CENTER FOR COLLABORATIVE GENETIC STUDIES ON MENTAL DISORDERS

RELEASE DATE:  March 28, 2002

RFA:  MH-03-003

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

PRE-APPLICATION MEETING:  May 15, 2002
LETTER OF INTENT RECEIPT DATE:  September 16, 2002
APPLICATION RECEIPT DATE:  October 16, 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 OF THIS RFA

The National Institute of Mental Health (NIMH) invites applications for 
support of a Center for Collaborative Genetic Studies on Mental Disorders, 
which will contribute to the improvement and enrichment of research resources 
to be distributed for genetic studies of mental disorders under the rubric of 
the NIMH Human Genetics Initiative (http://zork.wustl.edu/nimh/NIMH
_initiative/NIMH_initiative_link.html).  The Center, which will function
as a integrated team of investigators with expertise in molecular biology,
statistical genetics, bioinformatics and psychiatric genetics within a single
institution or across institutions, will facilitate and accelerate free and
open sharing among researchers in the scientific community by providing on a
fee-for-service basis:  DNA, cell lines, electronic data files, and services
for the genetic analysis of mental disorders.

The goal of this initiative will be to enrich and distribute clinical 
information, genotypic data, DNA samples, and cell lines from large numbers 
of unrelated affected individuals and from pedigrees of affected individuals 
and their relatives.  Such research resources will provide adequate 
statistical power for discovering genes that produce vulnerability to mental 
disorders.  Data and biomaterials collected and produced by the Center will 
augment pre-existing resources in the NIMH Human Genetics Initiative for 
genetic analyses by the wider scientific community.

RESEARCH OBJECTIVES

Background

The free and open sharing of genetic material and clinical data among 
researchers has been essential in accelerating discoveries in human genetics. 
A recent national survey of life scientists found that over 70% of 
geneticists felt that lack of data sharing detracted from the level of 
communication in science and slowed the rate of progress in their field; the 
major conclusion was that the impact of data withholding in academic genetics 
is widespread and adversely affects essential scientific activities such as 
the ability to confirm published results.  For mental disorders and other 
genetically complex diseases in which gene effects are modest, sharing is 
often absolutely necessary to achieve sample sizes that have adequate 
statistical power for gene mapping.  Other specific scientific advantages of 
sharing research resources include facilitating the rapid replication of new 
findings, stimulating multidisciplinary research among clinical and basic 
scientists, providing needed clinical resources to promising young 
investigators, avoiding duplicative data collection efforts and laboratory 
work, and facilitating the rapid application of state-of-the-art genomic 
technologies and analytic methods to clinical data sets.  These advantages 
are expected to facilitate our understanding of disease pathophysiology, and 
accelerate the development of new therapeutic compounds and diagnostic tests.

In the late 1980s, NIMH launched a Human Genetics Initiative
(http://zork.wustl.edu/nimh/NIMH_initiative/NIMH_initiative_link.html)
to study the genetic basis of vulnerability to schizophrenia, Alzheimer's
disease, and bipolar disorder.  The main goal of this effort was to accelerate
gene discovery through the sharing of electronic databases of clinical
information, DNA samples, and cell lines as a national resource for the
scientific community.  In 1997, a workgroup of the National Advisory Mental
Health Council reviewed the NIMH genetics research portfolio and recommended
that NIMH continue to fund large-scale data collection efforts and to
maintain a repository of DNA and clinical data for sharing with the scientific
community (see the report summary at http://www.nimh.nih.gov/research/
genetics.htm).  The Workgroup also discussed future expansion of these
efforts to include other mental disorders.  At a joint meeting in September
2000, the National Advisory Councils of the NIMH and the National Institute
of Neurological Disorders and Stroke strongly recommended that data sharing
for the genetic analysis of complex diseases supported by these Institutes
continue to be strongly encouraged.

In order to enhance and enrich research resources in the NIMH Human Genetics 
Initiative for free and open sharing with the scientific community, the NIMH 
plans to fund one Center under this RFA.  An example of the benefits of data 
sharing expected from Center activities is the recent successful effort to 
promote collaboration across investigators involved in the collection of 
families with Crohn disease.  Whereas individual data sets reporting linkage 
to three different chromosomes did not have sufficient power alone to yield 
conclusive evidence, pooling the data from investigators in 13 countries 
provided unequivocal replication of linkage for Crohn disease to a marker on 
chromosome 16.

