NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS FOR THE TREATMENT OF MOOD DISORDERS OR 
NICOTINE ADDICTION (NCDDG-MD/NA)

Release Date:   August 27, 2002 (see addendum NOT-MH-02-011)

RFA:  MH-03-008

National Institute of Mental Health (NIMH)
 (http://www.nimh.nih.gov/)
National Institute on Drug Abuse (NIDA)
 (http://www.nida.nih.gov/)

Letter of Intent Receipt Date:  October 25, 2002
Application Receipt Date:  November 26, 2002

THIS RFA CONTAINS THE FOLLOWING INFORMATION

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

PURPOSE 

The intent of this solicitation is to invite applications from academic and 
pharmaceutical industry investigators interested in participating with National 
Institute of Mental Health (NIMH) and the National Institute on Drug Abuse 
(NIDA) in a National Cooperative Drug Discovery Group (NCDDG-MD/NA) Program to 
accelerate innovative drug discovery, the development of pharmacologic tools for 
basic and clinical research in mood disorders or nicotine addiction, and, in the 
case of mood disorders, the development and validation of models for evaluating 
novel therapeutics.  NIMH and NIDA are interested in jointly advancing the 
discovery of new ligands because we anticipate that there are targets in common 
and overlap in the expertise that can be brought to bear.

The goal of the NCDDG-MD/NA Program is to establish long-term partnerships 
between NIH, academia, and industry that will advance the development and 
testing of fundamentally new, rationally designed medications and treatments for 
mental disorders and nicotine addiction.

Academic and/or pharmaceutical industry components of each NCDDG-MD/NA should 
contribute unique scientific expertise towards the common goal of translating 
basic science findings into innovative pharmacologic treatments for mental 
disorders and drug 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-MD/NA.  Scientists from 
foreign institutions and NIH Intramural laboratories may participate in some 
aspects, as noted in other sections of this application.

The NCDDG-MD/NA Program is most appropriate for applications that include 
collaborations, Research Projects or core components from academia and the 
private sector (e.g., pharmaceutical, chemical, or biotechnological companies).  
It is anticipated that the interaction of academic and non-profit research 
institutions with industry and NIH via the NCDDG-MD/NA model will:  1) 
accelerate the discovery of new therapeutics for mood disorders and nicotine 
addiction; 2) increase the availability of pharmacologic research tools for 
basic and clinical research; and 3) facilitate the development and validation of 
models to evaluate novel therapeutics in mood disorders.

Small businesses without academic and/or industry partners are encouraged to 
respond to parallel Program Announcements:  Pharmacologic Agents and Drugs for 
Mental Disorders (SBIR Award) 
[http://grants.nih.gov/grants/guide/pa-files/PA-02-027.html], Development of PET 
and SPECT Ligands for Brain Imaging (SBIR Award) 
[http://grants.nih.gov/grants/guide/pa-files/PA-02-028.html], and Innovative 
Toxicology Models: SBIR/STTR - Addendum to PA-02-075, Notice NOT-MH-02-005 
[http://grants.nih.gov/grants/guide/notice-files/NOT-MH-02-005.html].

RESEARCH OBJECTIVES

A.  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 mood 
and substance abuse disorders.  With the wealth of potential new drug targets, 
the opportunity exists to accelerate the process of discovery to make quantum 
leaps toward novel and effective treatments for mood disorders (depression and 
bipolar disorder) and drug addiction.

NIMH recently convened a panel of experts to assess the state of the science and 
to identify opportunities and priorities in key areas of research relevant to 
mood disorders.  The following priorities identified in the area of 
pharmacologic treatment development for mood disorders are relevant to this RFA:  
1) development of neurochemical tools for understanding disease pathophysiology 
(e.g., expanding chemical repositories to increase the availability of imaging 
ligands and probes for basic and clinical research); 2) exploration, development, 
and evaluation of cellular, circuit-based, and pathophysiology-based models for 
drug development; and 3) facilitation of partnerships between NIMH, academia, 
and industry to support innovative approaches for drug discovery and the 
development of behavioral assays using the NCDDG-MD/NA model established by the 
National Cancer Institute (NCI).  The NIMH Strategic Plan for Mood Disorders 
Research is available at http://www.nimh.nih.gov/strategic/strategicplanmenu.cfm.

