translational Research
National Institute of Mental Health
6001 Executive Boulevard, Room 7201, MSC 9645
Telephone: 301-443-3563
E-mail: mgrabb@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
Email: dshurtle@mail.nih.gov

NIAAA

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
Email: megli@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
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
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
Email: jfox@mail.nih.gov

Section VIII. Other Information


Required Federal Citations

Vertebrate Animals:
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 impact/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/

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/archive/archive/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.

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.

Inclusion of Women, Minorities, and Children:
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-09-116.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.

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 investigators 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/.


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