COLLABORATIVE R01s FOR CLINICAL STUDIES OF MENTAL DISORDERS

NIH GUIDE, Volume 26, Number 40, December 19, 1997

PA NUMBER:  PAR-98-017 (see Update PA-01-123)

P.T.

National Institute of Mental Health

PURPOSE

The National Institute of Mental Health (NIMH) invites applications for
collaborative research efforts on Clinical Studies of Mental Disorders (CSMD)
including schizophrenia, mood disorders, anxiety disorders, and other severe
mental illnesses (see Research Topics below).  This program announcement
provides guidelines for the conceptualization, preparation, review, and
administration of collaborative CSMD applications submitted to the NIMH.

Collaborative CSMD grants support research on a highly related topic at two or
more sites.  The work may involve either identical protocols at multiple
sites, or the sites may have different roles in investigating a common topic
(see examples below).  The purpose of collaborative CSMD is to facilitate
research that requires integration/interaction among organizationally distinct
entities.  It ensures that there will be a Principal Investigator (PI) at each
site, as well as a way for the PIs to make decisions and coordinate efforts
across sites.  This would assure quality control, cross-site training and/or
reliability monitoring, and allow pooling of data for analyses.

Although the investigators as a group must request advance permission from
NIMH to submit such applications if the overall total annual funding requested
will exceed $500K in any year, there is no Government involvement in the
conceptualization, data collection or publication of results.  This makes it
different from a Cooperative Agreement (U01 or U10) application in which the
Government is considered an integral part of the research team.

As a rule, all components of a collaborative CSMD would be reviewed by the
same NIMH Scientific Review Group (SRG) and funded by one NIMH program.  The
collaborative CSMD sites would be interactive, either by undertaking
complementary scientific roles, or by working on a common protocol.  While the
collaborative CSMD is appropriate for studies at different sites of a multi-
campus institution, it is not appropriate for collaborations within a single
campus institution.  Such collaborations within a single campus institution
should consider using the Program Project (P01) mechanism.  Because of the
complexity inherent in most collaborative CSMD applications, and the
additional review criteria related to their administration, applicants are
strongly encouraged to consult with NIMH program staff (listed under
INQUIRIES).

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health promotion
and disease prevention objectives of "Healthy People 2000," a PHS-led national
activity for setting priority areas.  This PAR, Collaborative R01s for
Clinical Studies of Mental Disorders, is related to the priority area of
mental health and mental disorders. Potential applicants may obtain a copy of
"Healthy People 2000" (Full Report:  Stock No. 017-001-00474-0 or Summary
Report: Stock No. 017-001-00473-1) through the Superintendent of Documents,
Government Printing Office, Washington, DC 20402-9325 (telephone
202-512-1800).

ELIGIBILITY REQUIREMENTS

The collaborative CSMD mechanism requires more than one applicant
organization, although multiple campuses of a single institution are also
eligible (e.g., among the multiple campuses of a State University system).
Applications may be submitted by domestic and foreign, public or private, non-
profit or for-profit organization, including units of State and local
governments and eligible agencies of the Federal government.  The research
protocol may include one or more international components.  Typical applicants
are universities, colleges, hospitals, and laboratories.  Racial/ethnic
minority individuals, women, and persons with disabilities are encouraged to
apply as Principal Investigators.

MECHANISM OF SUPPORT

The collaborative CSMD mechanism is limited to research project (R01)
applications; no other mechanisms may be used. Applications for collaborative
CSMD may not duplicate concurrent applications or awards.

RESEARCH OBJECTIVES

Collaborative CSMD applications must have a focus on a particular scientific
issue or problem. The following are examples of broad research areas within
the NIMH research mission that might serve as a focus for collaborative CSMD. 
This list is not exhaustive, nor are the examples meant to be mutually
exclusive.

o  Large scale treatment (psychopharmacologic and/or psychosocial),
prevention, or rehabilitation trials focused on mental disorders, using common
protocols across multiple sites.

o  Studies comparing mental health service delivery and/or financing schemes
in different regions.

o  Genetic studies requiring large numbers of subjects to detect linkage of
complex disorders such as schizophrenia, mood disorders, OCD, etc.

o  Basic-Clinical collaborations involving multiple sites, some with access to
well characterized clinical samples and others with state of the art
laboratory (e.g. neuroscience, molecular genetic, etc) and/or analytic
facilities.

o  Studies of low prevalence clinical populations (e.g., childhood
schizophrenia, late-onset bipolar illness, etc.) or special populations (e.g.
minority subjects) requiring several sites to assemble a sufficiently large
sample size.

Appropriate uses of this mechanism may include, but are not limited to, the
following:

1.  To obtain a sample of research subjects that would be difficult or
impossible to recruit at a single site in a reasonable period of time.  For
example, several sites might band together to submit collaborative CSMD
application to conduct studies (e.g., genetics analyses) in which very large
sample sizes are needed for adequate statistical power, or for gender/ethnic
subgroup analyses.