The long-term objective of data sharing and research resource enrichment 
under this RFA is to accelerate gene discovery in mental disorders that 
include Alzheimer's disease, attention-deficit hyperactivity disorder, autism 
and related spectrum disorders, bipolar disorder and other related mood 
disorders, recurrent early-onset depression, eating disorders, obsessive-
compulsive disorder and other anxiety disorders, panic disorder, 
schizophrenia, and other psychotic disorders.

Research Objectives

The NIMH will utilize the U24 Resource-Related Research Projects   
Cooperative Agreements funding mechanism to establish one Center for 
Collaborative Genetic Studies on Mental Disorders to serve as a national and 
international resource to the scientific community.  The Center funded under 
this RFA will be directed by a Principal Investigator (PI) and will receive 
guidance from NIMH program staff to assist with identification and 
implementation of appropriate strategies and priorities.  It is expected that 
the Center will be comprised of an integrated team of investigators (within a 
single institution or across institutions) with expertise in molecular 
biology, statistical genetics, bioinformatics and psychiatric genetics.  
Regardless of how many institutions are involved, it is expected that the 
efforts of the Center will be strategically and functionally coordinated such 
that the Center will function as a single, national resource.  It is expected 
that the principal investigator and the proposed collaborative team have 
direct experience in providing to the scientific community research resources 
and services for genetic studies.  Specific areas of scientific expertise 
required by the Center include the following:

o  Molecular biology, with a primary focus on the Epstein-Barr virus 
transformation of lymphocytes from fresh blood samples received from national 
and international sites to create contaminant-free cell lines, and the 
extraction of high-quality DNA from these cell lines.

o  Bioinformatics, with a primary focus on the receipt and production of 
pedigree, clinical (including information obtained from structured 
psychiatric interviews), genotypic and other genetic data for the 
establishment of documented web-based data files for the genetic analysis of 
mental disorders.  This work will also encompass the development and 
application of novel technological or computational methods for the 
production and analysis of comprehensive genomic data sets.

o  Statistical genetics of complex diseases, with a primary focus on the 
development of algorithms and well-documented software for meta-analytic 
genetic studies and clustering and other classification techniques in genetic 
analysis.  This work will also encompass the development of novel statistical 
approaches by which linkage findings from multiple genomic scans may be 
jointly analyzed to fine map disease susceptibility loci.

o  Analysis of psychiatric family data, with a primary focus on the 
development of analytic methods by which psychiatric diagnostic information 
can be analyzed to identify biologically meaningful phenotypes and clinical 
subtypes.

Coordination of the Center's activities will be accomplished through close 
collaboration between the Center scientific staff, NIMH program staff, and a 
scientific steering committee (Genetics Steering Committee (GSC)).  A 
Genetics Advisory Panel (GAP), composed of experts not affiliated with the 
Centers or the GSC, also will be formed to provide scientific oversight of 
the Center and to address long-term strategic issues and policies related to 
the gene discovery and characterization of the genetic basis of mental 
disorders.  GSC, GAP, PI, and NIMH responsibilities are described under 
SPECIAL REQUIREMENTS.

Specific functions and services to be performed by the Center for the 
scientific community include: 

o  Resolution of the discrepancies in linkage findings obtained in multiple 
data sets for mental disorders.

o  Exploration of explanations for discrepancies - either at the level of the 
phenotype definition, characterization of DNA markers, or statistical methods 
- which would provide a stronger base for a priori testing of particular 
candidate regions in future genetic studies.

o  Development of analytic approaches for the pooling of data on therapeutic 
drug response, in order to accelerate gene discovery.

o  Development of novel statistical approaches by which linkage findings from 
multiple genomic scans may be jointly analyzed to fine map disease 
susceptibility loci.

o  Receipt from national and international research projects supported under 
the NIMH Human Genetics Initiative of blood samples for cell line 
immortalization and of clinical and genetic data files.  This includes blood 
samples drawn from unrelated affected individuals in NIMH-supported large-
scale clinical trials.

o  Creation and maintenance of contaminant-free lymphoblastoid cell lines, 
immortalized from fresh whole blood samples with a success rate of greater 
than 98% (for samples shipped from both domestic and foreign sites), and 
extraction of high-quality DNA.

