COOPERATIVE DRUG DEVELOPMENT GROUP (CDDG) FOR THE TREATMENT OF SERIOUS MENTAL 
ILLNESS

RELEASE DATE:  May 4, 2004

RFA NUMBER:  RFA-MH-05-003

EXPIRATION DATE:  August 26, 2004

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH)
 (http://www.nih.gov)

COMPONENT OF PARTICIPATING ORGANIZATION:
National Institute of Mental Health (NIMH)
 (http://www.nimh.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.242

LETTER OF INTENT RECEIPT DATE:  July 23, 2004
APPLICATION RECEIPT DATE:  August 25, 2004

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 OF THIS RFA

The intent of this solicitation is to invite applications from academic and 
pharmaceutical/biotechnology industry investigators interested in participating 
with the National Institute of Mental Health (NIMH) in a Cooperative Drug 
Development Group (CDDG) program.  The goal of the CDDG is to support proof-of-
concept studies of novel mechanism drug candidates and promising investigational 
new drugs (IND) for the treatment of serious mental disorders.  The CDDG will 
specifically focus on testing drugs directed at novel targets for mood disorders, 
schizophrenia, eating disorders, obsessive-compulsive disorder, fragile x, autism, 
and other serious mental disorders.  The CDDG will support studies to rapidly 
assess safety and tolerability in normal human subjects and preliminary efficacy 
studies in the target patient population.  The proof-of-concept, early phase II or 
other studies such as clinical dose optimization, pharmacokinetics, and 
pharmacodynamics studies, should determine with reasonable certainty whether or not 
a drug candidate is sufficiently safe and effective to warrant further clinical and 
commercial development.

These data will be essential for fostering partnerships between academic 
investigators and the private sector (small businesses, pharmaceutical, and 
biotechnology companies) to further test the drug candidate in future larger-scale, 
longer-term studies in the target population.  The goal of the CDDG is to foster 
these long-term partnerships between NIMH, academia, and industry that will advance 
the development and testing of fundamentally new, rationally designed medications 
and treatments for serious mental disorders.

Academic and/or pharmaceutical industry components of each CDDG should contribute 
unique scientific expertise towards the common goal of translating basic science 
findings into innovative pharmacological treatments for serious mental disorders.  
Each partnership or group must consist of a multi-disciplinary team of scientists 
with appropriate expertise to address the development and evaluation of novel IND-
ready compounds for testing in humans.  Scientists from both academia and 
pharmaceutical industry are encouraged to participate within a CDDG.  Scientists 
from foreign institutions and NIH Intramural laboratories may participate in some 
aspects, as noted in other sections of this application.

The CDDG 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 
NIMH via the CDDG model will:  1) accelerate the development of new therapeutics 
for mood disorders, schizophrenia, eating disorders, obsessive-compulsive disorder, 
fragile x, autism, and other serious mental disorders; 2) increase the availability 
of new IND-ready compounds suitable for testing in humans; and 3) facilitate the 
development and validation of new clinical measures or biomarkers suitable for use 
in human proof-of-concept trials of novel therapeutics for mood disorders, 
schizophrenia, eating disorders, obsessive-compulsive disorder, fragile x, autism, 
and other serious mental disorders.

Small businesses without academic and/or industry partners are encouraged to 
respond to related Program Announcements:  Pharmacologic Agents and Drugs for 
Mental Disorders (SBIR Award) 
[http://grants.nih.gov/grants/guide/pa-files/PA-02-027.html] 
and Development of PET and SPECT Ligands for Brain Imaging (SBIR Award) 
[http://grants.nih.gov/grants/guide/pa-files/PA-02-028.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 serious 
mental illness.  With the wealth of potential new drug targets, the opportunity 
exists to accelerate the process of drug discovery and development to make quantum 
leaps toward novel and effective treatments for mood disorders, schizophrenia, 
eating disorders, obsessive-compulsive disorder, fragile x, autism, and other 
serious mental illnesses.

Limited support for early human studies of novel drug candidates is a rate-limiting 
step in the development of novel therapeutics for serious mental illness.  The CDDG 
will complement the National Cooperative Drug Discovery Groups for the Treatment of 
Mood Disorders and Nicotine Addiction (NCDDG-MD/NA) program 
(http://grants.nih.gov/grants/guide/pa-files/PAR-04-009.html) which supports 
innovative drug discovery, research tool and model development, but does not 
include support for early phase human clinical testing.