NIDA's interests are broadly consistent with the NIMH Strategy Plan (above), but 
with a particular interest at this time in drug discovery for nicotine addiction.  
The use of tobacco products is believed to be due in large part to addiction to 
nicotine, which acts through nicotinic cholinergic receptors (nAChRs).  In 
recent years there have been real advances in our understanding of the structure 
of the various subunits of these receptors, and of the ways in which the 
subunits combine to form diverse nAChR subtypes.  In particular, evidence 
suggests that the widely distributed alpha4/beta2 subtype plays a central role 
in nicotine addiction.  In addition, studies have suggested roles for other 
subtypes, for example the homomeric alpha7 nAChR and various complex heteromeric 
receptors that have been shown to modulate the release of addiction-relevant 
neurotransmitters, or are of interest because of their anatomical locations.  
Establishment of a program to develop ligands that target nAChR subtypes is 
compelling for several reasons.  First, the response of nAChRs to nicotine is 
complex and subtype dependent; this complexity may provide an opportunity to 
develop ligands that may be particularly useful in treating nicotine addiction.  
Second, it is possible that ligands with a particular profile of action at 
nAChRs may be developed   for example, partial agonists   a profile that may 
ultimately be useful in developing the molecule as a medication for treatment of 
nicotine addiction.  Third, it is possible that ligands with a particular 
pharmacokinetic profile may be developed that would support their use in novel 
nicotine replacement devices.  In general, novel ligands developed for the 
nAChR target may afford greater specificity and safety in treatment.  Finally, 
ligands with a particular nAChR receptor profile will be of use as tools with 
which to advance knowledge of the basic processes of nicotine addiction.

In addition, there have been concrete advances in our understanding of the 
circuitry involved in nicotine addiction, in behavioral phenomena that associate 
with and/or modulate addiction, and in the effects of nicotine on CNS processes 
that may be associated with addictive behavior, such as learning and plasticity.  
Furthermore, knowledge of drug addiction in general suggests that processes such 
as stress may modulate addictive behaviors.  For many of these, evidence for the 
involvement of specific neurotransmitter systems and receptors exists; hence 
targets for ligand development exist.

Finally with respect to nicotine addiction, a number of valid cellular and 
animal models are currently available.  It is therefore expected that responsive 
groups will logically include a program to evaluate the efficacy of novel 
ligands in the appropriate models.  Examples of components of such a program 
could include, but are not limited to, tests of the ability of novel ligands to 
modulate cellular processes of plasticity in reward-relevant regions of the 
brain, assessment of the behavioral profile of nicotinic ligands in tests of
reinforcement, relapse and withdrawal, and measurement of the effects of novel 
ligands on neurotransmitter release.

The NCDDG-MD/NA Program will support broad, innovative, multidisciplinary, multi-
project approaches to the discovery of new, rationally based treatments for mood 
disorders and nicotine 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 
RFA.  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 being solicited.

B.  Research Scope

The objective of this RFA is to establish NCDDG-MD/NA 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 mood and nicotine addiction.  The NCDDG-MD/NA 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 mood disorders and nicotine addiction.  Research 
projects directed at identifying novel targets within signaling pathways 
involved in the regulation of emotion, reward, addiction, and cognition are 
encouraged.

NIMH is especially interested in drug discovery for bipolar disorder and 
depression, and in the development of models for testing such drugs.  As noted 
above, NIDA is interested in drug discovery primarily for nicotine addiction.  
Certain molecular targets may have relevance beyond drug addiction and, in 
particular nicotine addiction (e.g., pain, cognitive function).  At the present 
time, and for this initiative NIDA is not interested in the development of 
agents for these purposes; the sole target is drug addiction.  For this 
initiative, NIDA is NOT interested in research to develop new models of drug 
addiction.  NIDA has an existing medication development program built around the 
dopamine system and further work in this area is NOT sought under this RFA.  
However, dopaminergic components of action may be relevant, for example, as part 
of research needed to understand the mechanisms of action of bupropion and 
related compounds that may be useful in treating tobacco (nicotine) and possibly 
other substance abuse disorders.

Molecular targets of high programmatic interest both in terms of novel 
therapeutics and research tools include, but are not limited to, the following:

o  Nicotinic cholinergic receptor (nAChR) subtypes, especially alpha4/beta2 and 
alpha7, and other AChRs implicated in nicotine reward
o  Metabotropic glutamate receptor subtypes
o  Receptors mediating the action of bupropion
o  Serotonin receptor subtypes, especially 5-HT2A selective antagonists, and 
ligands for 5-HT6 and 5-HT7
o  Neurokinin receptors, NK1, NK2, NK3
o  Corticotropin releasing factor receptors, CRH R1, CRH R2
o  Mood stabilizers
o  Intracellular targets:  BDNF, GSK-3B inhibitors, protein kinase inhibitors, 
transcription factors

Potential ligands of interest to NIMH and NIDA might be identified by their 
receptor properties (e.g., 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 the principal aim of this initiative.  The use of chemical 
libraries, structural biology and computer modeling of molecular targets to 
screen for compounds with activity at selected targets are examples of 
responsive approaches.  If applicants do choose to synthesize compounds, they 
are encouraged to synthesize a small number, and to evaluate these compounds 
before making new analogs.  Extensive structure-activity-relationship studies 
are not encouraged.  Lead optimization using combinatorial chemistry or other 
innovative technologies is encouraged.