o  Verification of sample identity, gender, and pedigree relationships on 
blood samples received from research projects supported under the NIMH Human 
Genetics Initiative.

o  Distribution of datafiles and biomaterials (cell lines and DNA) to the 
scientific community, according to the unique needs of investigators.

o  Consultation on the experimental design of pharmacogenomic and other 
genetic studies, and development of analytic methods by which clinical and 
genotypic data may be pooled for meta-analytic genetic studies of mental 
disorders.

o  Provision of algorithms and well-documented software for meta-analytic 
studies of genotypic data, and consultation on applying clustering and other 
classification techniques in genetic analysis.

o  Consultation on the analysis of psychiatric family study data obtained 
from diagnostic interviews.

o  Establishment and distribution of pedigree datasets, in which non-
Mendelian inheritances and other errors determined from genome scans and 
other genetic analyses are resolved.

o  Receipt, production and distribution of databases of genotypic information 
received from multiple laboratories, in which genotyping inconsistencies are 
reconciled.

o  Provision of novel technological or computational methods for the 
production and analysis of comprehensive genomic data sets.

These services and research resources will be provided to the scientific 
community by the Center on a fee-for-service basis.  Fees charged will 
recover costs and service delivery costs.  Applications in response to this 
RFA should include detailed plans for the advisory, research and development, 
and other fee-for-service functions of the Center.

MECHANISM OF SUPPORT

This RFA will use the NIH Resource-Related Research Projects   Cooperative 
Agreements award mechanism (U24).  As an applicant, you will be solely 
responsible for planning, directing, and executing the proposed project.  
This RFA is a one-time solicitation.  The earliest anticipated award date is 
July 1, 2003.

The NIH U24 is a cooperative agreement award mechanism 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."

FUNDS AVAILABLE

The NIMH intends to commit approximately $4.7 million in FY 2003 to fund one 
new cooperative agreement in response to this RFA.  An applicant may request 
a project period of up to 5 years.  Although the financial plans of the NIMH 
provide support for this program, awards pursuant to this RFA are contingent 
upon the availability of funds and the receipt of a sufficiently meritorious 
application.  At this time, it is not known if this RFA will be reissued.

ELIGIBLE INSTITUTIONS

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

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

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 their institution to 
develop an application for support.  Individuals from underrepresented racial 
and ethnic groups as well as individuals with disabilities are always 
encouraged to apply for NIH programs.

SPECIAL REQUIREMENTS

I.  Definitions

ARBITRATION PANEL:  A panel that would be formed to arbitrate scientific or 
programmatic disagreement, should any arise, between award recipients and the 
NIMH within the scope of the award.

AWARDEE:  The institution to which a cooperative agreement is awarded.

COOPERATIVE AGREEMENT:  An assistance mechanism in which there is anticipated 
substantial NIMH programmatic involvement with the recipient organization 
during the performance of the planned activity.

PRINCIPAL INVESTIGATOR (PI):  The researcher who assembles the project, 
submits an application in response to this RFA, and assumes responsibility 
for the overall performance of the project.  The PI will coordinate project 
activities scientifically and administratively.

NIH PROGRAM DIRECTOR:  A scientist of the NIMH program staff who has 
substantial scientific/programming involvement.

GENETICS STEERING COMMITTEE (GSC):  The main governing board of the Center 
funded under this RFA, through which the NIMH formally interacts with the 
Center.  Membership includes the NIMH Program Director, the PI, and two 
extramural scientists with relevant expertise who are not affiliated with the 
funded project.

GENETICS ADVISORY PANEL (GAP):  A panel of extramural researchers who provide 
scientific oversight of the Center.  GAP evaluates the goals and objectives 
of the NIMH Human Genetics Initiative, the progress of the Center in relation 
to the ongoing needs of the scientific community in genetic studies of mental 
disorders, and the inclusion of state-of-the-art genomic tools and 
technologies in Center activities.

II.  Pre-Application Meeting

Prospective applicants are invited to attend a pre-application meeting on May 
15, 2002, at the NIMH in Rockville, MD.  This meeting will provide the 
opportunity for NIH staff to clarify any requirements of the RFA.  At the 
pre-application meeting, NIH staff will explain the purpose of this RFA, 
provide detailed instructions about the application process, and answer 
questions.  Interested scientists should contact the NIMH program staff 
contact listed under WHERE TO SEND INQUIRIES to obtain further information.  
Potential applicant institutions are urged to send a representative to this 
meeting.  Anyone who cannot attend this meeting will be provided with any 
distributed materials and with a summary of the discussion within two weeks 
of the meeting.