The CDDG is envisioned as a NIMH cross-divisional program to rapidly assess the 
safety and efficacy of promising drug candidates and new indications for IND-ready 
drugs.  The CDDG program will fill the gap that currently exists between NIMH’s 
Division of Neuroscience and Basic Behavioral Science (DNBBS) preclinical drug 
discovery efforts, and the Division of Services and Intervention Research’s (DSIR) 
clinical effectiveness trials networks.

The following priorities identified in the area of pharmacologic treatment 
development for serious mental illness are relevant to this RFA:  1) human proof-
of-concept studies of new-mechanism IND-ready pharmacological agents targeting mood 
disorders, schizophrenia, eating disorders, obsessive-compulsive disorder, fragile 
x, autism, and other serious mental disorders; 2) exploration, development, and 
evaluation of novel clinical endpoints and/or biomarkers of potential value in 
establishing proof-of-concept in humans; and 3) facilitation of partnerships 
between NIMH, academia, and industry to support innovative approaches for drug 
development and the development of novel behavioral assays; and 4) studies to 
clarify the viability of further development of novel therapeutic approaches.

The CDDG will support broad, innovative, multidisciplinary, multi-project 
approaches to the development of new, rationally based treatments for serious 
mental illness.  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 NIMH 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 IND-ready pharmacological agents to be investigated, will be 
selected by the applying group.

B.  Research Scope

The objective of this RFA is to establish CDDGs to conduct innovative, high impact 
clinical research focused on the development of IND-ready pharmacological agents 
targeting novel molecular targets implicated in the pathophysiology of serious 
mental illness.  The CDDG serves as a vehicle for pharmaceutical and academic 
scientists to pool intellectual and material resources for the translation of basic 
science findings into the evaluation of new mechanism-of-action drug candidates.  
Groups are encouraged to select molecular targets and IND-ready agents for drug 
development based on recent findings in basic and clinical neuroscience, pre-
clinical research, and animal model research relevant to the understanding of 
serious mental illness.  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 
encouraged.

Potential pharmacological agents of interest to NIMH might be identified by their 
receptor properties (e.g., partial agonists, agonists, or antagonists), solubility, 
pharmacokinetics, oral or CNS bioavailability, pre-clinical profiles, or other 
characteristics to support their use as potential therapeutics for mental illness.

The testing in humans of novel mechanism therapeutics is the principal aim of this 
initiative.  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 might 
be considered, based on strong theoretical rationale and/or public health 
importance.

Responsive applicants may outline plans for the development and evaluation of new 
therapeutic agents for serious mental illness and the identification of compounds 
as potential candidates for drug development.  The application should demonstrate 
how the proposed studies will generate critical data sufficient to determine 
whether further development of the putative therapeutic agent is warranted.  The 
testing of new IND-ready pharmacological agents or approved agents in clinical 
populations is a mandatory element.  If proof of concept is already available for 
the agent selected for testing, the proposed phase II trial should be sufficiently 
powered to clarify the viability of further development.

It is anticipated that the interaction of academic and non-profit research 
institutions with NIMH 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 is not responsive to this RFA.

MECHANISM OF SUPPORT

This RFA will use the National Institute of Health (NIH) cooperative agreement 
(U01, U19) 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 February 2005.

If the CDDG 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 for applications submitted in response to this RFA may not 
exceed 5 years.

FUNDS AVAILABLE

The NIMH intends to commit approximately $2,000,000 (total costs) in FY 2005 to 
fund three to five new grants in response to this RFA.  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 NIMH 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; Scientists from foreign institutions and NIH Intramural laboratories 
may participate as Project Leaders or as collaborators in Research Projects or 
scientific cores
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 CDDG award (U19 or U01) is issued.

CORE (ADMINISTRATIVE).  An administrative unit located at the Principal 
Investigator's institution that coordinates all CDDG activities.  It is separately 
budgeted from the PI's Research Project (if any) and oversees support for 
activities pertinent to the CDDG, 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.

COOPERATIVE DRUG DEVELOPMENT GROUP (CDDG).  A CDDG must include a Research Project 
to evaluate a new pharmacological agent for the treatment of serious mental 
illness.  The Groups may also include Research Projects to:  1) conduct clinical 
dose optimization; 2) pharmacokinetics, and 3) pharmacodynamics studies as part of 
a research program that aims to determine with reasonable certainty whether a drug 
candidate is sufficiently safe and effective to warrant further clinical and 
commercial development.