A program to evaluate the efficacy of novel ligands for nAChRs in valid cellular 
and animal models of nicotine addiction needs to be considered.  Such evaluation 
would logically address questions of the ability of the ligands to substitute 
for nicotine itself, to attenuate nicotine's reinforcing properties, as well as 
to measure the reinforcing properties of the novel ligands per se.

Responsive applicants may outline plans for the development and evaluation of 
cellular, circuit, or pathophysiology based models for validation of novel 
targets (preliminary proof-of-concept) for mood disorders, and drug discovery 
and the identification of compounds as potential candidates for drug development 
for mood disorders and nicotine addiction.  The development of new chemical 
identities is a mandatory component.

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 clinical research tools, models, and novel 
therapeutics.

Note:  The development of analogs of established or well-studied agents for the 
treatment of mental disorders and/or substance abuse is not responsive to this 
RFA.  Subsequent studies required for development of new treatments (e.g., 
formulation development, large-scale production for clinical trials, or 
toxicology in support of Investigational New Drug (IND) applications, etc.) as 
well as early phase clinical trials, are beyond the scope of this RFA.

Please contact program staff listed under Inquiries to determine program 
priorities and molecular targets of interest to NIMH and NIDA.

MECHANISM OF SUPPORT

This RFA will use National Institute of Health (NIH) U01 and U19 cooperative 
agreement award mechanisms.  As an applicant you will be solely responsible for 
planning, directing, and executing the proposed project.  This RFA is a one-time 
solicitation.  The anticipated award date is July 1, 2003.

If the NCDDG-MD/NA Program is funded and successful, a follow-up RFA may be 
issued to facilitate renewal of the Program.

The NIH U01 and U19 are cooperative agreement award mechanisms in which the 
Principal Investigator retains the primary responsibility and dominant role for 
planning, directing, and executing the proposed project, with NIH staff being 
substantially involved as a partner with the Principal Investigator, as 
described under the section "Cooperative Agreement Terms and Conditions of 
Award".

The total project period requested for applications submitted in response to the 
present RFA may not exceed 5 years.

FUNDS AVAILABLE

The NIMH and NIDA intend to commit approximately $3,000,000 (total costs) in FY 
2003 to fund three to five new grants in response to this RFA (NIMH $1,500,000; 
NIDA $1,500,000).  Because the nature and scope of the research proposed may 
vary, it is anticipated that the size of the awards will also vary.  

Although the financial plans of the IC(s) provide support for this program, 
awards pursuant to this RFA are contingent upon the availability of funds and 
the receipt of a sufficient number of meritorious applications.  

ELIGIBLE INSTITUTIONS
 
You may submit an application if your institution has any of the following 
characteristics:

o For-profit or non-profit organization 
o Public or private institutions, such as universities, colleges, hospitals, and 
laboratories 
o Domestic
o Units of State and local governments
o Eligible agencies of the Federal government

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to carry out 
the proposed research is invited to work with his/her institution to develop an 
application for support.  Individuals from under-represented racial and ethnic 
groups as well as individuals with disabilities are encouraged to apply for NIH 
programs.

DEFINITIONS

AWARDEE.  The institution to which the NCDDG-MD/NA award (U19 or U01) is issued.

CORE (ADMINISTRATIVE).  An administrative unit located at the Principal 
Investigator's institution that coordinates all NCDDG-MD/NA activities.  It is 
separately budgeted from the PI's Research Project (if any) and oversees support 
for activities pertinent to the NCDDG-MD/NA, such as travel for intra-group 
meetings.

CORE (SCIENTIFIC).  A separately budgeted scientific service component that 
provides essential facilities or services to two or more of the proposed 
Research Projects.  Core components typically use established procedures or 
protocols rather than generating new research.  An NIH intramural laboratory may 
participate as a Scientific Core.

CORE LEADER.  The director of a scientific core component who is responsible for 
the conduct of that core.