III.  Program Income

Fees charged by the Center will constitute Program Income.  Program Income is 
gross income earned by the awardee that is directly generated by a supported 
activity or earned as a result of the award (see 45 CFR 74.2 and 74.24 for 
additional information).  An estimate of the amount and source of Program 
Income that will be generated as a result of the award must be included on 
the Checklist Page of all competing and non-competing continuation 
applications.  Net program income earned during a budget period must be 
reported on the annual Financial Status Report (FSR) (except for Program 
Income earned as a result of inventions, to which special rules apply).  
Costs incident to the generation of Program Income may be deducted from gross 
income to determine Program Income to be reported on the FSR, provided that 
these costs have not been charged to the award.

Program Income earned during the project period shall be retained by the 
award recipient and is to be deducted from the total project or program 
allowable costs in determining the net allowable costs on which the federal 
share of costs is based.  The NIMH may offset a future award by this amount 
or reauthorize it for expenditure on a future award.

IV.  Quarterly Meetings

The GSC will meet quarterly at the NIMH.  Applications in response to this 
RFA should include a request for funds to cover the expense of attending 
these meetings in Rockville, MD.

V.  Data Sharing

The sharing of biomaterials, data, and software in a timely manner has been 
an essential element in the rapid progress that has been made in the genetic 
analysis of human diseases.  NIH policy requires that investigators make 
unique research resources produced with DHHS funding available for research 
purposes to qualified individuals within the scientific community (NIH Grants 
Policy Statement - March 2001, Part II Subpart A, Availability of Research 
Results: Publications, Intellectual Property Rights, and Sharing Biomedical 
Research Resources, page 120-122, "Sharing Biomedical Research Resources," 
available at 
http://grants.nih.gov/grants/policy/nihgps_2001/nihgps_2001.pdf); see also 
PHS policy relating to the distribution of unique research resources produced 
with PHS funding at http://grants.nih.gov/grants/guide/notice-files/not96-
184.html).  Principles and guidelines for sharing biomedical research 
resources also can be found in online NIH reports at 
http://www.nih.gov/science/models/sharing.html and 
http://www.nih.gov/news/researchtools/index.htm.  A draft NIH Statement on 
sharing research data that extends these policies has recently been published 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-035.html.  
Providing access to data collected in human genetic studies for qualified 
investigators in the wider scientific community has been a guiding principle 
of the NIMH Human Genetics Initiative (http://zork.wustl.edu/nimh/
NIMH_initiative/NIMH_initiative_link.html).

To address the joint interests of the government in the availability of, and 
access to, the results of publicly funded research and in the opportunity for 
economic development based on these results, the NIMH requires applicants who 
respond to this RFA to develop and propose detailed plans for sharing and 
disseminating the data and biomaterials produced and received through the 
Center.  It is expected that the information to be shared includes clinical, 
diagnostic, and pedigree structure information, in addition to cell lines and 
DNA.  Policies and procedures in the NIMH Human Genetics Initiative specify 
that DNA, cell lines, and datafiles be widely accessible by investigators in 
the scientific community.  The NIMH Human Genetics Initiative employs 
procedures by which data and biomaterials are widely disseminated to 
qualified investigators in the scientific community
(http://zork.wustl.edu/nimh/NIMH_initiative/NIMH%20Human%20Genetics%20
Initiative%20Access%20Information.htm).  It is preferable that the
procedures for sharing data and biomaterials are comparable to those
currently employed in the NIMH Human Genetics Initiative.

It is expected that the investigator's data sharing plan will specify the 
following elements: (1) the production of comprehensive and verified 
databases that contain clinical, diagnostic, pedigree structure, and 
genotypic information collected and produced by the Center; (2) the 
establishment of cell lines, from which DNA will be extracted and stored, for 
all subjects studied from whom blood samples have been received by the 
Center; (3) mechanisms by which all databases and biomaterials (DNA samples, 
cell lines) are widely distributed to qualified investigators in the 
scientific community; (4) a protocol and criteria for free and open sharing 
of these data and biomaterials; and (5) an assurance that data and 
biomaterials are shared in a manner comparable to pre-existing protocols and 
procedures for sharing such research resources in the NIMH Human Genetics 
Initiative.  

