RFA-MH-02-001: AUTISM RESEARCH CENTERS OF EXCELLENCE: THE STAART PROGRAM

AUTISM RESEARCH CENTERS OF EXCELLENCE: THE STAART PROGRAM

Release Date: June 18, 2001

RFA: RFA-MH-02-001

National Institute of Mental Health (NIMH)
(http://www.nimh.nih.gov/)
National Institute of Child Health and Human Development (NICHD)
(http://www.nichd.nih.gov/)
National Institute of Neurological Disorders and Stroke (NINDS)
(http://www.ninds.nih.gov/)
National Institute on Deafness and Other Communication Disorders (NIDCD)
(http://www.nidcd.nih.gov/)
National Institute of Environmental Health Sciences (NIEHS)
(http://www.niehs.nih.gov/)

Letter of Intent Receipt Date: August 29, 2001
Application Receipt Date: November 29, 2001

PURPOSE

The National Institutes of Health Autism Coordinating Committee (NIH/ACC) is
implementing the aspects of the Children's Health Act of 2000 that relate to
support of autism research by NIH. The NIH/ACC is composed of the NIH
institutes currently funding autism research: NIMH, NICHD, NINDS, NIDCD, and
NIEHS. An important aspect of these activities is the establishment of
Centers of Excellence in Autism Research, and in this RFA the participating
institutes invite research grant applications for such Centers. These
Centers will constitute a cohesive program, operating under an NIH
cooperative agreement, which will be called the STAART Centers Program
(Studies to Advance Autism Research and Treatment).

The primary goal of this initiative is to establish several research centers,
each of which will bring together expertise, infrastructure and resources
focused on major questions about autism. The research issues to be addressed
will include causes, diagnosis, early detection, prevention, and treatment,
with approaches such as developmental neurobiology, genetics, and
psychopharmacology being represented. Centers should use innovative research
designs and state-of-the-art technologies. Centers should draw upon
established basic and clinical scientists to form unique collaborations
optimally suited to address the research questions posed. Achieving high
levels of expertise and resources may require multi-institutional consortia
to be formed. Centers are expected to provide an environment and core
resources which will enhance ongoing research by bringing together
biomedical, behavioral, and clinical science investigators to study autism.
The centers will provide investigators with well-characterized patients and
control subjects, family information, and other scientific resources that
will facilitate research projects. Each center should develop in accordance
with available expertise, interests, and resources, but should also be
responsive to national needs related to autism. While types of activities
that should be included are indicated in these guidelines, specific
approaches to accomplish them are left to applicants.

In addition to the self-contained activities of individual centers, the
STAART Centers Program will conduct collaborative studies among centers which
will be overseen by a Steering Committee for the Program involving
representation from each center and from NIH. The STAART Centers Program
will be be funded through an NIH Cooperative Agreement mechanism, the goal of
which is to maximize the collaborative utilization of the unique resources in
infrastructure, expertise, and clinical recruitment that will be created.

Investigators interested in applying for support of autism research using
mechanisms other than this RFA should see NIH PA-01-051
(http://grants.nih.gov/grants/guide/pa-files/PA-01-051.html) for a
description of NIH's broad support of autism spectrum research through a
number of other grant mechanisms. Investigators potentially interested in
applying for support to develop into competitive research teams for Centers
of Excellence support should see NIH RFA MH-01-013
(http://grants.nih.gov/grants/guide/rfa-files/RFA-MH-01-013.html).

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 Request for
Applications (RFA), Centers of Excellence in Autism Research: The STAART
Program, is related to one or more of the focus areas. Potential applicants
may obtain a copy of "Healthy People 2010" at
http://www.health.gov/healthypeople.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic for-profit and non-profit
organizations; public and private institutions, such as universities,
colleges, hospitals, laboratories, units of State and local governments; and
eligible agencies of the Federal government. Applications prepared for this
competition may propose multi-institutional consortium arrangements. While
the applicant institution must be domestic, foreign institutions may be
involved in a consortium. For example, a project within the center may be
located at a foreign institution and supported through a subcontract.
Racial/ethnic minority individuals, women, and persons with disabilities are
encouraged to apply as Principal Investigators.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) specialized
cooperative research center (U54) award mechanism, 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 it is not to assume direction, prime responsibility, or a
dominant role in the activity. Details of the responsibilities,
relationships, and governance of the studies to be funded under
cooperative agreements are discussed below under Terms and Conditions of
Award. Potential applicants may obtain the NICHD U54 Specialized Cooperative
Research Center Grant Guidelines at http://www.nichd.nih.gov/funding/mechanism/u54_guide.cfm.
With certain exceptions, specified below, the information provided there is
applicable to this RFA, including the preparation of applications.

Applicants should request five years of support. It is anticipated that
competitive renewal applications for a second 5-year period will be allowed.
Individual projects that are developed as outgrowths of a STAART Center grant
and are no longer an integral part of the center should seek independent
funding.

FUNDS AVAILABLE

Each center application may request a maximum of $1.2 million per year direct
costs. Facilities and Administration (F&A) costs on subcontracts will be
listed as direct costs on budget pages as is the usual NIH practice, but they
will not count against the cap of $1.2 million. The estimated total funds
(direct and F&A costs) available for support for all awards made under this
and subsequent RFAs for the STAART Centers Program are anticipated to be $12
million per year. This total amount will be used to fund the complement of
at least 5 centers, a data coordination center, and collaborative projects
among the centers. There will be at least two rounds of competition for
STAART Centers, with deadlines of November 29, 2001 and August 29, 2002. A
new RFA will be issued to solicit applications for second receipt date.
Whether there are subsequent rounds of competition will depend on the number
of centers funded in these first two rounds and available funding. The
ultimate number of centers funded will be at least 5 and will depend upon the
merit of the applications received and the funds available. The award of
grants pursuant to this RFA is contingent upon the availability of funds for
this purpose. Only applications of sufficiently high merit will be funded.

The majority of the $12 million pool of funds will be distributed to
successful center applicants to support the activities specific to each
center. A separate portion of this pool of funds will be distributed to
centers to fund specific cooperative projects among the centers, and another
portion of the pool will be used to fund a data coordination center for which
there will be a separate RFA in the future. The exact nature of the
cooperative studies will be determined by the Steering Committee of the
STAART Centers Program. Investigator-initiated requests for competitive
supplements will not be allowed in the STAART Program.

RESEARCH OBJECTIVES

Background

o Organization of initiatives relevant to the STAART Program. Public Law
106-310, The Children's Health Act of 2000, authorizes the Director of NIH,
acting through the Director of the National Institute of Mental Health
(NIMH), to expand autism research activities in general and to support the
planning and establishing of no fewer than five Centers of Excellence in
Autism Research. This RFA solicits applications for such center support
under the STAART Centers Program.

o Appropriateness of proposed research for center support rather than R01
support. The NIH has long supported a variety of autism research projects
through R01, P01, small grant, and career development mechanisms. Those
types of support will continue, and many new and continuing projects will be
more appropriate for those mechanisms. What distinguishes a research program
that is appropriate for STAART support from a research program that is better
supported through a series of R01 grants? The STAART Program, funded through
the U54 mechanism, supports major multidisciplinary research programs,
consisting of interdependent and interrelated subprojects, cores, and
infrastructure. "Multidisciplinary" is defined as having subprojects
representing different disciplines, approaches, and expertise exploring a
common or unifying theme. This feature alone does not constitute a rationale
for the use of a center mechanism, since many individual investigator-
initiated research grants (R01s) are multidisciplinary in nature. Meaningful
and committed interactions among the disciplines must be evident.
"Interdependent" means that materials, results, data, patient populations, or
methodologies are shared among the subprojects. Results of one subproject may
well affect the understanding and interpretation of data from another project
and thereby influence the nature of the research being performed in one or
more of the other subprojects. The feasibility of the research proposed on
any subproject might be significantly diminished if that subproject were
submitted as a traditional individual research grant (R01) application.
However, diminished feasibility is not, in itself, justification for
inclusion of an independent subproject in a Centers application. In addition,
each subproject must have goals and objectives that focus on the common
unifying theme to be considered interrelated.