NATIONAL COOPERATIVE DRUG DISCOVERY GROUP (NCDDG-MD/NA).  An NCDDG-MD/NA must 
include a Research Project to conceptualize, discover, and evaluate NEW CHEMICAL 
ENTITIES for the treatment of mood disorders (NCDDG-MD) and/or nicotine 
addiction (NCDDG-NA).  The Groups may also include Research Projects to:  1) 
generate pharmacologic TOOLS for basic and clinical research on mood disorders 
and nicotine addiction (e.g., drugs or radioligands for targets implicated in 
the pathophysiology of mood disorders or nicotine addiction; and/or 2) for mood 
disorders, develop and validate cellular, circuit, or pathophysiology based 
MODELS for evaluating novel therapeutics.  An NCDDG-MD/NA is encouraged to 
include high risk/high impact projects on drug discovery for mood disorders 
and/or nicotine addiction in one or more of the areas specified above:  NEW 
CHEMICAL ENTITIES (required), RESEARCH TOOLS, and/or MODELS (mood disorders 
only).

An NCDDG-MD/NA can apply using either the U01 or U19 mechanisms.  A Group of 
collaborators focused on one or two Research Projects without Cores should use 
the U01 mechanism.  Groups with three-to-five Research Projects as well as Core 
components should use the U19 mechanism.

The development and strengthening of partnerships between scientists from 
academia and the pharmaceutical industry is a highly desirable outcome of this 
RFA and is strongly encouraged.  Pharmaceutical scientists are encouraged to 
actively participate as Principal Investigator, Project Leader, and/or key 
personnel/collaborators in one or more Research Projects within an NCDDG-MD/NA.  
Scientists from foreign institutions and NIH Intramural laboratories may 
participate as Project Leaders or as collaborators in Research Projects or 
scientific cores.

NIH COORDINATOR.  A scientist from the NIMH and/or NIDA extramural program staff 
who has substantial involvement in the Group above and beyond normal program 
stewardship.  The Coordinator interacts scientifically with the Group and 
facilitates the role of NIMH and/or NIDA as partner in the Group.  The 
Coordinator will be appointed after award by NIMH and/or NIDA.

NIH PROGRAM OFFICIAL.  A staff member of NIMH and/or NIDA who provides normal 
stewardship and guidance for the overall NCDDG-MD/NA Program within the NIMH or 
NIDA and ensures that the NCDDG-MD/NA Program maintains its relevance to the 
NIMH and NIDA mission for drug discovery and treatment development research.  
The Program Official also may serve as an NIH Coordinator for a Group.

PRINCIPAL INVESTIGATOR.  The scientist who is designated by the applicant 
institution to direct the NCDDG-MD/NA.  The PI will assume responsibility and 
accountability to the applicant institution and to the NIMH and NIDA for the 
performance and proper conduct of the NCDDG-MD/NA in accordance with the terms 
and conditions specified in this RFA.  It is expected that the PI will 
contribute at least a 25% effort to the Group.  Foreign scientists and NIH 
intramural scientists may not be a Principal Investigator.

RESEARCH PROJECT.  A research component headed by a Project Leader within an 
NCDDG-MD/NA with a separate, detailed research plan and budget.  Foreign 
institutions and NIH intramural laboratories may participate in a Research 
Project.

RESEARCH PROJECT LEADER.  A senior scientist with proven independent research 
capabilities who serves as director of one of the scientific Research Projects 
of the Group and is responsible for the scientific conduct of that program.  The 
Principal Investigator of the Group may be a Project Leader.  Foreign scientists 
and NIH intramural scientists may be Project Leaders.

SPECIAL REQUIREMENTS

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

B.  A proposed Group can consist of scientific collaborators focused on one or 
two Research Projects without Cores (U01 mechanism) or at least three 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, mood disorders research, drug 
addiction research, radiochemistry, and 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 mood disorders and 
nicotine 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 mood disorders and/or nicotine addiction under this RFA.

Successful applicants are required to supply the following confidential 
materials to the NIMH and NIDA Program Officials listed under INQUIRIES.

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 Drs. Linda Brady and/or William Corrigall at the addresses 
provided under INQUIRIES.

3.  A plan must be developed for disposition of combinatorial and compound 
libraries generated in Research Projects focused on discovery of NEW CLINICAL 
ENTITIES as clinical candidates for drug development in conformance with TERMS 
AND CONDITIONS OF AWARD, Item 1. D, listed below.  The signed document must be 
submitted prior to award to Drs. Linda Brady and/or William Corrigall at the 
addresses provided under INQUIRIES.

4.  Prior to the award, the Principal Investigator and each Project Leader must 
provide a signed statement of acceptance of the participation of NIMH and/or 
NIDA staff during performance of the award as outlined under "NIMH and/or NIDA 
Staff Responsibilities" below.

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 and/or 
NIDA.