The Scientific Review Group will comment on the proposed plan for sharing and 
data access.  The plan will be considered as an important part of the 
methodology for carrying out the research and, as such, the adequacy of the 
plan will be considered by NIMH staff in determining whether the grant shall 
be awarded.  The sharing plan as approved, after negotiation with the 
applicant when necessary, will be a condition of the award.

VI.  Cooperative Agreement Terms and Conditions of Award

The following special Terms and Conditions will be incorporated into the 
cooperative agreement award statement and are in addition to, and not in lieu 
of, otherwise applicable OMB administrative guidelines, HHS grant 
administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable 
when State and local Governments are eligible to apply), and other HHS and 
NIH grant administration policies:

The administrative and funding instrument used for this program will be the 
U24, an "assistance" mechanism (rather than an "acquisition" mechanism), in 
which substantial NIH scientific and/or programmatic involvement with the 
awardees is anticipated during performance of the activities.  Under the 
cooperative agreement, the NIH purpose is to support and/or stimulate the 
recipient's activities by involvement in and otherwise working jointly with 
the award recipients in a partnership role.  The NIH purpose is not to assume 
direction, prime responsibility, or a dominant role in the activities.  
Consistent with this concept, the dominant role and prime responsibility 
resides with the awardee for the project as a whole, although specific tasks 
and activities will be shared among the awardee, GSC, and NIMH program staff.

1.  Awardee Rights and Responsibilities

The awardee, as Center PI, will coordinate project activities scientifically 
and administratively at the awardee institution, and will have primary 
responsibility for performing all scientific and fee-for-service activities.  
The Center PI must agree to participate with NIMH program staff and GSC in 
coordinating the activities of the Center, with the result that all 
investigators included in the application function as a single functioning 
Center.  The PI agrees to accept the close coordination, cooperation, and 
participation of the Program Director, GSC, and GAP in those aspects of 
scientific and technical management of the project as described below.  
Specifically, the PI will:

o  Determine experimental approaches, design protocols, oversee the provision 
of services and research resources to the scientific community, and work 
cooperatively to set project milestones, in consultation with NIMH program 
staff, GSC, and GAP.

o  Distribute biomaterials and datafiles for researchers granted access by 
the NIMH to research resources in the NIMH Human Genetics Initiative.  Access 
determinations will be made by the NIMH with input as required from GAP.

o  Maintain a log of Center usage that records the products and services 
provided and the fees charged.

o  Prior to each non-competing renewal, submit progress reports in a standard 
format, as agreed upon by GSC.  The progress report will describe the 
activities and accomplishments of the Center for the preceding award period, 
and the goals to be accomplished during the renewal period.  The progress 
report will include the log of Center usage.  The contents of the progress 
report will be used by NIMH program staff, along with other information, to 
determine the amount of funding the Center will receive for the renewal 
period.

o  Accept and implement the common guidelines and procedures approved by GSC 
and GAP.

o  Attend and participate in GSC meetings (budget requests should include 
travel funds for the PI and other critical staff to attend GSC meetings at 
the NIMH in Rockville, MD, on a quarterly basis).  The awardee will have one 
vote on GSC and will accept any modification, deletion, or addition of Center 
activities approved by GSC.

2.  NIMH Program Staff Responsibilities

The NIMH Program Director will have substantial scientific/ programmatic 
involvement during the conduct of this activity through technical assistance, 
advice, and coordination.  This includes functioning as a peer with the PIs, 
facilitating the partnership relationship between the NIMH and the Center, 
helping to maintain the overall scientific balance in the program 
commensurate with new research and emerging research opportunities, and 
ensuring that the activities of the Center are consistent with the scientific 
mission of the NIMH Human Genetics Initiative
(http://zork.wustl.edu/nimh/NIMH_initiative/NIMH%20Human%20Genetics%20
Initiative%20Mission.htm).  The role of the NIMH will be to facilitate 
and not to direct activities.  Access to research resources maintained in the 
NIMH Human Genetics Initiative will be determined by NIMH staff, with input 
as required from GAP.  The NIMH Program Director shall participate as a 
member of GSC and will have one vote.  Specifically, the NIMH Program 
Director will:

o  Provide relevant scientific expertise and overall knowledge.