In all cases, the necessity for concurrent funding of the subprojects and
cores must be specified and fully justified (e.g., longitudinal study on a
unique and difficult to acquire subject population; the data must be
collected from the same subjects in a time-dependent fashion; the data from
one subproject directly impact the conduct of the research on one or more of
the other subprojects). Core support must be justified as providing essential
resources to the center's projects.

o Description of STAART support mechanisms. The NIH Guide to Grants and
Contracts describes the plan for implementation of Centers of Excellence in
Autism Research
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-039.html).
Three related competitive application processes are planned.
There will be two application deadlines for comprehensive centers (November 29,
2001 and August 29, 2002). Additionally, there is a July 12, 2001
deadline for developmental grants that are intended to support investigative
teams to plan and develop a comprehensive center application. These
mechanisms are described in more detail below.

Previously, the NIH/ACC institutes released RFA-MH-01-013
(http://grants.nih.gov/grants/guide/rfa-files/RFA-MH-01-013.html) containing
a set-aside for research support to develop autism center applications for a
FY2002 deadline. The RFA for developmental grants will support investigative
teams to maximize the probability that they will become highly qualified
applicants. Each award under that initial RFA will be for 1 year and a
maximum of $100,000 for direct costs ($125,000 if multiple institutions are
involved). The earliest possible start date for the developmental awards is
September 30, 2001. It is anticipated that the developmental grants RFA will
be a one-time solicitation. These developmental grants are intended to
assist investigators who will apply for the September 01, 2002 deadline to
become part of the STAART Centers Program, with anticipated funding of
successful applications in FY 2003.

The present RFA (RFA-MH-01-014) is intended for applicants who wish to apply
for center support on an earlier timeline and without participating in the
developmental grant process. Applicants may apply for either developmental
support by the July 12, 2001 deadline under RFA-MH-01-013, or by the November
29, 2001 deadline as a comprehensive center under the present RFA, but they
may not compete for both. Applicants who submit a developmental grant
application for the July 12, 2001 deadline or a comprehensive center
application for the November 29, 2001 deadline and are not successful may
submit a revised application for STAART center support for the August 29,
2002 deadline, as may new applicants who have not previously responded to
either of these solicitations.

Thus, applicants can compete for STAART support in one of three ways: 1)
applying for a developmental grant in July 2001, with the intention of then
applying for a comprehensive center grant in August 2002; 2) applying for a
comprehensive center grant in November 2001, with the option to re-apply in
August 2002 if unsuccessful; or 3) applying for a comprehensive center grant
in August 2002.

Goals of the STAART Centers Program

Even given the promising growth of the clinical and basic research fields
relevant to autism, and the interaction among investigators in the field that
has been cultivated by sustained NIH support of the Network on the
Neurobiology and Genetics of Autism, 10 Collaborative Programs of Excellence
in Autism (CPEA) program, the STAART Centers Program will represent a
substantial increase in the scope of the scientific enterprise related to
this disorder, particularly as it provides a specific emphasis on and direct
funding for treatment research.

The primary goal of the present initiative is to support cohesive teams of
accomplished investigators focused on basic and clinical issues related to
autism. STAART support will provide investigators within each center the
opportunity to pursue common goals and objectives, work as an integrated,
interactive research team, and develop the resources, equipment, or
administrative support needed to operate an interdisciplinary center. This
type of multidisciplinary, multi-faceted research is of paramount importance
in elucidating the etiology, pathophysiology, and evidence-based treatment of
autism. It is expected that the STAART Centers will produce innovative,
potentially high-impact approaches to fundamental research problems. It is
also anticipated that STAART Centers will attract outstanding investigators
who have not have been part of the autism field.

Examples of scientific areas that could be appropriate foci for STAART
Centers activities are:

o development of new or improved treatments, in behavioral/psychosocial,
pharmacological, and other biological modalities

testing safety & efficacy of treatments now used
translation of basic research into novel therapies
pharmacogenetics
pharmacokinetics
development of new outcome measures

o development of methods for early diagnosis and screening, including
biological and behavioral indices for early detection

o investigation of neural bases and pathways for abnormal behaviors

o investigation of potential environmental etiologies and risk factors
including

prenatal
infectious
toxic
immunizations

o description and characterization of co-morbidities, and how they relate to
etiology, pathology, and prevention: for example, brain - gut connection,
gastrointestinal abnormalities, epilepsy, obsessive-compulsive disorder

o neuroimaging investigations using functional magnetic resonance imaging,
brain mapping, other new technologies to determine neuroanatomic and
localized functional abnormalities and how they change over time

o genetic studies including gene-environment interactions, candidate genes,
and genotype-phenotype correlations

o studies of language and disorders of communication

o interventional, descriptive, and neuroimaging studies which utilize a
related comparison group such as fragile X, obsessive-compulsive disorder,
mental retardation, tuberous sclerosis, Williams syndrome

o development of novel animal models

These are examples and by no means inclusive. There are many other potential
areas of study that applicants might choose to emphasize.

The Children's Health Act. As noted above, the Children's Health Act
contains specific provisions regarding the centers it mandates. All of these
will be considered in the review of the Centers applications. The relevant
text of the Act is as follows:

“(1) IN GENERAL.— The Director [of NIH] shall under subsection (a)(1)
make awards of grants and contracts to public or nonprofit private entities
to pay all or part of the cost of planning, establishing, improving, and
providing basic operating support for centers of excellence regarding
research on autism.

“(2) RESEARCH.— Each center under paragraph (1) shall conduct basic and
clinical research into autism. Such research should include investigations
into the cause, diagnosis, early detection, prevention, control, and
treatment of autism. The centers, as a group, shall conduct research
including the fields of developmental neurobiology, genetics, and
psychopharmacology.

“(3) SERVICES FOR PATIENTS.-

“(A) IN GENERAL.— A center under paragraph (1) may expend amounts provided
under such paragraph to carry out a program to make individuals aware of
opportunities to participate as subjects in research conducted by the
centers.

“(B) REFERRALS AND COSTS.— A program under subparagraph (A) may, in
accordance with such criteria as the Director may establish, provide to the
subjects described in such subparagraph, referrals for health and other
services, and such patient care costs as are required for research.

“(C) AVAILABILITY AND ACCESS.— The extent to which a center can demonstrate
availability and access to clinical services shall be considered by the
Director in decisions about awarding grants to applicants which meet the
scientific criteria for funding under this section.

“(4) COORDINATION OF CENTERS; REPORTS.- The Director shall, as appropriate,
provide for the coordination of information among centers under
paragraph (1) and ensure regular communication between such centers, and may
require the periodic preparation of reports on the activities of the centers
and the submission of the reports to the Director.

“(5) ORGANIZATION OF CENTERS.- Each center under paragraph (1) shall use the
facilities of a single institution, or be formed from a consortium of
cooperating institutions, meeting such requirements as may be prescribed by
the Director.

“(6) NUMBER OF CENTERS; DURATION OF SUPPORT.-

“(A) IN GENERAL.- The Director shall provide for the establishment of not
less than 5 centers under paragraph (1).

“(B) DURATION.- Support for a center established under paragraph (1) may be
provided under this section for a period not to exceed 5 years. Such period
may be extended for 1 or more additional periods not exceeding 5 years if the
operations of such center have been reviewed by an appropriate technical and
scientific peer review group established by the Director and if such group
has recommended to the Director that such period should be extended.”

The specific provisions of this RFA are intended to implement these
provisions of the Act. For example, the requirement of the Act that each
center shall conduct basic and clinical research is interpreted in this RFA
to mean that it is mandatory for applications to include both clinical and
basic studies to be considered responsive to this RFA. For this purpose,
clinical research is considered to be research involving individuals with
autism that deals with biomedical and/or behavioral aspects of the disorder.
Basic research is considered to be studies dealing with normative processes
in people, animals, or in vitro preparations. As another example, the Act
indicates a spectrum of targeted research topics that are appropriate for
centers. For the review of STAART applications, a principal criterion for
evaluation will be the extent to which the center projects directly, and as
comprehensively as possible, address these topics. However, although a
comprehensive representation of these topics is desirable, it is expected
that a given proposed center may have only a limited capacity to address
certain topics. Thus, it is expected that each funded center will address a
majority of these topics with substantive, high-quality research proposals
and will develop additional capacity for more comprehensive efforts over
time.

o Collaborative studies. In addition to these issues that are focused on
individual centers, a major goal of the STAART Centers Program is to
establish a major research network that, as a whole, will be capable of
implementing large treatment, diagnostic, genetic, neuroscientific and other
studies, which are not currently feasible. To accomplish this, the U54
mechanism is being used to support the centers, and there will be active
involvement of NIH staff in coordinating collaborative studies that will be
defined and implemented after the initial centers are funded. Also, there
will be funds from the overall funding pool that will be designated for
collaborative studies so that appropriate budget supplements and/or increases
can be distributed to the participating centers. However, it is expected
that each center will contribute reasonable subject recruitment and follow-up
functions to these collaborative studies without budget supplementation.