F.  DATA SHARING PLAN FOR RESEARCH TOOLS AND MODELS TO EVALUATE THERAPEUTICS

The NIH is also interested in ensuring that the RESEARCH TOOLS and MODELS 
developed through this RFA 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 Data 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://www.sri.com/biosciences/nimh/) or the NIDA Drug Supply Program 
to make compounds available to the scientific community as research tools.  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.  The sharing plan as 
approved, after negotiation with the applicant when necessary, will be a 
condition of the award.

G.  An NIH intramural scientist may not serve as the Principal Investigator of 
an NCDDG-MD/NA 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 RFA.  
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 and/or NIDA Coordinator as 
described below in TERMS AND CONDITIONS OF AWARD.  For NCDDG-MD/NA 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 

COOPERATIVE AGREEMENT TERMS AND CONDITIONS OF AWARD

The following terms and conditions will be incorporated into the award statement 
and provided to the Principal Investigator as well as the institutional official 
at the time of award.  Failure to abide by any of the Terms and Conditions of 
Award pertaining to awardee responsibilities stipulated in this Section may 
result in a reduction of funding, withholding of support, suspension or 
termination of the award.

These special Terms and Conditions of Award are in addition to and not in lieu 
of otherwise applicable OMB administrative guidelines, DHHS Grant Administration 
Regulations at 45 CFR parts 74 and 92, and other DHHS, PHS, and NIH Grant 
Administration policy statements.

1.  Cooperative Agreement Mechanism

The administrative and funding instrument used for this program is a cooperative 
agreement (U01 or U19), an "assistance" mechanism (rather than an "acquisition" 
mechanism) in which substantial NIH scientific and/or programmatic involvement 
with the awardee is anticipated during performance of the activity.  Under the 
cooperative agreement, the NIH purpose is to support and/or stimulate the 
recipient's activity by involvement in and otherwise working jointly with the 
award recipient in a partner role, but not to assume direction, prime 
responsibility, or a dominant role in the activity.  Consistent with this 
concept, the dominant role and prime responsibility for the activity resides 
with the Principal Investigator for the Group, although specific tasks and 
activities in carrying out these studies may be shared between the awardee and 
the NIH Coordinators assigned to the NCDDG-MD/NA.  The tasks and activities are 
described more fully below.

2.  Awardee 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 and/or NIDA for performance and proper conduct of 
all research supported in the NCDDG-MD/NA, including the NIH intramural 
component, if applicable, in accordance with the Terms and Conditions of Award.

b.  The Group members will meet periodically to review progress, plan and design 
research activities, and establish priorities.  Intramural research scientists 
participating as Research Project Leaders or collaborators have the same rights 
and responsibilities as other members of the Group.  The NIMH and/or NIDA 
Coordinators and/or Program Officials may attend.  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.  The role of the NIMH and/or NIDA Coordinator is one of 
substantial involvement above and beyond the normal role of a Program Official, 
including, for example, 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, and participating in the analysis of results.

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 and/or NIDA approved INTELLECTUAL PROPERTY PATENT RIGHTS 
AGREEMENTS FOR NEW CHEMICAL ENTITIES or the DATA SHARING PLAN FOR RESEARCH TOOLS 
AND MODELS TO EVALUATE THERAPEUTICS (described above).  The Government, via the 
NIMH and/or NIDA Coordinator, 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 and/or NIDA 
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 and/or NIDA.

e.  It is the intention that new chemical entities be fully evaluated as 
potential candidate drugs for mental health disorders and nicotine 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 and/or NIDA approved 
INTELLECTUAL PROPERTY PATENT RIGHTS AGREEMENTS FOR NEW CHEMICAL ENTITIES or the 
DATA SHARING PLAN FOR RESEARCH TOOLS AND MODELS TO EVALUATE THERAPEUTICS.

3.  NIMH and NIDA Staff Responsibilities

NIMH and/or NIDA Coordinators have substantial involvement in the Group above 
and beyond normal program stewardship.  The Coordinator interacts scientifically 
with the Group.  During performance of the award, NIMH and/or NIDA may provide 
appropriate assistance by participating in the design of activities, advising in 
the selection of sources for resources, staff, etc., and advising in management 
and technical performance.  In all cases, the role of NIMH and/or NIDA will be 
to assist and facilitate and not to direct activities.

The NIMH/NIDA Coordinator(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-MD/NA 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.

The NIMH/NIDA Program Officials are responsible for normal stewardship and 
monitoring implementation of the Data Sharing Plan for Research Tools and Models 
for Evaluating Therapeutics.