2.  To broaden the base of support for a project and enhance the credibility
or generalizability of the research findings by including parallel collections
of data by investigators with differing theoretical orientations, in order to
resolve a controversial issue.  For example, there could be considerable
disagreement and uncertainty with respect to the treatment of a given
disorder, such as whether medications, psychosocial therapies, or their
combination are most effective.  Collaborative CSMD might come from a group of
investigators identified with these different positions, and with personnel at
each site properly trained to provide the treatments, results might be more
persuasive.

3.  To facilitate comparisons across multi-disciplinary laboratories, or
across a variety of mental health service systems in different geographic
areas.  An example may be the need for investigating differences in clinical
outcome, or for varied services financing schemes, which can be adequately
compared only by collecting and comparing data across multiple locations.

4.  To use the varied expertise at different institutions to investigate a
common topic.  In such cases, the tasks of a research project may be divided
among sites according to expertise available there.  This use of the
collaborative CSMD is not unlike a program project (P01), but represents
collaborations across institutions, rather than within a single institution. 
For example, some sites could recruit subjects using common
inclusion/exclusion criteria, and other sites may have specific analytic
roles.  Expertise needed on particular topics might be obtained from one site,
while different expertise could come from another site.  A site with special
strengths in clinical assessment might oversee diagnoses, another may generate
neurobiological or genetic data, while yet another might serve as the central
site for data management, analyses, and/or distribution.

Subsequent to receiving a collaborative CSMD, each principal investigator may
apply for competing supplemental funds to support promising new research
directions as they evolve. Other benefits include the establishment of
collaborations on an equal footing at separate sites (which may include
foreign locations).  Each participating investigator may benefit because the
collaborative CSMD establishes a larger framework of reference for the
proposed work and fosters formal collaborations tailored to achieving
investigator-initiated research objectives.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and
their subpopulations must be included in all NIH supported biomedical and
behavioral research projects involving human subjects, unless a clear and
compelling rationale and justification is provided 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 research involving human subjects should read the
"NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical
Research," which have been published in the Federal Register of March 28, 1994
(FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Volume 23,
Number 11, March 18, 1994.

Investigators also may obtain copies of the policy from the program staff
listed under INQUIRIES.  Program staff may also provide additional relevant
information concerning the policy.

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent approximately
two months before the anticipated application receipt date.  The letter should
include a descriptive title of the proposed research, the names, addresses,
and telephone numbers of the Principal Investigators, the identities of other
key personnel and participating institutions, and the number and title of this
program announcement.  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 avoid conflict of interest in the review.  The letter of
intent is to be sent to the program staff listed under INQUIRIES.

APPLICATION PROCEDURES

Applications are to be submitted on the grant application form PHS 398 (rev.
5/95) and will be accepted at the standard application deadlines as indicated
in the application kit.  The receipt dates for applications for AIDS-related
research are found in the PHS 398 instructions.  Application kits are
available at most institutional offices of sponsored research and may be
obtained from the Division of Extramural Outreach and Information Resources,
National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD
20892-7910, telephone (301) 710-0267; fax (301) 480-0525; Email
[email protected].

Separate applications must be prepared by each participating institution.  It
is crucial that all applications comprising the collaborative CSMD cite this
program announcement title and number (PAR-98-017) in section 2 on the
application face page.

The completed original applications and five legible copies from each
institution must be sent or delivered to:

CENTER FOR SCIENTIFIC REVIEW (formerly Division of Research Grants)
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710, or
BETHESDA, MD  20817 (for express/courier service)

It is conceivable that one or more collaborative CSMD applications may be
continuations of currently funded R10s, IRPGs, or separate (i.e., previously
non-collaborative) grants, with others being new (Type 1) R01s, all seeking
support to come under the umbrella of the collaborative CSMD program.  In such
cases, the competing renewal (Type 2) applications will keep the same grant
number as usual. However, it is essential that the following information be
incorporated identically into all collaborative CSMD applications:

1.  The application from each site must contain an OVERVIEW that is no longer
than two pages.  It should list the individual participating sites and provide
justification for applying as collaborative CSMD.  This section should also
make clear the roles of each participating site.

2.  RESEARCH PLAN - Section 2 A - D,  should describe those aspects of the
project that are common to all sites of the collaboration.  Investigators
should use this section to describe the research procedures or protocol, the
study population from which samples are drawn, resources, data analyses, and
any other characteristics that support each site?s importance to the overall
project.  Where there are even minor variations in the research plan, these
should be highlighted in a subsection of Section 2 D with the heading
"ELEMENTS UNIQUE TO THIS SITE."

3.  Applications must describe a feasible mechanism for scientific integration
of research procedures, overall managerial and administrative
responsibilities, and cross-site comparability of training to assure
reliability and quality control.  The PIs may or may not wish to designate a
Steering Committee or other decision making body, or identify one individual
as the contact person for the group as a whole, for purposes of NIMH
correspondence. Plans for ensuring access to data by all sites, analytic
resources, publication and authorship rights, the possibility of public use
research materials and data, or other means of distributing research materials
to the wider scientific community, and a means of arbitrating disagreements on
publication and other issues should be found in this section of the
application.