It is expected that the STAART-wide collaborative studies will emerge from
common scientific interests among the funded centers. Therefore, it is
appropriate for applicants to describe studies they would be particularly
interested in that might utilize the resources of the STAART Centers Program.
Such a study might, for example, be a pharmacological or psychosocial
treatment study or an investigation of early signs of autism that would not
have sufficient power without the resources of the program.

ORGANIZATION OF STAART CENTERS

Each STAART Center will have a Center Director (the Center Principal
Investigator) who will make scientific and administrative decisions relating
to the center, will oversee identification and selection of key personnel,
and will be responsible for allocation and monitoring of STAART funds. These
responsibilities and decisions will be undertaken with the advice of the
executive committee and the External Consultants Committee described below.
There will also be a Co-Director. The Director and Co-Director should have a
demonstrated capability to organize, administer and direct the center. It is
expected that the Director and Co-Director will have a substantial investment
in the center and be its scientific leaders. Thus, each should have a
minimum total (including core and project commitments) time commitment of 20%
to the STAART Center.

Each center will have a team of appropriate investigators, a set of research
projects, a collection of support cores, and appropriate infrastructure and
institutional support that will allow the proposed center to accomplish the
goals of the STAART Centers Program.

STAART support is not intended to be a substitute for individual grant
support. It is, therefore, expected that project and core leaders will have
independent, peer-reviewed research support. Neither should the STAART
Center be the primary source of research funding for the investigators
associated with the Center. It is desirable for STAART-supported research to
complement other funded research related to autism taking place at the
applicant institution, including activities supported by R01, P01, P30, P50
and other mechanisms. Investigators with the qualifications to be members of
the research team, and to contribute to such a unique enterprise, may be
located in different geographic locations. Therefore, collaborations among
different institutions are encouraged, if scientifically appropriate. The
proposed team will be responsible for the definition of the research goals
and objectives of the research enterprise, as well as ongoing activities.

Each STAART Center applicant must demonstrate the ability to perform the
necessary administrative, clinical, and information utilization functions.
A possible structure is outlined below, in which these functions are
organized into new cores that would be established with STAART funding.
However, there are no mandatory cores, and applicants may propose other ways
of accomplishing these functions, such as integrating them with already
existing structures. Also, other cores may be proposed.

There should be institutional resources set in place to provide the
components that make the site(s) competitive for Center of Excellence
support. There should be substantive departmental and institutional support
for and commitment to the proposed center.

Applications should provide a description of the clinical populations,
patient, family, and control subject information, tissue resources, genetics
resources, and other resources that will be involved as part of the team's
clinical research component. It is anticipated that resources and projects
that are in place due to funding from sources other than the STAART Program
will synergistically interact with STAART infrastructure, cores, and
projects. The application should explain how STAART support would facilitate
the development and significance of related projects that may not be an
integral component of the STAART itself. In such cases, it will also be
necessary to address, in detail, questions of possible overlap of support
from other grants or funding sources.

STAART Centers must commit to cooperate fully and to share data concerning
patients, control subjects and specimen resources within the STAART Centers
Program, and with the broad scientific community, as specified by NIH.

Cores

A core is a shared central laboratory or clinical research facility, service,
or resource. Each core is directed by a faculty investigator (the Core
Director) with substantial expertise related to the core. Two important and
related considerations are (1) the degree to which currently funded
investigators within or outside the center will use and will benefit from
core resources and (2) the degree to which the resources will promote new
and/or expanded autism research efforts locally, regionally or nationally.
Applicants should document and describe briefly the projects, both existing
and planned, whether funded by the center or not, that will depend upon
resources provided by the cores (clinical cores, in particular).

o Administrative core. The successful operation of each STAART Center will
require the integration of the activities of several projects and cores, as
well effective organization of the efforts of scientific and professional
personnel from a variety of disciplines and subspecialties. This requires
the presence of an administrative structure to organize the flow of
information, distribution of effort, allocation of resources, and to
implement other necessary administrative functions. This will require an
administrative core or its equivalent.

The administrative requirements of each STAART Center will necessitate the
assistance of an administrator with business management expertise. It is
important that such an individual be identified and directly involved with
the fiscal and administrative aspects of the STAART application and grant.
It is expected that the STAART Center administrative structure will
facilitate the following:

1) coordination and integration of STAART components and activities

2) planning and review of utilization of funds

3) provide support and advice for the STAART Director in his/her oversight of
the activities of the center

4) interact with the scientific and lay communities to develop relevant goals
for the STAART Center within the immediate environment of the Center

5) interact with other STAART Centers and the center's NIH Science Officer to
develop trans-STAART research projects. The Science Officer is the NIH
representative who implements the NIH aspects of the Cooperative Agreement in
each center.

An executive committee (composed of core directors, project leaders, and the
administrator) will be established in each center to assist the Center
Director and Co-Director in making scientific and administrative decisions.
The executive committee should be encouraged to seek outside advice and
consultation, both from within the institution and from other institutions,
in its monitoring and development of the scientific content and direction of
the program.

An External Consultants Committee to each STAART Center, consisting of
scientists from outside of the institution or consortium, will also be
established. Unless already appointed, External Consultants Committee
members should not be recruited until the NIH review process is complete.
This committee will be used to evaluate the programs of the center, research
progress, the effectiveness of communications within the center, and any
other activities for which outside expertise is required or desirable. The
committee should meet annually and prepare a report including recommendations
to assist the center. The NIH Science Officer for that center and the
Program Officer for the STAART Program should be invited to attend each
meeting as observers. A copy of the advisory committee report should be sent
to the appropriate NIH Science Officer and to the Program Officer.

o Clinical core. The STAART Center will provide well-characterized
patients, patient and family information, and biological samples from persons
with autism and appropriate control subjects for center research projects and
for collaborative research projects across the STAART Centers Program. The
clinical core serves the functions of patient and control subject
recruitment, evaluation, and diagnosis; establishing and maintaining a
subject registry; longitudinal follow up of patient and control subjects;
acquisition of clinical and laboratory data; and data coordination and
biostatistical analysis (if not included as a function of the administrative
core or a separate data core). A research database that maintains
confidentiality of all patient and control subject records should be
established at each STAART Center.

A clinical core may perform a limited amount of developmental work, but
should not directly be used as a mechanism to fund research per se. The
developmental work allowable in a clinical core must be directly related to
the function of the core. It may be directed toward improving and expanding
the core functions, e.g., improving existing diagnostic strategies, or
developing additional methodologies, techniques or services. Proposed
developmental work should be described as completely as possible in the
application. Planning for patient and appropriate control subject
recruitment should include sensitivity to ethical concerns, research design
and biostatistical analysis. While conducting clinical treatment trials is
one function of a clinical core, it should not be the major effort of the
core. The application should include a description of the types (with
specific examples) of research projects and clinical trials that will use the
core and what benefits will obtain to other research activities from the
existence of the clinical core. The proposed procedures for allocating
access to patient and control subjects across the STAART projects within the
center should be described.

It is important to note that the only patient care costs that can
appropriately be supported by STAART funds are those that are essential for
research activities. Thus, it is important for each application, whether or
not a clinical core is proposed, to describe the local resources available,
the institutional commitment to maintaining clinical resources, and the way
in which the already existing and the planned resources would be used to
provide recruitment, referral, and information resources for patients and
their families. The aspects of the Act relevant to these issues should be
directly and comprehensively addressed in the application.

Applicants must demonstrate a data management capability either by creating a
feasible data core or by having a clearly defined data management section in
the administrative or clinical core. In any case, data management should
also include biostatistical consulting to the scientific members of the
center.

o Scope of appropriate subject populations. STAART studies can
appropriately focus on any of the autism spectrum disorders and on either
children or adults with these disorders or at risk for these disorders, and
comparison groups appropriate for the scientific questions proposed, for
example, people with fragile X, obsessive compulsive disorder, Williams
syndrome, mental retardation, schizophrenia, or normally developing children
or adults. The primary criteria for determining inclusion of a particular
subject pool are scientific. That is, the applicant must justify the
inclusion of particular subject groups as being of scientific interest and as
being justified given the hypothesis being tested, the experimental design,
and feasibility issues.