4.  Collaborative Responsibilities

The following are Collaborative Responsibilities of the Group and the NIMH and 
NIDA Coordinators.

a.  The principal end products of NCDDG-MD/NA activities are expected to 
include:  1) the discovery of new chemical entities, optimization of lead 
compounds, and the identification of clinical candidates for the treatment of 
mood disorders and/or nicotine addiction; as well as 2) research tools; and 3) 
preclinical models to evaluate novel therapeutics.  Subsequent toxicity and 
safety studies of drug candidates and clinical developmental work through other 
resources are encouraged.

b.  NIMH and/or NIDA 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 NIMH and/or NIDA 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 NIMH and/or NIDA 
Coordinator upon request.  Such reports shall include background information, 
methods, results, and conclusions.

5.  Arbitration

Any disagreement that may arise on scientific/programmatic matters (within the 
scope of the award, including the NIH intramural component), between the awardee 
and the NIMH and/or NIDA may be brought to arbitration.  An arbitration panel 
will be composed of three members:  one Group designee, one NIMH and/or NIDA 
designee, and a third designee with expertise in the relevant area chosen by the 
two designees.  This special arbitration procedure in no way affects the 
awardee's right to appeal an adverse action in accordance with PHS regulations 
at 42 CFR Part 50, Subpart D, and DHHS regulations at 45 CFR Part 16.

WHERE TO SEND INQUIRIES

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

o  Direct your questions about scientific/research issues to:

Linda Brady, Ph.D.
Chief, Molecular and Cellular Neuroscience Research Branch
Chief, Neuropharmacology & Drug Discovery and Clinical Therapeutics Program
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
6001 Executive Boulevard, Room 7185, MSC 9641
Bethesda, MD  20892-9641
Rockville, MD  20852-9641 (for express/courier service)
Telephone:  (301) 443-5288
FAX:  (301) 402-4740
Email:  [email protected]

William Corrigall, Ph.D.
Chief, Translational Research Branch
Director, Nicotine and Tobacco Addiction Program
Division of Neuroscience and Behavioral Research
National Institute of Drug Abuse
6001 Executive Boulevard, Room 4282, MSC 9555
Bethesda, MD  20892-9555
Rockville, MD  20852 (for express/courier service)
Telephone:  (301) 435-1324
FAX:  (301) 594-6043
Email:  [email protected]

o  Direct your questions about peer review issues to:

Michael Kozak, Ph.D.
Chief, Extramural Review Branch
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6138, MSC 9608
Bethesda, MD  20892-9608
Rockville, MD  20852-9608 (for express/courier service)
Telephone:  (301) 443-1340
FAX:  (301) 443-4720
Email:  [email protected]

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

Carol Robinson
Grants Management Branch
National Institute of Mental Health
6001 Executive Boulevard, Room 6118
Bethesda, MD  20892
Telephone:  (301) 443-3858
FAX:  (301) 443-6885
Email:  [email protected]

Gary Fleming, J.D., M.A.
Grants Management Branch
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3131
Bethesda, MD  20892
Telephone:  (301) 443-6710
FAX:  (301) 594-6847
Email:  [email protected]

LETTER OF INTENT

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

o  Descriptive title of the proposed research
o  Name, address, and telephone number of the Principal Investigator
o  Names of prospective Project Leaders, other key personnel, and their 
respective participating institutions
o  Number and title of this RFA

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

Linda Brady, Ph.D.
Chief, Molecular and Cellular Neuroscience Research Branch
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
6001 Executive Boulevard, Room 7185, MSC 9641
Bethesda, MD  20892-9641
Rockville, MD  20852-9641 (for express/courier service)
Telephone:  (301) 443-5288
FAX:  (301) 402-4740
Email:  [email protected]

APPLICATION PROCEDURES

Applications must be prepared using the PHS 398 research grant application 
instructions and forms available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive 
format.  For further assistance contact GrantsInfo, Telephone (301) 710-0267, 
Email: [email protected].  Potential applicants are strongly encouraged to 
contact NIMH/NIDA program staff early in the planning process.

1.  SPECIFIC INSTRUCTIONS FOR PREPARING THE NCDDG-MD/NA AWARD U01 APPLICATION

In addition to the details described here for U01 applications, applicants also 
need to be aware of information described under SPECIAL REQUIREMENTS 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-MD/NA.  The content 
requirements of this section are described in #3 below.

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

For each Research Project component, 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.  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: 

o  The major goals and objectives of the project and their relationship to the 
overall effort of the NCDDG-MD/NA.

o  The status of current research efforts, the limitations of existing 
approaches, and how the research questions posed relate to the objectives of the 
particular project and the NCDDG-MD/NA as a whole.

o  The feasibility of the proposed experiments, the advantages of new 
methodologies (if any), the potential pitfalls, alternative approaches, the 
means of assessing success of the research to meet the objectives of the project 
and the NCDDG-MD/NA as a whole.