o  Recruit and select the members of GSC, who will each serve a three-year 
term.  The Program Director will also have the responsibility of replacing 
GAP or GSC members that choose to leave.  The Program Director may, but is 
not required to, consult with Center PIs, GSC members, GAP members, or other 
outside advisors when recruiting GSC and GAP members.

o  Attend GSC meetings as one voting member and assist in developing 
operating guidelines, quality control procedures, and consistent policies for 
dealing with recurrent situations that require coordinated action.  The 
Program Director must be informed of all major interactions of members of 
GSC.  The Program Director will be responsible for preparing within 30 days a 
concise summary of each GSC meeting.

o  Participate with other GSC members in the group process of setting 
research priorities and milestones, deciding optimal research approaches and 
protocol designs, and contributing to the adjustment of research protocols or 
approaches as warranted.  The Program Director will assist and facilitate the 
group process and not direct it.

o  Serve as administrative liaison to GAP, attending GAP meetings as a non-
voting member, to help coordinate Center activities with the development of 
evolving tools and technologies in genomic and genetic science.  The Program 
Director will also coordinate Center activities with the scientific mission 
and evolving goals of the Human Genetics Initiative, with input as required 
from GAP.  The Program Director will also coordinate Center activities with 
other US and international efforts that focus on sharing research resources 
for genetic analyses of complex diseases.

o  Appoint the GSC and GAP Chairs, based on recommendations from GSC and GAP 
members.

o  Serve as scientific liaison between the Center and other NIH staff.

o  Assist in promoting and encouraging the sharing of unique research 
resources for genetic studies of mental disorders by the scientific community 
at large.

o  Develop timetables for the timely, open, and free sharing of research 
resources received and produced by the Center to the scientific community.

o  Coordinate Center activities to ensure the efficient long-term storage of 
research resources.
 
o  Retain the option to recommend re-allocating NIMH support provided to the 
Center, as scientific goals evolve.

o  Determine the amount of support that will be awarded to the Center as a 
non-competing renewal.  The progress report received from each Center, along 
with other information, will be used to make this determination.  The 
criteria used for this decision will include, but not be limited to, Center 
production, customer satisfaction, and successful performance of the Center 
as a member of the consortium.

3.  Collaborative Responsibilities - Genetics Steering Committee (GSC)

All collaborative activities of the awardee and NIMH staff will occur through 
the activities of GSC, which will serve as the governing board of the Center.  
The NIMH will formally interact and collaborate with the Center through GSC, 
which will include the PI, the NIMH Program Director, and two researchers 
(advisors) with relevant scientific expertise who are not affiliated with the 
Center.  These advisors will be appointed by the NIMH Program Director.  One 
of the two advisors will be appointed by the Program Director to be GSC's 
chair, after consideration of recommendations made by GSC.  After appointment 
by the Program Director, the GSC Chair will be responsible for developing 
meeting agendas and chairing meetings.  GSC will meet quarterly.  Additional 
GSC members may be added by action of GSC or GAP.  Other NIH staff may attend 
GSC meetings, when their expertise is required for specific discussions.  The 
Program Director, PI, and each advisor will have one vote each.  In cases 
where members do not agree, any member may ask the chairperson to solicit a 
vote.  In order for a decision or course of action to be finalized by GSC, a 
majority of the possible votes must be cast in favor of the decision or 
course of action.

The GSC will coordinate the activities of the Center and the distribution of 
data, biomaterials, and services to the wider scientific community.  GSC will 
discuss scientific progress, make recommendations regarding the enhancement 
of research resources and facilitation of free and open sharing.  GAP 
recommendations will be addressed by GSC.  The awardee will be required to 
accept and implement the common protocol and procedures approved by GSC.

4.  Scientific Oversight - Genetics Advisory Panel (GAP)

The GAP will meet at least once each year and will oversee Center activities 
to assure that the needs of the broader scientific community for research 
resources necessary for the genetic analysis of mental disorders are being 
met.  GAP will provide oversight of the Center, and scientific advice to GSC 
and NIMH.  GAP members will provide scientific and operational oversight 
concerning both long-term developments and distribution activities at the 
Center.  GAP also will consult on the incorporation of emerging genomic and 
genetic tools and technologies into Center activities.