Efforts to recruit diverse population subgroups including children,
minorities and women must be outlined.

o Neuropathology and genetics activities. It is anticipated that the STAART
Centers Program will offer important opportunities for enhanced collaborative
collection of materials and data in the areas of genetics and neuropathology.
Although, not every center may wish to propose substantive cores or projects
in these areas, each center applicant should indicate, through core and
project proposals, or through a statement of intent included in the
application, their intention to participate in collaborative STAART
activities in these areas.

Possible Additional Cores

The STAART Centers Program will support additional cores that provide
opportunities for scientific accomplishments beyond those attainable solely
through support of the suggested cores. It is important to note that support
should not be requested for cores that only replace or centralize resources
supported on individual project grants. In a Center grant application, it is
not sufficient for the principal investigator merely to identify such
centralized resources. Rather, it must be demonstrated exactly how each core
would augment or enhance the present capabilities of the investigators and
make possible new activities. There should be a thorough discussion of the
project(s) that will use resources of additional cores.

Genetics Data Sharing in the STAART Program

NIH has a strong interest in the sharing of data and other resources produced
through its funding, and has long-standing policies in this area (for the
most recent statement, see the NIH Grants Policy Statement, page II-62,
“Unique Research Resources,” published in October 1998, related to the
distribution of unique research resources produced with DHHS funding
(http://grants.nih.gov/grants/policy/nihgps/). More specific policies have
been promulgated from time to time to address the needs of particular areas
of research. For example, NIH has worked with journals and databases to
encourage the rapid placement of unpublished DNA sequence data and
crystallographic coordinates into public databases. The National Human
Genome Research Institute has a policy that all genomic data, whether
published or not, should be shared as rapidly as possible and placed in the
public domain
(http://www.nhgri.nih.gov/Grant_info/Funding/Statements/RFA/new_data_release.html).
For grantees engaged in large-scale sequencing, the policy specifies
data release within 24 hours of generation
(http://www.nhgri.nih.gov/Grant_info/Funding/Statements/RFA/data_release.html).

After extensive discussion with mental health and human genetics researchers
and advocacy members, a Genetics Workgroup of the National Advisory Mental
Health Council (NAMHC) recommended that the National Institute of Mental
Health (NIMH) draft a policy that provides for the sharing of genetic
materials after a 12- to 18-month proprietary period. The workgroup report
is available at http://www.nimh.nih.gov/research/genetics.htm. It was also
recommended that this policy include all elements of the guidelines developed
by NIH and the Department of Energy (DOE) to address the special needs of
genome research
(http://www.nhgri.nih.gov/Grant_info/Funding/Statements/data_release.html).
Sharing within the scientific community of genetic material and data
collected in large-scale human genetic studies has been a guiding principle
of NIMH’s Human Genetics Initiative http://zork.wustl.edu/nimh/.

Each application for STAART support must include a plan for the sharing of
genetic materials and data. This plan will be evaluated during the peer
review of the application. This sharing plan should address the issues
raised in the following paragraphs. The timeline for sharing of genetic data
will be compatible with the timeline for sharing of other types of data as
described in TERMS AND CONDITIONS under 6. Public Domain of Data (below).

Creation of high-quality lymphoblastoid cell lines from blood samples
establishes an infinitely renewable source of DNA for subsequent genetic
analyses. In addition, these biological materials will be an invaluable
resource for future studies that employ genetic maps of much higher density
(e.g., those with single nucleotide polymorphisms as a basis) and that employ
efficient technologies to study gene function and expression. Cell lines are
an essential resource to permit broad sharing of data and biomaterials for
genetic analyses in the wider scientific community. Therefore, it is expected
that permanent cell lines will be established for subjects studied in STAART
projects and that these will be shared with the scientific community. Any
proposed use of cell lines in STAART projects other than for sharing will
require a compelling scientific rationale in the application. Appropriate
arrangements should be included in the proposed sharing plan.

It is expected that the information to be shared includes clinical,
diagnostic, and pedigree structure information (excluding all personal
identifiers), in addition to cell lines and DNA. It is expected that the
data sharing plan will include the following elements: 1) the creation of
comprehensive and verified databases that contain clinical, diagnostic,
pedigree structure, and genotypic information collected and produced in the
STAART Center; 2) the establishment of high-quality cell lines, from which
DNA will be extracted and stored, for all subjects studied from whom blood
samples have been obtained; 3) mechanisms by which all databases and
biological materials (DNA samples, cell lines) are widely distributed to
qualified investigators in the scientific community; 4) a protocol and
criteria for wide dissemination of these data and materials; and 5) a
timetable for distribution. The plan will be considered part of the
scientific methodology for carrying out the research and, as such, the
adequacy of the plan will be considered in determining whether the project
shall be funded. The sharing plan as approved, after negotiation with the
applicant when necessary, will be a condition of the award.

It is NIH’s position that dissemination of data and biomaterials via
individual laboratories and Web sites is not sufficient, as it would force
interested investigators to have to search several different data collections
to make use of the results. In addition, differences in protocols across
projects for creating databases, establishing cell lines, and extracting DNA
may make it impossible for researchers to combine information for integrated
genetic analyses. It is highly preferable that data and materials generated
in such grants should be placed in common, accessible cell repositories and
databases that are widely available to investigators in the scientific
community. Such data management and cell repository facilities include the
NIMH Center for Genetic Studies (http://zork.wustl.edu/nimh/) and the Autism
Genetic Resources Exchange (AGRE; http://www.agre.org/).

General Data Sharing Policies and Data Coordination Facility for the STAART
Centers Program

It is expected that the STAART Program will become a valuable resource for
research advances in the study of autism. The data generated by this
resource will be extremely important and their impact will be optimized only
by implementing successful data sharing policies and data storage and
management infrastructure. The specifics of the policies that will
eventually be implemented will be determined among the funded centers and NIH
staff in meetings and negotiations conducted after the initial group of
centers is funded. These policies will include a variety of types of data
and materials.

It is anticipated that the STAART Program will establish and support a
centralized data management facility that will collect, store, coordinate and
distribute data from all member centers. This will facilitate the
standardization and usefulness of the information collected at the various
sites. A separate RFA for proposals to establish and operate the centralized
data facility will be issued in the future.

RESEARCH PROJECTS

Applications must include a minimum of three and a maximum of six proposed
research projects. The research projects should be proposed for five years
of funding and incorporate the latest techniques and propose studies that
will advance our understanding of the basic and clinical underpinnings of
autism in areas such as etiology, genetics, pathogenesis, epidemiology,
diagnosis, therapeutic interventions, patient management, and care giver
issues. The projects should be similar in quality and scope to moderately
sized R01 grants and subprojects of program project grants. For projects
using patients, it is essential that the expectations for numbers of subjects
be clearly stated and that the proposed source of these subjects be
identified so that the overall picture of subject recruitment and
availability can be critically evaluated for the entire center. It is
preferable that the center projects demonstrate a high level of
interrelatedness among themselves. The rationale for inclusion in the
center, rather than implementing these as individually supported projects
(e.g., via R01 support) should be provided.

In order for an application to receive funding as a STAART Center, there must
be at least 3 fundable research projects, at least one of which must be a
treatment study.

MEETINGS

In order to assure active collaboration with other STAART Centers, the
Director, Co-Director, project directors, and other key personnel should
attend STAART Centers Program annual meetings and other ad hoc meetings that
may be called to share research findings and plan for collaborative research
projects or to refine and standardize operating procedures among the Centers.
The STAART application should include funds for this travel. In the first
year of STAART funding for each center, funding should be requested for an
additional initial meeting of Center Directors and key personnel with NIH
staff to decide on common diagnostic procedures, research tools, and to
implement decision-making processes that are appropriate for the cooperative
agreement mechanism.

USE OF THE COOPERATIVE AGREEMENT MECHANISM

The use of a Cooperative Agreement Mechanism for this RFA is intended to
enhance coordination among STAART Centers in order to increase the impact of
the STAART Centers Program on the public health issues of autism and to
better achieve the goals of the Children's Health Act. The U54 mechanism
implements a process of NIH coordination, guidance, and ongoing evaluation.
For example, it will permit NIH participation in a process of standardizing
diagnostic and other tools across the STAART Centers in collaboration with
the Center Directors and investigators. It will permit awardee and NIH
participation in the Steering Committee (described below) that will make
decisions about collaborative studies that will use the resources of multiple
centers, thus exceeding the capabilities present in any one center.