2.  SPECIFIC INSTRUCTIONS FOR PREPARING THE NCDDG-MD/NA AWARD U19 APPLICATION

In addition to the details described here for U19 applications, applicants also 
need to be aware of information described under SPECIAL REQUIREMENTS 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-MD/NA.  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.  
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: 

o  The major goals and objectives of the project and their relationship to the 
overall effort of the NCDDG-MD/NA.

o  The status of current research efforts, the limitations of existing 
approaches, and how the research questions posed relate to the objectives of the 
particular project and the NCDDG-MD/NA as a whole.

o  The feasibility of the proposed experiments, the advantages of new 
methodologies (if any), the potential pitfalls, alternative approaches, the 
means of assessing success of the research to meet the objectives of the project 
and the NCDDG-MD/NA as a whole.

For each core component, there is a 10-page limit.  If cores are required, the 
applicant must describe how each Core will contribute to the goals of the 
overall NCDDG-MD/NA 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.

3.  SPECIFIC INSTRUCTIONS FOR PREPARING THE GENERAL DESCRIPTION OF THE 
NCDDG-MD/NA

This section is to accompany both U01 and U19 applications.  The section must 
not exceed 10 pages, and should provided the following details:

o An overview of the proposed NCDDG-MD/NA Group, its central theme and goals; 
this overview should describe the general objectives, and explain the proposed 
contribution of each of the individual Research Projects and Cores (if any) 
towards achieving the objectives of the Group.  The administrative arrangements 
and research support should be described.  In particular, when more than one 
institutional site is involved, a detailed description and supporting 
documentation for the administrative arrangements must be included.  Detailed 
information on collaborations, facilities, and resources must also be provided.

o  A clear description of how each component Research Project is required for 
the attainment of the NCDDG-MD/NA Program's objectives, including available 
professional and technical personnel to permit efficient and successful conduct 
of the proposed research, and description of the contribution of each to 
fulfillment of group objectives.  The name, organization, and scientific 
discipline of the 
Principal Investigator, Research Project Leaders, and other key personnel should 
be included.  A clear description of the interrelationships among the members of 
the group needs to be made.

o  Evidence needs to be provided that each component Research Project and the 
Group as a whole have available facilities required for conduct of the proposed 
research.

o  A plan to assure the maintenance of close collaboration and effective 
communication among members of the group that will include letters of commitment 
to this plan by all Research Project Leaders.  Include plans for scheduling 
group meetings, notifying group members (including the NIMH and NIDA), and 
documenting and disseminating group meeting proceedings.

o  Description of the steps that will be taken to ensure successful completion 
of the NCDDG-MD/NA's research should a key member leave the Group.

4.  SUPPLEMENTAL INSTRUCTIONS FOR NIH INTRAMURAL RESEARCHERS

NIH intramural researchers collaborating on an NCDDG-MD/NA must obtain the 
approval of his/her NIH Institute Scientific Director for participating under 
the terms and conditions of the RFA.  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-MD/NA, must follow the procedures for Individual Research Projects 
as described above, with the following additional modifications.

o  On the Face Page, fill out only items 1., 2., 3. (leave 3c. blank), 4., and 
5.  The remainder of the items should be left blank, and the application must 
not be signed by either the PI or an NIH Institute official.  

o  The Individual Research Project PI must obtain the approval of his/her NIH 
Institute Scientific Director for participating as a component of the 
NCDDG-MD/NA under the terms and conditions of the RFA.  A copy of that letter of 
approval must be provided in the application.

o  The Research Project component should NOT contain the "Other Support" pages.  

o  The individual budget pages should supply the time and effort for each 
project participant, but no other budget figures should be included.  The 
resources available for the Research Project and the research environment should 
be carefully described, but no budget figures should be included.  The NIH 
Institute Scientific Director, as part of the letter of approval for 
participation, must verify that no more than $200,000 direct costs of intramural 
resources will be allocated to the project described in the application, and 
provide assurance 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.

FOR ALL APPLICATIONS

The RFA label available in the PHS 398 (rev. 5/2001) application form must be 
affixed to the bottom of the face page of the application.  Type the RFA number 
on the label.  Failure to use this label could result in delayed processing of 
the application such that it may not reach the review committee in time for 
review.  In addition, the RFA title and number must be typed on line 2 of the 
face page of the application form and the YES box must be marked.  The RFA label 
is also available at: http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.