A CDDG 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 a CDDG.  

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

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

PRINCIPAL INVESTIGATOR.  The scientist who is designated by the applicant 
institution to direct the CDDG.  The PI will assume responsibility and 
accountability to the applicant institution and to the NIMH for the performance and 
proper conduct of the CDDG in accordance with the terms and conditions specified in 
this RFA.  It is expected that the PI will contribute at least a 20% 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 CDDG 
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.

STEERING COMMITTEE.  A governing Steering Committee composed of the PI, Research 
Project Leaders, Core Directors, external scientific advisors, and NIMH 
Coordinator(s) will be established in each CDDG to assist in monitoring and 
development of the scientific content and direction of the program.  The Steering 
Committee will meet at least twice a year.  The frequency of meetings, not fewer 
than two per year, will be determined by the PI 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.  
Plans for organizing a Steering Committee should be described in the 
application, but potential members should not be contacted until after an 
award has been made, and the names of potential members should not be listed 
in the application.  

SPECIAL REQUIREMENTS

A.  The CDDG objectives and goals should be relevant to and compatible with the 
NIMH priorities for innovative drug discovery and  development for serious mental 
illness as specified in this RFA.  Applicants should describe their plans to 
accommodate the stated CDDG requirements, criteria, and NIMH 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 some or all of 
the diverse scientific disciplines within clinical neuroscience, neuropharmacology, 
psychopathology research, brain imaging, radioligand development, and 
pharmacokinetics, and will form into synergistic research teams without regard to 
institutional affiliation.

C.  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.

D.  INTELLECTUAL PROPERTY AND PATENT RIGHTS FOR NEW CHEMICAL ENTITIES
Since the development of new pharmacological treatments for serious mental illness 
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 pharmacological agents for the treatment of serious 
mental illness under this RFA.

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

1.  Each applicant Group must provide a detailed description of the approach 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 and related sites [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 either Dr. Wayne Fenton (DMDBA) or Dr. Linda Brady (DNBBS) at the 
addresses provided under INQUIRIES.

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

Note:  Do NOT submit documents 1-3 above with the application.  However, awards 
will not be made until these documents are received and approved by NIMH 

E.  INTELLECTUAL PROPERTY AND RESEARCH RESOURCE SHARING PLANS

Restricted availability of unique research resources upon which further studies are 
dependent, can impede the advancement of research.  The NIH is interested in 
ensuring that research resources (e.g., biomarkers, clinical endpoints, testing 
batteries, IND filing information for pharmacological agents) developed using funds 
through this RFA become readily available to the broader research community in a 
timely manner for further research, development, and application, in the 
expectation that this will lead to products and knowledge of benefit to the public 
health.  To address this interest in assuring such research resources are 
accessible, NIH requires applicants who respond to this RFA to submit a plan: (1) 
for sharing research resources generated through the grant; and (2) addressing how 
applicant(s) will exercise intellectual property rights, should any be generated 
through this grant, while making such research resources available to the broader 
scientific community consistent with the programmatic goals and objectives of this 
RFA.

The sharing of research resources plan and intellectual property plan must make 
unique research resources readily available for research purposes to qualified 
individuals within the scientific community in accordance with the NIH Grants 
Policy Statement (http://grants.nih.gov/grants/policy/nihgps/) and the Principles 
and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and 
Disseminating Biomedical Research Resources: Final Notice, December 1999 
((http://www.ott.nih.gov/policy/rt_guide_final.html) and 
(http://ott.od.nih.gov/NewPages/64FR72090.pdf) (“NIH Research Tools Policy”)).  
These documents further: (i) define terms, parties, and responsibilities; (ii) 
prescribe the order of disposition of rights; (iii) prescribe a chronology of 
reporting requirements, and (iv) delineate the basis for and extent of government 
actions to retain rights.  Also, patent rights clauses may be found at 37 CFR Part 
401.14 and are accessible from the Interagency Edison web page, 
http://www.iedison.gov or https://s-edison.info.nih.gov/iEdison/.

There should NOT be separate sharing plans for each research component, but rather 
a single plan for the Group as a whole.