TERMS AND CONDITIONS OF AWARD

As part of the U54 Cooperative Center Grant process, the following Terms and
Conditions of Award and details of the arbitration procedures pertaining to
the scope and nature of the interaction between the NIH staff and the
participating awardees will be incorporated into the Notice of Grant Award
and provided to the Principal Investigator and the institutional official at
the time of award. These procedures will be in addition to the customary
programmatic and financial negotiations that occur in the administration of
grants.

Cooperative agreements are assistance mechanisms subject to the same
administrative requirements as grants. The special Terms and Conditions of
Award are in addition to, and not in lieu of, otherwise applicable OMB
administrative guidelines, HHS Grant Administration Regulations at 45 CFR
Part 74 and 92, and other HHS, PHS, and NIH grant administration policies and
procedures. Cooperative Agreements are subject to the administrative
requirements outlined in pertinent OMB, HHS, PHS, and NIH guidelines, with
particular emphasis on HHS regulations at 42 CFR Part 52 and 45 CFR Part 74.
Facilities and Administrative Cost (indirect cost) award procedures will
apply to cooperative agreement awards in the same manner as for grants.

The administrative and funding instrument used for this program is a
Cooperative Agreement (U54), 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 it
is 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 awardee(s) for the project
as a whole, although specific tasks and activities in carrying out the
studies will be shared among the awardees and an NIH Science Officer.

Failure of the awardees to meet the performance requirements, including these
special terms and conditions of award, or significant changes in level of
performance, may result in a reduction of budget, withholding of support,
suspension and/or termination of the awards.

1. Awardee Rights and Responsibilities

Awardees have primary authorities and responsibilities to define objectives
and approaches, and to plan, conduct, analyze, and publish results,
interpretations, and conclusions of their studies. The primary
responsibilities of the awardees are to:

o Define the research objectives

o Design the necessary research protocols

o Conduct specific studies

o Analyze and interpret research data

o Propose protocol modifications as required

o Establish an External Consultants Committee to the center

o Participate in STAART collaborative projects approved by the Steering
Committee

o Serve on the STAART Steering Committee

o Agree to sharing of data and biological materials in accordance with
approved data sharing plans

o Agree to participate according to Steering Committee policies in a
centralized data facility that will be established

o Interact with the FDA concerning clinical investigations, when appropriate

o Provide information to the NIH Science Officer and NIH Program Officer
concerning progress

o Maintain career development opportunities to encourage new investigators to
work in the field of autism research

o Abide by all scientific, practical and policy decisions of the Steering
Committee

Awardees will retain custody of and primary rights to their data and
intellectual property developed under the award subject to current government
policies regarding rights of access as consistent with current HHS, PHS, and
NIH policies and subject to the terms and conditions of this RFA.

2. NIH Responsibilities

NIH Science Officers:

NIH Science Officers will be NIH program staff who will have substantial
scientific involvement during the conduct of this activity, through technical
assistance, advice, and coordination above and beyond normal program
stewardship for grants. Each center will have a designated NIH Science
Officer, and a given individual may be the NIH Science Officer for more than
one center. The NIH Science Officers will be selected by the NIH/ACC. The
degree of involvement by the NIH Science Officers will include the following:

o Assist in avoiding unwarranted duplication of effort across centers; help
coordinate collaborative research efforts that involve multiple centers

o Review and comment on critical stages in the research program before
subsequent stages are implemented

o Assist in the interaction between the awardee and the FDA, when appropriate

o Assist in the interaction between the awardee and investigators of other
institutions as well as between the awardee and potential commercial sponsors

o Retain the option of recommending termination of studies if technical
performance falls below acceptable standards, or when specific lines of
research cannot be effectively pursued in a timely manner

o Retain the option to recommend additional research endeavors within the
constraints of the approved research and negotiated budget

o Serve on the STAART Steering Committee

NIH Program Officer:

NIH will appoint a Program Officer who will have program oversight
responsibilities for each center and for the entire STAART Program. This
individual will not be a Science Officer(s). The Program Officer will:

o Have the option to recommend withholding support to a participating
institution if technical performance requirements are not met

o Exercise the normal stewardship responsibilities of an NIH Program Officer

o Carry out continuous review of all activities to ensure objectives are
being met

o Will not be a member of the STAART Steering Committee

3. Data Safety and Monitoring Board

NIH will establish a Data Safety and Monitoring Board (specifics below).

4. Collaborative Responsibilities/Steering Committee

Overall coordination of the Program, consistent with the stated intent of the
RFA, will be done by a Steering Committee consisting of the Directors of each
of the participating centers, the PI of the Data Coordination Center, and NIH
Science Officers. Each Center Director (or designee) will have one vote.
Science Officers may vote, and their total votes will count 1/2 as much as
the total votes of the Center Directors. Center membership on the Steering
Committee becomes effective upon issuance of the Notice of Grant Award. The
Steering Committee may establish additional by-laws, subcommittees, or
workgroups for specific tasks. Science Officers may not chair any committee
or subcommittee. The Steering Committee meetings will be convened at least
once yearly. The purpose of these meetings is to assess scientific progress,
identify new research opportunities, establish priorities, and discuss
strategy. Decisions will be made by a majority vote of a quorum, with an
attempt for consensus when possible. A quorum is the presence of a majority
of the Center Directors and at least one Science Officer. The Steering
Committee can convene through telephone conference or in person. Outside
consultants/experts may be asked to participate in these discussions as
nonvoting advisors. Collaborative projects among the STAART Centers will
require Steering Committee approval. The Steering Committee may also be used
to endorse research instruments that will be used across multiple centers.

Responsibilities of the Steering Committee members include:

o Finalizing collaborative study plans, including design, assessment
instruments, component protocols, and detailed implementation procedures

o Abiding by and directing the study plan for collaborative projects
determined by the Steering Committee

o Monitoring collaborative studies and developing and implementing quality
control procedures

o Conserving grant funds in the service of the common objectives and of the
research plan agreed on by the Steering Committee

o Facilitating the analysis of data and the eventual release to the larger
scientific community (see "Public Domain" below); submitting data on time in
the form and on the schedule determined by the Steering Committee

o Evaluating and reporting study results: defining rules regarding access to
data and publication of findings from analyses of the data set

o Abiding by all scientific, practical, and policy decisions of the Steering
Committee

Any Center Director who considers a Steering Committee decision unacceptable
may appeal by following the arbitration procedure described below.

5. Arbitration Process

When agreement between an awardee and NIH staff or between awardees cannot be
reached on scientific/programmatic issues that may arise after the award is
made, an arbitration panel will be formed. The arbitration panel will
consist of one person selected by the Directors of the Centers, one person
selected by the NIH, and a third person selected by both NIH staff and the
Directors. The decision of the arbitration panel, by majority vote, will be
binding. The special arbitration procedure in no way affects the right of an
awardee to appeal any adverse action in accordance with PHS Regulations at 42
CFR Part 50, Subpart D, and HHS Grant Administration Regulations at 45 CFR
Part 74, section 304, and HHS Regulations at 45 Parts 16 and 75.

6. Public Domain of Data

The data from this cooperative agreement will first be available to be
analyzed and interpreted by the collaborators in the project. However, since
the creation of the data set is funded through public monies and because the
data set will constitute a national scientific resource for the research
community, the awardees will make data of all types available to the larger
research community no more than 24 months from the date after which the final
wave of data for a particular project have been collected and cleaned. More
rapid sharing of data is encouraged.

7. Scientific Advisory Board

The Steering Committee will appoint a Scientific Advisory Board of
independent experts in the research areas represented among the centers.
This board will advise the Steering Committee on the scientific aspects of
STAART activities, including providing review of collaborative studies that
will need to be approved by the Steering Committee before being implemented.

8. Funding of Collaborative Projects

Collaborative projects developed by the Steering Committee will be submitted
to the NIH Program Officer for potential funding after the Steering Committee
has obtained feedback from the Scientific Advisory Board. The Program
Officer will make a final decision based on Steering Group deliberations,
Scientific Advisory Board feedback to the Steering Group, Steering Group
responses to that feedback, and Program Officer consultations with individual
outside experts. The Program Officer may decide to have a collaborative
project submitted by the Steering Group as a competitive supplement that
undergoes NIH-organized peer review prior to the Program Officer's final
decision.