4.  Any site that contracts out some portions of this work should list this
fact under "ELEMENTS UNIQUE TO THIS SITE," and provide a full description of
the nature, purpose and oversight of this contractual arrangement.  As per
instruction in the PHS 398 kit, the application may also contain an APPENDIX,
including up to 10 publications or other printed material; surveys,
questionnaires, data collection sets and clinical protocols; and original
glossy photographs provided that photocopies are also included within the 25
page limit of the research plan.

In accordance with NIH policy, incomplete applications will be returned by the
Grants Referral Office.

Revised collaborative CSMD applications must include an Introduction and
highlight the changes made in the Research Plan in response to the previous
critique and describe in item (I) how the delay in initiating the
collaboration will be managed.  This is particularly important if some
projects in the collaborative CSMD group were awarded and research on those
projects has already begun.

REVIEW CONSIDERATIONS

Applications that are complete will be evaluated for scientific and technical
merit by an appropriate peer review group convened in accordance with the
standard NIH peer review procedures. As part of the initial merit review, all
applications will receive a written critique and undergo a process in which
only those applications deemed to have the highest scientific merit, generally
the top half of applications under review, will be discussed, assigned a
priority score, and receive a second level review by the National Advisory
Mental Health Council, when applicable.  Individual applications may receive
differing priority scores and/or recommendations.  The review committee may
not, however, recommend approval of fewer than two sites.

Review Criteria

Each application within the Collaborative CSMD will be evaluated on the merit
of the overall project plan, the merit of each site's individual
contributions, and the relationship between these two aspects.  Applications
will be evaluated according to the following general review criteria:

(1) Significance:  Do these studies address an important problem?  If the aims
of the applications are achieved, how will scientific knowledge be advanced? 
What will be the effect of these studies on the concepts or methods that drive
this field?

(2) Approach:  Are the conceptual framework, design, methods, and analyses
adequately developed, well-integrated, and appropriate to the aims of the
proposed projects?  Do the applicants acknowledge potential problem areas and
consider alternative tactics?

(3) Innovation:  Do the projects employ novel concepts, approaches or methods?
Are the aims original and innovative?  Do the projects challenge existing
paradigms or develop new methodologies or technologies?

(4) Investigators:  Are the investigators appropriately trained and well
suited to carry out this work?  Is the work proposed appropriate to the
experience level of the principal investigators and other researchers (if
any)?

(5) Environment:  Do the scientific environment(s) in which the work will be
done contribute to the probability of success?  Do the proposed experiments
take advantage of unique features of the scientific environment(s) or employ
useful collaborative arrangements?  Is there evidence of institutional
support?

In addition, the following specific issues will be evaluated:

o  The scientific rationale for the overall collaborative CSMD, including
scientific, technical, or medical significance, originality, and
innovativeness of proposed interactive program.

o  The plan for management (e.g., steering committee or other governing body)
of the project across sites, including coordination, decision making, quality
control, and resolution of disagreements.

o  Availability of the resources at each site necessary to carry out the
research.

o  Appropriateness of the proposed budget and duration at each site.

o  Procedures to ensure access to data, sharing of data and resources (both
within and outside the collaborative CSMD group), publication rights, and
means of arbitrating and resolving publication disagreements among the
participating investigators.

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

o  Provisions for the protection of human and animal subjects, the safety of
the research environment, and conformance with the NIH Guidelines for the
Inclusion of Women and Minorities as Subjects in Clinical Research.

AWARD CRITERIA

Collaborative CSMD applications will compete with all other research project
grant applications for available funds. Award decisions are based on the
following criteria: 1) scientific merit as determined by the review committee;
2) availability of funds; 3) programmatic balance; and 4) Institute
priorities.

INQUIRIES

Inquiries are encouraged.  The opportunity to clarify any issues or questions
from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Barry D. Lebowitz, Ph.D.
Division of Services and Intervention Research
National Institute of Mental Health
Parklawn Building, Room 10-77
Rockville, MD  20857
Telephone:  (301) 443-1185
FAX:  (301) 443-4045
Email:  [email protected]

Direct inquiries regarding fiscal matters to:

Diana S. Trunnell
Grants Management Branch
National Institute of Mental Health
Parklawn Building, Room 7C-08
Rockville, MD  20857
Telephone:  (301) 443-2805
FAX:  (301) 443-6885
Email:  [email protected]

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No.
93.242.  Awards are made under authorization of the Public Health Service Act,
Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC
241 and 285) and administered under PHS grants policies and Federal
Regulations 42 CFR 52, and 45 CFR Part 74.  This program is not subject to the
intergovernmental review requirements of Executive Order 12372 or Health
Systems Agency review. Awards will be administered under PHS grants policy as
stated in the Public Health Service Grants Policy Statement (April 1, 1994).

PHS strongly encourages all grant and contract recipients to provide a smoke-
free workplace and promote the nonuse 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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