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
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, two additional copies of the application 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:  [email protected]

Applications must be received by the application receipt date listed in the 
heading of this RFA.  If an application is received after that date, it will be 
returned to the applicant without review.  Supplemental documents containing 
significant revision or additions will not be accepted.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed by the CSR for completeness, and by 
NIMH/NIDA program staff for responsiveness.  Incomplete or non-responsive 
applications will be returned to the applicant without review.

Applications that are complete and responsive to the RFA will be evaluated for 
scientific and technical merit by an appropriate peer review group convened by 
the NIMH in accordance with the review criteria stated below.  As part of the 
initial merit review, all applications will:

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

REVIEW CRITERIA

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 RFA are drug discovery and 
preclinical evaluation of new drugs to treat mood disorders and nicotine 
addiction, the development of pharmacologic tools for basic and clinical 
research, and, for mood disorders, the development and validation of models for 
evaluating novel therapeutics.  In the written comments reviewers will be asked 
to discuss the following aspects of 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 overall score, weighting them as appropriate for each 
application.  Individual Research Projects and Cores within the NCDDG-MD/NA, as 
well as the NCDDG-MD/NA as a whole, will be evaluated.

REVIEW CRITERIA FOR THE NCDDG-MD/NA 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 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-MD/NA Program objectives?  Does the applicant 
acknowledge potential problem areas and consider alternative tactics?  Are 
targets, screens, and preclinical models relevant to mood disorders and/or 
nicotine 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-MD/NA employ novel concepts, approaches or 
methods?  Are the aims original and innovative?  Does the NCDDG-MD/NA 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-MD/NA?  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?

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

7.  Data 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?

6.  Management of the Group.  Especially for the U19 mechanism, 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.  The utility of the Core to the NCDDG-MD/NA.  Each Core must provide 
essential facilities or services to two or more Research Projects judged to have 
scientific merit.

2.  The quality of the facilities or services provided by the Core.

3.  The qualifications and experience of the personnel involved in the Core.

ADDITIONAL CONSIDERATIONS

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

o  The review group will critically examine the budget requested for each 
Research Project, Core, and overall NCDDG-MD/NA and will recommend an 
appropriate budget and period of support.

o  The adequacy of plans to include genders, minorities and their subgroups, and 
children as appropriate for the scientific goals of the research.  Plans for the 
recruitment and retention of subjects will also be evaluated.

o  The reasonableness of the proposed budget and duration in relation to the 
proposed research.

o  The adequacy of the proposed protection for humans, animals or the 
environment, to the extent they may be adversely affected by the project 
proposed in the application.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:    October 25, 2002
Application Receipt Date:         November 26, 2002
Peer Review Date:                 February/March 2003
Council Review:                   May 2003
Earliest Anticipated Start Date:  July 1, 2003

AWARD CRITERIA

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

o  Scientific and technical merit (as determined by peer review)
o  Availability of funds
o  Programmatic priorities

REQUIRED FEDERAL CITATIONS 

MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD:  Research components 
involving Phase I and II clinical trials must include provisions for assessment 
of patient eligibility and status, rigorous data management, quality assurance, 
and auditing procedures.  In addition, it is NIH policy that all clinical trials 
require data and safety monitoring, with the method and degree of monitoring 
being commensurate with the risks (NIH Policy for Data Safety and Monitoring, 
NIH Guide for Grants and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS:  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 biomedical and behavioral 
research projects involving human subjects, unless a clear and compelling 
rationale and justification are 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 AMENDMENT "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research - Amended, October, 2001," published in the NIH Guide for Grants and 
Contracts on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete
copy of the updated Guidelines 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) all 
investigators must report accrual and progress in conducting analyses, as 
appropriate by sex/gender and/or racial/ethnic group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:  It 
is the policy of NIH that children (i.e., individuals under the age of 21) must 
be included in all human subjects research, conducted or supported by the NIH, 
unless there are scientific and ethical reasons not to include them.  This 
policy applies to all initial (Type 1) applications submitted for receipt dates 
after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines" on the Inclusion of Children as Participants in 
Research Involving Human Subjects that was published in the NIH Guide for Grants 
and Contracts, March 6, 1998, and is available at the following URL address:  
http://grants.nih.gov/grants/guide/notice-files/not98-024.html.

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

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

Applicants may wish to place data collected under this RFA 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.

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

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

AUTHORITY AND REGULATIONS:  This program is described in the Catalog of Federal 
Domestic Assistance No. 93.242 (NIMH) and 93.279 (NIDA).  Awards are made under 
authorization of Sections 301 and 405 of the Public Health Service Act as 
amended (42 USC 241 and 284) and administered under NIH grants policies and 
Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.  This program is not 
subject to the intergovernmental review requirements of Executive Order 12372 or 
Health Systems Agency review.

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and promote the non-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.

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