9. Progress Reviews

Progress of the project will be reviewed annually by the NIH Program Officer
at the time each continuation application is considered for funding to assure
that satisfactory progress is being made in achieving the project objectives
and that each site is following the procedures recommended and approved by
the Steering Committee. During the first year of funding, and during
subsequent years, if deemed necessary by the Program Officer, reviews will be
more frequent. Should problems arise in the conduct of the study, the NIH
Program Officer may require that the awardee submit quarterly reports on
progress and fiscal matters. By acceptance of this award, the awardee agrees
to abide by decisions and policies of the project Steering Committee and the
other terms and conditions listed above or referenced in the Notice of Grant
Award.

DATA AND SAFETY MONITORING

It is the policy of NIH that provision be made for the oversight and
monitoring of all intervention studies to ensure the safety of participants
and the validity and integrity of the data. The NIH policy was published in
the NIH Guide to Grants and Contracts, June 10, 1998 and is available at:
http://grants.nih.gov/grants/guide/notice-files/not98-084.html. NIMH
guidance on data safety and monitoring is available at:
http://www.nimh.nih.gov/research/safetymonitoring.cfm. For the STAART
Centers Program, an independent panel of experts, constituting a Data Safety
and Monitoring Board, will be appointed by NIH to monitor safety, quality of
data collection, and integrity of the study. The costs of the DSMB will come
from an NIH source independent of the cooperative agreement.

FREEDOM OF INFORMATION ACT AND DATA

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 (PA) in a public
archive. If so, the application should include a description of the
archiving plan in the study design and include information about this in the
budget justification section of the application. In addition, applicants
should think about how to structure informed consent statements and other
human subjects procedures given the potential for wider use of data collected
under this award.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and
their sub-populations must be included in all NIH-supported biomedical and
behavioral research projects involving human subjects, unless a clear and
compelling rationale and justification are provided indicating that inclusion
is inappropriate with respect to the health of the subjects or the purpose of
the research. This policy results from the NIH Revitalization Act of 1993
(Section 492B of Public Law 103-43).

All investigators proposing research involving human subjects should read the
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in
Clinical Research," published in the NIH Guide for Grants and Contracts on
August 2, 2000
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html);
a complete copy of the updated Guidelines are available at
(http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm). The
revisions relate to NIH defined Phase III clinical trials and require: a)
all applications or proposals and/or protocols to provide a description of
plans to conduct analyses, as appropriate, to address differences by
sex/gender and/or racial/ethnic groups, including subgroups if applicable;
and b) all investigators to report accrual, and to conduct and report
analyses, as appropriate, by sex/gender and/or racial/ethnic group
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS

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

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

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.

REQUIRED EDUCATION IN THE PROTECTION OF HUMAN RESEARCH PARTICIPANTS

All investigators proposing research involving human subjects should read the
policy that was published in the NIH Guide for Grants and Contracts, June 5,
2000 (Revised August 25, 2000), available at the following URL address:
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

NIH GRANTS POLICY STATEMENT

The NIH Grants Policy Statement (NIHGPS) has been revised and reissued. The
provisions of the revised NIHGPS are effective for all funded NIH grants and
cooperative agreements with budget periods beginning on or after March 1,
2001. The revised NIHGPS is available at:
http://grants.nih.gov/grants/policy/nihgps_2001.

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.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT

Applicants may wish to place data collected under this RFA (PA) 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.

LETTER OF INTENT

Prospective applicants are asked to submit, by September 01, 2001, a letter
of intent that includes a descriptive title of the proposed STAART Center and
its projects and cores; the name, address and telephone number of the
Principal Investigator and the names of the project and core leaders; and the
number and title of this RFA. Although this letter is not required, is not
binding, and does not enter into the review of subsequent applications, the
information that it contains allows NIH staff to estimate the potential
review workload to plan the review.

The letter of intent is to be sent to Dr. Steve Foote at the address listed
under INQUIRIES.

APPLICATION PROCEDURES

Applications are to be submitted on the grant application form PHS 398 (rev.
4/98) and will be accepted for the deadline indicated at the beginning of
this document. 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 301/435-0714,
email: GrantsInfo@nih.gov. In addition, the application kits can be found on
the following URL: http://grants.nih.gov/grants/forms.htm.

Applicants are strongly encouraged to call one of the NIH program staff
listed at the end of this document with any questions regarding the
responsiveness of their proposed project to the goals of this RFA.
Applications for the U54 grant are to be prepared in a manner consistent with
the information presented in this RFA. Applicants may also wish to consult
the NICHD U54 Cooperative Specialized Research Center Grant Guidelines,
available from the contacts listed under INQUIRIES below, and at:
http://www.nichd.nih.gov/funding/mechanism/u54_guide.cfm.

SPECIFIC INSTRUCTIONS FOR PREPARING AN APPLICATION

Applications are to be submitted on Form PHS 398
(http://grants.nih.gov/grants/funding/phs398/phs398.html). All instructions
and guidelines accompanying the PHS 398 are to be followed, with the
exception of the sections modified by the specific instructions described
below. Also, applicants can obtain any updated information about preparing
an application at: http://www.nimh.nih.gov/grants/autismcentersrfa.cfm.

In lieu of the preprinted Table of Contents outline on Form Page 3 of PHS
398, a Table of Contents should be prepared listing all of the major sections
described below and paginated to enable reviewers to find specific
information readily.

The Table of Contents should contain the information described below. It
should be divided into the following sections: Section I - General
Information, Section II - Research Plan, and Section III - Appendix. The
following guidelines will provide directions and descriptions for preparing
each section. Major areas to be listed and paginated in the Table of Contents
are underlined.

SECTION I - GENERAL INFORMATION

A. FACE PAGE

Complete all items on the application's face page. This is Form Page 1 of the
application; number succeeding pages consecutively.

On line 2, enter the appropriate Request for Applications (RFA) number and
title, and mark the YES box.

B. DESCRIPTION AND PERSONNEL

On Form Page 2, describe briefly the research program, indicate the emphasis
of the component research projects, and identify the purposes of the proposed
cores.

List key scientific and technical personnel participating in the Center. Use
continuation pages as necessary, numbering consecutively.

C. TABLE OF CONTENTS

Prepare the Table of Contents as noted above. The major areas to be listed
are enumerated in these instructions.

D. BUDGET ESTIMATES

Prepare a series of composite Budget Tables for the center as requested
below. A separate detailed budget is required for each research project and
for each core unit.

1. Composite Budget

a. Use Form Page 4, "DETAILED BUDGET FOR INITIAL BUDGET PERIOD," of the PHS
398 to present the total direct cost budget for all requested support for
the first year. For each category, such as "PERSONNEL," "EQUIPMENT," etc.,
list the amount requested for each research project and for each core unit.

If consortium arrangements have been made involving other institutions or
organizations, include total costs (direct and F&A) associated with such
third party participation in the "CONSORTIUM/CONTRACTUAL COSTS" category.
Costs for purchased services should be itemized under "OTHER EXPENSES."

b. Use Form Page 5, "BUDGET FOR ENTIRE PROPOSED PROJECT PERIOD," of the PHS
398 to prepare a budget, by category, that provides direct cost totals for
each year of requested support.

2.Individual Project and Core Budgets

a. First year (use Form Page 4 of PHS 398 for each)

b. Total project period (use Form Page 5 of PHS 398 for each)

Consortium Budgets (if applicable) should be presented as described in Item 1
(Composite Budget), including a budget for the entire proposed project
period. Total Direct and F & A costs of sub-awardees are to be shown under
"CONSORTIUM/CONTRACTUAL COSTS" on individual research project or core budgets
and a detailed consortium budget is to be inserted following the appropriate
research project or core budgets.

Budget Justifications: Describe the specific functions of key scientific and
technical personnel, consultants, collaborators, and support staff. For all
years, explain and justify any unusual items such as major equipment or
alterations and renovations. For future years of support requested, justify
any significant increases in any category over the first 12-month budget
period. Identify such significant increases with asterisks against the
appropriate amounts.

E. BIOGRAPHICAL SKETCH

Biographical sketches are required for all key scientific and technical
personnel participating in the research projects and core units as listed on
Form Page 2.

Beginning with the Center Director, and following in alphabetical order,
submit biographical sketches as described in the "Instructions for Form PHS-
398," using Form Page 6.

F. SUMMARY OF OTHER SUPPORT

Information regarding active and pending research support of all key
scientific and technical personnel named on Form Page 2 (except consultants)
should be presented in a format such as that suggested in Table I at
http://www.nichd.nih.gov/funding/mechanism/u54_guide.cfm#appendix1, beginning with Center
Director and listed thereafter in alphabetical order. Identify other support
in the following categories:

o Current Active Support
o Applications Pending Review or Funding.