In the development of the research resource sharing and intellectual property 
plans, applicants should confer with their own institution’s office(s) responsible 
for handling technology transfer related matters and/or their sponsored research 
office(s).  If applicants or their representatives require additional guidance in 
preparing these plans, they are encouraged to make further inquiries to the 
appropriate contacts listed below.  Further, applicants may wish to independently 
research and review examples of possible approaches considered by other 
institutions.

F.  An NIH intramural scientist may not serve as the Principal Investigator of a 
CDDG but may participate in a Group as a Research 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 and, if applicable, 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 Coordinator as described below in TERMS AND 
CONDITIONS OF AWARD.  For CDDG 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 NIMH Coordinator(s) assigned to the CDDG.  
The tasks and activities are described more fully below.

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

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 for performance and proper conduct of all research supported in the 
CDDG, including the NIH intramural component, if applicable, in accordance with the 
Terms and Conditions of Award. 

b.  The Principal Investigator will establish a Steering Committee consisting of 
the PI, Research Project Leaders, Core Directors, external scientific advisors, and 
the NIMH Coordinator(s).  The Steering Committee members will meet 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 
Steering Committee.  The NIMH Program Official may attend Steering Committee 
meetings as a non-voting participant.  The frequency of meetings, not fewer than 
two per year, will be determined by the PI 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.  

c.  The Awardee Institution and/or Research Project Leader's Institution will 
retain custody of the data, subject to the Government’s right to obtain and use the 
data under 45 CFR 74.36.  The NIMH 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 support, 
including the assigned cooperative agreement award number.

d.  It is the intention that new chemical entities be fully evaluated as potential 
candidate drugs for serious mental disorders, 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 submit to the NIMH for review 
INTELLECTUAL PROPERTY AND PATENT RIGHTS FOR NEW CHEMICAL ENTITIES or the 
INTELLECTUAL PROPERTY AND RESEARCH RESOURCE SHARING PLANS to ensure consistency 
with NIH policy.

3.  NIMH Staff Responsibilities

During performance of the award, the role of the NIMH Coordinator(s) is one of 
substantial involvement above and beyond the normal program stewardship role of a 
Program Officer.  The NIMH Coordinator 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 NIMH Coordinator(s) will be a voting 
member(s) of the Steering Committee, sharing a single vote.  The NIMH Program 
Official may attend Steering Committee meetings as a non-voting participant.  In 
all cases, the role of NIMH will be to assist and facilitate and not to direct 
activities.
 
The NIMH Coordinator(s) can recommend to their institute to utilize their drug 
development resources (e.g., CNS receptor screening, chemical synthesis, and 
toxicology services) in support of the CDDG 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 
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 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

A governing Steering Committee composed of the PI, Research Project Leaders, 
Core Directors, external scientific advisors, and NIMH Coordinator(s) will be 
established in each CDDG to assist in monitoring and development of 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 Principal Investigator who will 
be responsible for scheduling the time and place (generally at one of the 
performance sites) and for preparing concise proceedings or minutes (two or 
three pages) which will be delivered to the members of the Group within 30 
days of the meeting.

a.  The principal end products of CDDG activities are expected to include:  1) 
Human proof-of-concept, early phase II, or other studies such as clinical dose 
optimization, pharmacokinetics, and pharmacodynamics studies to determine with 
reasonable certainty whether a drug candidate is sufficiently safe and effective to 
warrant further clinical and commercial development; 2) research tools, 
instruments, and methods; and 3) pharmacokinetic, pharmacodynamic, and dose 
optimization data related to novel therapeutic candidates.

b.  NIMH 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 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 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 may be brought to arbitration.  An arbitration panel will be composed 
of three members:  one Group designee, one NIMH 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 related to proof-of-
concept studies primarily utilizing clinical endpoints, to:

Wayne S. Fenton, M.D.
Division of Mental Disorders, Behavioral Research and AIDS
National Institute of Mental Health
6001 Executive Boulevard, Room 6216, MSC 9621
Bethesda, MD  20892-9621
Telephone:  (301) 443-9700
Email:  wfenton@mail.nih.gov

o Direct your questions about scientific/research issues related to studies 
primarily focused on pharmacokinetics, pharmacodynamics, dose finding, in-vivo 
receptor occupancy, and those that primarily use putative biomarkers (e.g., 
psychophysiology, imaging) as endpoints, to:

Linda Brady, Ph.D.
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:  lbrady@mail.nih.gov

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:  kozakm@mail.nih.gov

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

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

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 other key personnel 
o 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.  The letter of intent should be sent to:

Wayne S. Fenton, M.D.
Division of Mental Disorders, Behavioral Research and AIDS
National Institute of Mental Health
6001 Executive Boulevard, Room 6216, MSC 9621
Bethesda, MD  20892-9621
Telephone:  (301) 443-9700
Email:  wfenton@mail.nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001). Applications must have a DUN and Bradstreet 
(D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier 
when applying for Federal grants or cooperative agreements. The DUNS number can be 
obtained by calling (866) 705-5711 or through the web site at 
http://www.dunandbradstreet.com/. The DUNS number should be entered on line 11 of 
the face page of the PHS 398 form. The PHS 398 document is available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format.  
For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: 
GrantsInfo@nih.gov.

SUPPLEMENTARY INSTRUCTIONS

1.  SPECIFIC INSTRUCTIONS FOR PREPARING THE CDDG 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.

Applicants should follow the PHS 398 instructions, including: face page (form page 
1); description, performance sites, and key personnel (form page 2); research grant 
table of contents (appropriate to the application’s content); detailed budget of 
overall application for the initial budget period (form page 4); and budget of 
overall application for entire proposed period of support (form page 5).  This 
should be followed by an introductory section of no more than ten pages that 
provides a General Description of the CDDG.  The content requirements of this 
General Description section are described in #3 below.

Following the General Description(s), each component (the Research Projects) should 
be presented individually.  Each project should have the following: a cover page 
stating the Project number, the Project title, and Project PI; a form page 2 which 
includes the description, performance site, and key personnel; individual project 
budget pages (for the initial budget period and for the entire budget period), 
followed by the budget justification; biographical sketches; resources; 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 CDDG.

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 CDDG 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 CDDG as a 
whole.

2.  SPECIFIC INSTRUCTIONS FOR PREPARING THE CDDG 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 RFA.

Applicants should follow the PHS 398 instructions, including: face page (form page 
1); description, performance sites, and key personnel (form page 2); research grant 
table of contents (appropriate to the application’s content); detailed budget of 
overall application for the initial budget period (form page 4); and budget of 
overall application for entire proposed period of support (form page 5).  This 
should be followed by an introductory section of no more than ten pages that 
provides a General Description of the CDDG.  The content requirements of this 
General Description section are described in #3 below.

Following the General Description(s), each component (the Research Projects and 
Cores) should be presented individually.  Each project and core should have the 
following: a cover page stating the Project number or Core letter, the Project or 
Core title, and Project or Core PI; a form page 2 which includes a description, 
performance site, and key personnel; individual project or core budget pages (for 
the initial budget period and for the entire budget period), followed by the budget 
justification; biographical sketches; resources; 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 CDDG.

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 CDDG 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 CDDG 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 
CDDG 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 CDDG

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 CDDG, 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 detailed plan for protection of human subjects must be provided, as must a 
data and safety monitoring plan.

o  A clear description of how each component Research Project is required for the 
attainment of the CDDG'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 documenting and 
disseminating group meeting proceedings.

o  Description of the steps that will be taken to ensure successful completion of 
the CDDG’s research should a key member leave the Group.

4.  SUPPLEMENTARY INSTRUCTIONS FOR NIH INTRAMURAL RESEARCHERS

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

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

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 
and with the PHS policy on vertebrate animal research (if applicable for either).

USING THE RFA LABEL:  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.

SENDING AN APPLICATION TO THE NIH:  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:  jnoronha@mail.nih.gov

APPLICATION PROCESSING:  Applications must be received on or before 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.

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and funding 
assignment within 8 weeks.
 
The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application.  
However, when a previously unfunded application, originally submitted as an 
investigator-initiated application, is to be submitted in response to an RFA, 
it is to be prepared as a NEW application.  That is, the application for the 
RFA must not include an Introduction describing the changes and improvements 
made, and the text must not be marked to indicate the changes from the 
previous unfunded version of the application.