The GAP will consist of about 10 scientists (advisors) who are not affiliated 
with the Center, and who are not members of any advisory committee of the 
Center.  GAP members will be appointed by the NIMH Program Director and will 
be selected for their broad expertise in relevant topics such as molecular 
biology, molecular genetics, genomics, pharmacogenomics, statistical 
genetics, bioinformatics and psychiatric genetics.  The NIMH will select one 
member to be GAP's chair, after considering GAP recommendations.  Additional 
GAP members may be added by an action of GAP.  The NIMH Program Director will 
attend GAP meetings as a non-voting member and will act as a representative 
of GSC.  Other NIH staff and GSC members may attend GAP meetings, when their 
expertise is required for specific discussions.  GAP members will not vote on 
GSC but may be invited to attend GSC meetings if attendance would 
significantly facilitate GSC business.

Periodically, at intervals determined by GSC, a formal request for advice on 
specific subjects will be submitted to GAP.  The GAP will convene to consider 
and formulate opinions on the questions submitted to it.  NIMH program staff 
will consider GAP opinions with regard to overall Center functioning and when 
making determinations for renewal funding.

5.  Arbitration

Any disagreement that may arise on scientific/programmatic matters (within 
the scope of the award), between award recipients and the NIMH may be brought 
to arbitration.  An arbitration panel will be composed of three members   one 
chosen by GSC (with NIMH not voting) or by the awardee in the event of an 
individual disagreement, a second member selected by the NIMH, and the third 
member with expertise in the relevant area who is selected by the two prior 
selected members.  This special arbitration procedure in no way affects the 
awardee's right to appeal an adverse action that is otherwise appealable in 
accordance with the PHS regulations at 42 CFR Part 50, Subpart D and HHS 
regulation at 45 CFR Part 16.

6.  Milestones and Evaluations

Applicants should define yearly milestones in their applications, and the 
selected awardee will have the opportunity to modify these milestones at the 
time of award.  The awardee's milestones will be reviewed by GSC and GAP.  It 
is expected that the milestones should be adjusted annually at the award 
anniversary dates, both to incorporate a group's scientific accomplishments 
and progress in the field in general, as well as to reflect GSC and GAP 
recommendations.  Following the evaluation of milestones, NIMH program staff 
may recommend augmenting any activity or reducing or withholding funds for an 
activity that substantially fails to meet its milestones or to remain state-
of-the-art.  Augmentation of funds must be in the scope of work of the 
Center's activities and subject to approval by the NIMH and the National 
Advisory Mental Health Council.

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 questions about scientific/research issues to:

Steven O. Moldin, Ph.D.
Genetics Research Branch
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
6001 Executive Boulevard, Room 7189, MSC 9643
Bethesda, MD  20892-9643
Telephone:  (301) 443-2037
FAX:  (301) 443-9890
Email:  [email protected]

o  Direct questions about peer review issues to:

Camilla Day, Ph.D.
Chief, Genetic Sciences IRG
Center for Scientific Review
6701 Rockledge Drive, Room 2212, MSC 7890
Bethesda, MD  20892-7890
Telephone:  (301) 435-1037
FAX:  (301) 480-2067
Email:  [email protected]

o  Direct questions about financial or grants management matters to:

Carol J. Robinson
Grants Management Branch
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6118, MSC 9605
Bethesda, MD  20892-9605
Telephone:  (301) 443-3858
FAX:  (301) 443-6885
Email:  [email protected]

LETTER OF INTENT

Prospective applicants are asked 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 NIMH 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:

Steven O. Moldin, Ph.D.
Genetics Research Branch
Division of Neuroscience & Basic Behavioral Science
National Institute of Mental Health
6001 Executive Boulevard, Room 7189, MSC 9643
Bethesda, MD  20892-9643
Telephone:  (301) 443-2037
FAX:  (301) 443-9890
Email:  [email protected]

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 is 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].

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 NIH:  Submit a signed, typewritten original of the 
application, including the Checklist, and five 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)

APPLICATION PROCESSING:  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.

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.  CSR 
will not accept any application that is essentially the same as one already 
reviewed.  This does not preclude the submission of substantial revisions of 
applications already reviewed, but such applications must include an 
Introduction addressing the previous critique.