This table is in lieu of the "OTHER SUPPORT" Form Page in PHS 398.

G. RESOURCES

Complete the "RESOURCES" section on Form Page 8 of the PHS 398 for the
overall Center. Briefly describe the features of the institutional
environment that are or would be relevant to the effective implementation of
the proposed program. As appropriate, describe available resources, such as
clinical and laboratory facilities, participating and affiliated units,
patient populations, geographical distribution of space and personnel, and
consultative resources. Use continuation pages as needed.

SECTION II - RESEARCH PLAN

Include a detailed Table of Contents with pagination (numeric only) at
the beginning of Section II. Identify each research project or core unit
by title, and assign each research project a number (I, II, III) and
each core unit a capital letter (A,B,C) that reflects the order in which
the research projects and core units are presented in the application
research plan. For each research project and core unit, provide the name of
the Principal Investigator or Core Director, and biographical sketches for
personnel not identified previously.

A. INTRODUCTORY OVERVIEW (20-page limit)

Provide an overview of the entire proposed center describing the central
theme and goals. Describe how the overall center can achieve its major
objectives. Explain the proposed contribution of each of the projects in
achieving the objectives of the center. Furthermore, the administrative
arrangements and support necessary to effect the research should be carefully
described in the application. Shared resources should be described. In
addition, provide detailed information on collaborations, recruitment,
facilities and resources.

1. Purpose and Objectives of the center. Discuss the philosophy and
objectives of the center and general plans for the proposed grant period.
Discuss the composite research program, highlighting its central theme. List
by title and investigator the component research projects and core
units, showing the interrelationship between the research projects and the
core units and their relationship to the central theme. Describe relevant
history leading up to the center application.

2. Administration, Organization, and Operation of the Center. Include
information on the support and commitment of the parent institution for the
Center, the authority of the Center Director, the use of advisory committees,
and the method of determining core access and space assignment. Describe
organizational framework and provide an organizational chart.

3. Assurances and Collaborative Agreements. Any arrangements for
collaborative and cooperative endeavors or subcontracting should be
highlighted. Letters of Intent to Collaborate and Letters of Agreement from
consultants should be referenced here and included at the end of the
appropriate research project or core unit.

B. PROGRESS REPORT/PRELIMINARY DATA (5-page limit)

This section should be used to present, in condensed form, previously
published and/or preliminary data that are relevant to proposed center
activities and research projects that will be unique to the center and will
involve collaboration across projects and/or cores within the center. Since
individual projects, and preliminary data relevant to them, will be described
in the following section, only those collaborative activities/projects that
bear directly on the proposed center activities should be summarized here.
For ongoing projects or existing cores, list relevant publications published
or accepted for publication during the past five-years. The list of
publications does not count against the page limit.

C. RESEARCH PROJECT DESCRIPTION

Identify each project by a Roman numeral (I, II, III…) and a title.

For each component research project, a full description is to be
provided following the format presented in Form PHS 398. Begin the
presentation of each component research project on a separate cover page. For
each project, include the following information:

1. Introductory Information

a. Indicate:

Project Title

Project Principal Investigator, title, location

Other investigators, consultants, and collaborators, titles (Associate
Professor, Postdoctoral Fellow, student).

b. Abstract of Research Plan (use Form Page 2 of PHS 398)

2. Research Project Plan (Do not exceed 25 pages for Sections a-d):

Discuss the purpose and nature of the project and its relevance to the
application's overall theme. Address the following:

a. Specific Aims

b. Background and Significance

c. Preliminary Studies

d. Research Design and Methods. In addition to usual contents of this
section, describe the research project's use of core unit services, including
need for the services, and the advantages and cost effectiveness of core unit
usage for the project.

e. Human Subjects. For research involving human subjects, this section must
address the inclusion of women, minorities and their subgroups, and children
as research subjects, following relevant policy announcements.

f. Vertebrate Animals

g. Consultants

h. Collaborative arrangements, including pertinent letters of assurance and
intent.

i. Literature Cited

D. CORE DESCRIPTIONS

Identify each proposed core unit by a letter (A, B, C...) and a title
(Administrative, Molecular/Cellular...).

For each core unit, a full description is to be provided following the format
presented below. Do not exceed a total of 25 pages for each core
description.

1. Overall Introduction (Do not exceed 3 pages, excluding the summary table)

Identify the proposed core units by title; briefly summarize the overall
objectives of each core unit; present the organizational framework or chart;
highlight the decision-making process for use of core unit services
described; and present plans for quality control.

Complete a summary table for the first year of the proposed grant by showing
the quantitative use (percent) of each core unit by the component research
projects, presented in a format such as that suggested in Table II (see
below).

Begin the presentation of each core unit on a separate cover page. For each
proposed core, address cost effectiveness and plans for quality control, as
appropriate. For each core, or its equivalent in the center, include the
following information:

2. Administrative Core Unit (if applicable)

a. Objective

b. Staffing: Description of key professional and support staff functions

c. Resources: Description of space and physical resources

d. Services Provided: Describe current and projected services to other core
units and research projects, and the center as a whole

3. Research Core Units

a. Objective

b. Staffing: Brief description of scientific, technical, as well as support
staff functions

c. Resources

d. Administration: Description of overall management of the research core
unit

e. Justification: Description of services provided and their bearing on
productivity and quality, as well as documentation of cost-effectiveness and
quality control

f. Utilization: Indicate past and/or current usage (e.g., assays performed,
animals supplied, etc.) and list projects proposed for core usage, identified
by full title, such as displayed in sample format shown in Table II at
http://www.nichd.nih.gov/funding/mechanism/u54_guide.cfm#appendix1

g. If core service involves human subjects (e.g., recruitment; screening),
discuss the inclusion of women, minorities and their subgroups, and children
as research subjects, following relevant policy announcements (see RFA for
references)

E. CHECKLIST - As required in Form PHS 398

SECTION III - APPENDIX

Include materials as appropriate (see PHS 398).

Other Support and Core Usage information should be provided in the format
shown in sample Tables I and II at
http://www.nichd.nih.gov/funding/mechanism/u54_guide.cfm#appendix1.

SUBMISSION INSTRUCTIONS

Applications must be received by November 29, 2001. Applications not received
as a single package on the receipt date or not conforming to the instructions
contained in PHS 398 (rev. 4/98) Application Kit (as modified in, and superseded
by, the special instructions of this RFA), will be judged non-responsive and
will be returned to the applicant without peer review.

The RFA label and line 2 of the application should both indicate the RFA
number. The RFA label must be affixed to the bottom of the face page.
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. The sample RFA label, available at the following URL:
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified
to allow for this change. Please note this is in Portable Document Format
(PDF).

If the application submitted in response to this RFA is substantially similar
to a grant application already submitted to the NIH for review, but that has
not yet been reviewed, the applicant will be asked to withdraw either the
pending application or the new one. Simultaneous submission of identical
applications will not be allowed, nor will essentially identical applications
be reviewed by different review committees. Therefore, an application that
is essentially identical to one that has already been reviewed cannot be
submitted in response to this RFA. This does not preclude the submission of
substantial revisions of applications already reviewed, but such applications
must include an introduction addressing the previous critique.

Submit a signed, typewritten original of the application, including the
checklist, and 3 signed, exact, single-sided 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 mail or courier service)

At the time of submission, 2 additional copies of the application, including
all appendix material, 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 20892-9663
Bethesda, MD 20817 (for courier/express service)

All applications will initially be assigned to NIMH. Following review, all
of the participating institutes will make decisions about their respective
roles in funding and in the distribution of the responsibilities of NIH
staff. These decisions will be based on the relevance of scientific
activities in specific centers to institute missions and the expertise of NIH
staff.

Applicants from institutions that have a General Clinical Research Center
(GCRC) funded by the NIH National Center for Research Resources may wish to
identify the GCRC as a resource for conducting the proposed research. If so,
a letter of agreement from either the GCRC Program Director or Principal
Investigator should be included with the application.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the CSR and
for responsiveness to this RFA by NIH program staff. 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 NIH in accordance with the review criteria stated below. As
part of the initial merit review, all applications will receive a written
critique and will be discussed, assigned a priority score, and receive a
second level review by the appropriate Institute’s National Advisory Council.