PEER REVIEW PROCESS  

Upon receipt, applications will be reviewed by the CSR for completeness, and by 
NIMH 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  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 written critique
o  Receive a second level review by the National Advisory Mental Health 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 development of new 
pharmacological agents to treat serious mental illness and the development of 
methodological approaches for clinical research.  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 CDDG, as well as 
the CDDG as a whole, will be evaluated.

REVIEW CRITERIA FOR THE CDDG 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 
pharmacological agent with significant potential to reduce the burden of mental 
illness? 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 development of novel 
drugs and research tools 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 CDDG objectives?  Does the applicant acknowledge potential 
problem areas and consider alternative tactics?  Are preclinical models relevant to 
serious mental illness?  If pharmaceutical partnerships are proposed, how will they 
facilitate the development and evaluation of candidate drugs and model validation 
for testing therapeutics?

3.  Innovation.  Does the CDDG employ novel concepts, approaches or methods?  Are 
the aims original and innovative?  Does the CDDG challenge existing paradigms, 
develop new research tools, methodologies, or technologies?  Is the target under 
investigation for drug development novel?  Will new paradigms for drug development 
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 CDDG?  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? Is the research environment adequate for the safe and ethical 
conduct of clinical research ?

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

REVIEW CRITERIA FOR RESEARCH PROJECTS

1.  Significance.  Does this study address an important problem?  If the aims of 
the application are achieved, how will development of the therapeutic approach be 
advanced?  What will be the effect of these studies on the future development of 
putative therapeutic agent or agents with comparable mechanisms.

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 establish preliminary evidence of efficacy in 
human disease adequate ?  If pharmaceutical partnerships are proposed, how will 
they facilitate the further 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? Does the clinical research team demonstrate a track 
record in successfully recruiting human subjects into clinical trials and research 
studies and completing proposed studies within projected timelines? 

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 CDDG.  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 REVIEW CRITERIA:  In addition to the above criteria, the following items 
will be considered in the determination of scientific merit and the priority score:

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human 
subjects and protections from research risk relating to their participation 
in the proposed research will be assessed. (See criteria included in the 
section on Federal Citations, below).
 
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of 
plans to include subjects from both genders, all racial and ethnic groups 
(and subgroups), and children as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects will also be 
evaluated. (See Inclusion Criteria in the sections on Federal Citations, 
below).

ADDITIONAL REVIEW CONSIDERATIONS

SHARING AND INTELLECTUAL PROPERTY PLANS:  The adequacy of the sharing and 
intellectual property plans in effectively making research resources generated 
under the project widely available to the scientific community, while providing for 
the further research and development of new pharmacological treatments for serious 
mental illness consistent with the programmatic goals and objectives of this RFA.

BUDGET:  The reasonableness of the proposed budget and duration, as presented in 
the individual Research Projects, Cores, as well as the overall CDDG budget, in 
relation to the proposed research.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:    July 23, 2004
Application Receipt Date:         August 25, 2004
Peer Review Date:                 November 2004
Council Review:                   January 2005
Earliest Anticipated Start Date:  February 1, 2005

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

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).  The establishment of data and safety monitoring boards (DSMBs) 
is required for multi-site clinical trials involving interventions that entail 
potential risk to the participants.   (NIH Policy for Data and Safety Monitoring, 
NIH Guide for Grants and Contracts, June 12, 1998: 
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, 
local IRB rules, as well as local, state and Federal laws and regulations, 
including the Privacy Rule. Reviewers will consider the data sharing plan but will 
not factor the plan into the determination of the scientific merit or the priority 
score.

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of 
the NIH that women and members of minority groups and their sub-populations 
must be included in all NIH-supported clinical research projects unless a 
clear and compelling justification is provided indicating that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of 
the research. This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43).

All investigators proposing clinical research should read the "NIH Guidelines 
for Inclusion of Women and Minorities as Subjects in Clinical Research - 
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 are 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 RESEARCH INVOLVING HUMAN SUBJECTS: The NIH 
maintains a policy 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. 

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 is available at 
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 proposals for research involving human 
subjects.  You will find this policy announcement in the NIH Guide for Grants 
and Contracts Announcement, dated June 5, 2000, at 
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.

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.  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 at http://www.cfda.gov/ and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health Systems 
Agency review.  Awards are made under 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.  
All awards are subject to the terms and conditions, cost principles, and other 
considerations described in the NIH Grants Policy Statement available at 
http://grants.nih.gov/grants/policy/policy.htm.

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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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