PEER REVIEW PROCESS

Upon receipt, applications will be reviewed for completeness by CSR and 
responsiveness by NIMH.  Incomplete and/or non-responsive applications will 
be returned to the applicant without further consideration.  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 CSR 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 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.  In 
the written comments, reviewers will be asked to discuss the following 
aspects of your application in order to judge the likelihood that the 
proposed research will have a substantial impact on the pursuit of these 
goals:

o  Significance 
o  Approach
o  Innovation
o  Investigator
o  Environment

The scientific review group will address and consider each of these criteria 
in assigning your application's overall score, weighting them as appropriate 
for each application.  Your application does not need to be strong in all 
categories to be judged likely to have major scientific impact and thus 
deserve a high priority score.  For example, you may propose to carry out 
important work that by its nature is not innovative but is essential to move 
a field forward.

(1) SIGNIFICANCE:  If the aims of the application are achieved and research 
resources for genetics studies are freely shared with the scientific 
community, how will knowledge on the genetic basis of mental disorders be 
advanced?  What will be the effect of these research resources on other 
scientific activities that drive this field?

(2) APPROACH:  Are the conceptual framework, design, and methods to be used 
for the receipt and sharing of research resources and provision of services 
to the scientific community adequately developed, well-integrated, and 
appropriate?  Will the meta-analytic methods to be developed, and the 
statistical genetic services to be provided, succeed in accelerating the 
discovery of genes producing vulnerability to mental disorders? Does the 
applicant utilize state-of-the-art methods to create efficient web-based 
databases of clinical and genotypic data? Does the investigator utilize 
appropriate molecular biological techniques to assure a high rate of success 
(98% or greater) in establishing cell lines from both domestic and foreign 
sites?

(3) INNOVATION:  Does the project employ novel concepts, approaches, or 
methods for the production and sharing of research resources, for the 
development of analytic methods for meta-analytic studies, and for resolution 
of the discrepancies in linkage findings obtained in multiple data sets for 
mental disorders?  Does the project employ novel methods by which linkage 
findings from multiple genomic scans may be jointly analyzed to fine map 
disease susceptibility loci?

(4) INVESTIGATOR:  Is the investigator appropriately trained and well-suited 
to carry out this work?  Is the work proposed appropriate to the experience 
level of the principal investigator and other researchers (if any)? Does the 
principal investigator have demonstrated experience in providing high-quality 
research resources and services for genetic studies on mental disorders to 
the scientific community? Is the principal investigator highly committed to 
the principals of free and open sharing of research resources for genetic 
studies of mental disorders?

(5) ENVIRONMENT:  Does the 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 scientific environment or employ useful 
collaborative arrangements?  Is there evidence of institutional support?

ADDITIONAL REVIEW CRITERIA:  In addition to the above criteria, your 
application will also be reviewed with respect to the following:

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

o  INCLUSION:  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 
included in the section on Federal Citations, below)

o  DATA SHARING:  The adequacy of the proposed plan to share data, and to 
provide research resources and scientific services to the community.

o  BUDGET:  The reasonableness of the proposed budget and the requested 
period of support in relation to the proposed research.

o  OTHER REVIEW CRITERIA:  The adequacy of the proposed fee-for-service plan, 
including administration and funds management.

RECEIPT AND REVIEW SCHEDULE 

Pre-Application Meeting:        May 15, 2002
Letter of Intent Receipt Date:  September 16, 2002
Application Receipt Date:       October 16, 2002
Peer Review Date:               February/March 2003
Council Review:                 May 2003
Early Anticipated Start Date:   July 1, 2003

AWARD CRITERIA

Criteria that will be used to make award decisions include:

o  Scientific merit, as determined by peer review
o  Availability of funds
o  Programmatic priorities and program balance
o  Commitment to the long-term scientific mission, goals, and objectives of 
the NIMH Human Genetics Initiative

REQUIRED FEDERAL CITATIONS

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 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 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.  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 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.

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.  Furthermore, 
we caution reviewers that their anonymity may be compromised when they 
directly access an Internet site.

HEALTHY PEOPLE 2010:  The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of "Healthy 
People 2010," a PHS-led national activity for setting priority areas.  This 
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, 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 described at 
http://grants.nih.gov/grants/policy/policy.htm and under Federal Regulations 
42 CFR 52 and 45 CFR Parts 74 and 92.

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

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