Review Criteria

The criteria to be used in the evaluation of NIH grant applications are
listed below. To put those criteria in context, the following information is
contained in instructions to the peer reviewers.

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

1. Significance. Does this study address an important problem? If the aims
of the application 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
project? Does the applicant acknowledge potential problem areas and consider
alternative tactics?

3. Innovation. Does the project employ novel concepts, approaches or
method? Are the aims original and innovative? Does the project challenge
existing paradigms or develop new methodologies or technologies? Special
emphasis will be placed on integration of basic and clinical research
components relevant to autism into promising synergistic proposals.

4. Investigator. Are the investigators appropriately trained and well
suited to carry out this work?

5. Environment. Does the scientific environment 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 or employ
useful collaborative arrangements? Is there evidence of institutional
support?

The initial review group will also examine: The appropriateness of proposed
project budget and duration; the adequacy of plans to include children and
both genders and minorities and their subgroups as appropriate for the
scientific goals of the research and plans for the recruitment and retention
of subjects; the provisions for the protection of human and animal subjects;
and the safety of the research environment.

Additional Review Criteria Specific to STAART Centers Program

Listed below are additional review criteria to be used in the evaluation of
STAART Center applications; these criteria will be applied to applications by
evaluating preliminary work to organize the center, history of autism
research by the applicants, and plans for implementation of the proposed
program.

Applicants should clearly demonstrate the ways in which the STAART Center
would contribute to the growth of local research programs, support on-going
projects, cooperate with other STAART Centers in collaborative research, and
attract both senior and new investigators to autism research.

A. Center as a Whole

1) The potential for impact of the STAART Center on the progress of autism
research locally and nationally.

2) Extent of "centerness," i.e., does the center as a whole serve a purpose
greater than the sum of the individual components?

3) Effectiveness of the proposed center in meeting the requirements of the
Children's Health Act.

B. Cores

1) How effective is the overall organization of the proposed cores in
relation to the center's total research program?

2) Will each core enhance collaborative and/or interdisciplinary research
within the STAART Center and the wider research community?

3) Would any proposed optional cores duplicate existing resources or
services? If so, are the requested new resources justified?

4) Is the core useful to multiple projects? each core must provide essential
facilities or service for two or more subprojects judged to have substantial
scientific merit.

5) The quality of the facilities or services provided by this core (including
procedures, techniques, and quality control and criteria for prioritization
of usage).

6) The qualifications, experience, and commitment of the personnel involved
in the core.

C. Projects

Projects will be evaluated by the standard NIH criteria listed above and by
their integration into the center and their potential contributions to other
projects in the center.

It should be noted that each meritorious subproject will receive a priority
score and that these ratings will appear in the summary statement. Individual
subprojects judged as "Not Recommended for Further Consideration" (because
the proposed research is not significant and substantial when judged against
the above criteria, or there are other significant concerns) will be deleted
from the center. It is anticipated that inclusion of a 'weak' or 'non-
essential' project in the application will reflect poorly on the overall
program. In addition, NIH retains the right to delete individual projects
when making final funding decisions regarding STAART Center applications, for
example, those that score below the current R01 funding level. It will be
mandatory for each successful application to include at least 3 fundable
research projects. At least one of the fundable projects must be a treatment
study dealing with a topic such as outcome measures, treatment development,
innovative treatment possibilities, effects of pretreatment measures on
treatment selection, treatment efficacy or a similar topic.

D. Data Management

1) Are data management and support procedures developed sufficiently to allow
STAART investigators to access and utilize data, for example, data from the
clinical core? Does the center provide statistical design and support to
STAART investigators?

2) Is there a sound plan to manage and utilize clinical and neuropathological
data? Are adequate safeguards to protect patient confidentiality addressed?
Are staffing, hardware and software adequate?

E. Program Administration

1) Does the PI have the scientific and organizational vision and experience
to serve effectively as the Center Director?

2) Is there evidence of management capabilities for the Center that include
fiscal administration, procurement, property and personnel management,
planning, and budgeting?

F. Facilities

1) Are facilities adequate for the overall functions of the center and to
implement the goals of the STAART Centers Program?

G. Institutional Commitment

1) Is there evidence for institutional commitment to the program, including
provision of funding, space, faculty positions for autism research and other
essential STAART functions, and/or commitments for construction or
renovation?

2) Are the research environment and resources, including equipment and
facilities, adequate? Is there potential for interaction with scientists
from other departments and components?

A site visit is not a required part of the review process. Applicants should
ensure that their written applications are complete and self-contained.

SCHEDULE

Letter of Intent Receipt Date: August 29, 2001
Application Receipt Date: November 29, 2001
Scientific Review Date: March, 2002
Advisory Council Date: May, 2002
Earliest Date of Award: July 01, 2002

AWARD CRITERIA

Funding decisions will be made on the basis of scientific and technical merit
as determined by peer review, program balance, and the availability of funds.

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged. The
opportunity to clarify any issues or questions from potential applicants is
welcome. In addition, the NIH will establish an internet site at:
http://www.nimh.nih.gov/grants/autismcentersrfa.cfm in order to provide
answers to commonly asked questions from potential applicants and to post
points of clarification regarding this RFA.

Direct inquiries regarding programmatic (research scope and eligibility)
issues to:

Steve Foote, Ph.D.
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
Neuroscience Center, Room 7204, MSC-9645
6001 Executive Boulevard
Bethesda MD 20892-9645
For express/overnight services: Rockville, MD 20852
Telephone: (301) 443-3563
Fax: (301) 443-1731
Email: sfoote@mail.nih.gov

Marie Bristol-Power, Ph.D.
National Institute of Child Health and Human Development
6100 Executive Blvd, Room 4B09, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 435-6862
Fax: (301) 480-7773
Email: db171s@nih.gov

Deborah Hirtz M.D.
Clinical Trials, Division of Extramural Research
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard, Room 2212, MSC 9523
Bethesda, MD 20892-9523
Telephone: (301) 496-5821
Fax: (301) 480-1080
Email: dh83f@nih.gov

Judith A. Cooper, Ph.D.
Scientific Programs Branch
Division of Extramural Research
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400C, MSC-7180
Bethesda, MD 20892-7180
Telephone: (301) 496-5061
Fax: (301) 402-6251
Email: Judith_Cooper@nih.gov

Cindy P. Lawler, Ph.D.
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
P.O. Box 12233, MD EC-23
Research Triangle Park, NC 27709
Telephone: (919) 316-4671
FAX: (919) 541-5064
Email: lawler@niehs.nih.gov

Direct inquiries regarding fiscal matters to one of the following:

Bruce Ringler
Grants Management Branch
Division of Extramural Activities
National Institute of Mental Health, NIH
6001 Executive Boulevard, Room 6115, MSC 9605
Bethesda, MD 20892-9605
Telephone: (301) 443-2811
Fax: (301) 443-6885
Email: bringler@nih.gov

Mary E. Daley
Lead Grants Management Specialist, Grants Management Branch
National Institute of Child Health and Human Development
Building 6100, Room 8A17, MSC 7510
Bethesda, MD 20892-7510
Telephone: (301) 496-1305
Fax: (301) 402-0915
Email: md74u@nih.gov

Gladys Melendez-Bohler, M.S.
Grants Management Branch
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard, Room 3290, MSC 9537
Bethesda, Maryland 20892-9537
Telephone: (301) 496-3929
Fax: (301) 402-0219
Email: gb13y@nih.gov

Sara Stone
Chief, Grants Management Branch
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400B, MSC-7180
Bethesda, MD 20892-7180
Telephone: (301) 402-0909
Fax: (301) 402-1758
Email: Sara_Stone@nih.gov

Laura Williams-Boyd
Grants Management Branch
National Institute of Environmental Health Sciences
P.O. Box 12233, MD EC-23
Research Triangle Park, NC 27709
Telephone: (919) 541-7629
FAX: (919) 541-2860
Email: willia27@niehs.nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalogue of Federal Domestic Assistance
Nos: 93.242 (NIMH), 93.865 (NICHD), 93.853 (NINDS), 93.173 (NIDCD), and
93.113 (NIEHS). Awards are made under authorization of Sections 301 and 405
of the Public Health Service Act as amended (42 USC 241 and 284) and
administered under NIH grants policies and Federal Regulations 42 CFR 52 and
45 CFR Parts 74 and 92. This program is not subject to the intergovernmental
review requirements of Executive Order 12372 or Health Systems Agency review.

The Public Health Service strongly encourages all grant and contract
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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