Full Text HD-96-004
NIH GUIDE, Volume 25, Number 14, May 3, 1996
RFA:  HD-96-004
P.T. 34


National Institute of Child Health and Human Development
National Institute on Deafness and Other Communication Disorders
Letter of Intent Receipt Date:  July 1, 1996
Application Receipt Date:  September 20, 1996
The National Institute of Child Health and Human Development (NICHD)
and the National Institute on Deafness and Other Communication
Disorders (NIDCD) invite program project (PO1) grant applications for
research that will elucidate the biological (neurobiologic and
genetic) basis of autism and contribute to the discovery of a
biological and/or diagnostic marker(s) for autism.  Although the
National Institute of Mental Health (NIMH) and the National Institute
of Neurological Disorders and Stroke (NINDS) are not participating in
this Request for Applications (RFA) for Program Projects, NIMH and
NINDS have a long-standing, continuing interest in and financial
commitment to autism research, including focused studies on the
neurobiologic and genetic underpinnings of autistic spectrum
disorders.  NICHD, NIDCD, NIMH, and NINDS autism research programs
support studies using the entire range of available funding
The purpose of this RFA is to provide support for collaborative,
multidisciplinary, methodologically-rigorous programs of research
that will use advanced techniques in biological and behavioral
sciences to study the diagnosis; biological etiology, including
genetics; pathophysiology; and developmental course of autism.  It is
anticipated that up to three program projects will be supported by
NICHD and NIDCD in response to this announcement.
Autism, one of the most common of the developmental disorders, is a
complex disorder of lifelong duration that affects most aspects of
development, learning, and adaptation in the community.  Genetic,
infectious, metabolic, immunologic, neurophysiological, and
environmental causes may lead to similar patterns of altered
development, which result in autism.  Such a complex problem requires
integrated, multidisciplinary, even multisite approaches involving
expertise in a number of disciplines and access to a sufficient
number of well-characterized persons with autism.  Program projects
must have a minimum of three scientifically meritorious, related
research projects. In response to this RFA, applications should
propose an integrated and synergistic program of research on autism
that includes at least one clinical component.  Preference will be
given to applications that include all of the following:  (1) studies
of basic biological (neurobiologic and/or genetic) factors relevant
to the etiology, pathophysiology, developmental course, and/or
treatment outcomes of autism; (2) specific studies of brain function
(e.g., cognitive, information processing, neuropsychological,
electrophysiological, and/or structural and/or functional imaging) in
autism; and (3) studies of changes in phenotypic expression of autism
over time. Multisite, collaborative projects are encouraged as are
studies that specifically address the genetics of autism.
The focus of all program projects funded under this solicitation must
be autism per se.  Other disorders including other autism spectrum
disorders such as Asperger Syndrome (AS), Rett Syndrome (RS),
Childhood Disintegrative Disorder (CDD), and Pervasive Developmental
Disorder Not Otherwise Specified (PDD-NOS) may also be included, but
only if their inclusion clarifies distinctions between autism and
these related disorders.  Other well-defined disorders, which
typically co-occur with autism, e.g., Fragile X, Tuberous Sclerosis,
Attention Deficit Disorder (ADD), may also be included, but only if
they elucidate the nature of autism.  (Also see Special Requirements
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000",
a PHS-led national activity for setting priority areas.  This RFA,
Neurobiology and Genetics of Autism, is related to the Healthy People
2000 priority areas that are concerned with developmental and
learning problems in children and chronic, disabling conditions.
Potential applicants may obtain a copy of "Healthy People 2000" (Full
Report:  Stock No. 017-001-00474-0 or Summary Report:  Stock No.
017-001-00473-1) through the Superintendent of Documents, Government
Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800).
Applications may be submitted by any domestic for-profit and
non-profit organization, public and private, such as a university,
college, hospital, or laboratory, a unit of State and local
government, and eligible agencies of the Federal government.
Applicants may collaborate, through consultation or contractual
arrangements, with domestic and/or international investigators.
Applications from racial and ethnic minority individuals, women, and
persons with disabilities are encouraged.
This RFA will use the NIH program project grant (P01) mechanism.  The
purpose of the P01 mechanism is to encourage multidisciplinary
approaches to the investigation of complex problems like autism and
to facilitate economy of effort, space, and resources.  Applications
should be prepared in a manner consistent with the information
1993), which are available from the NICHD/MRDD office listed under
INQUIRIES.  Responsibility for the planning, direction, and execution
of the proposed program will be solely that of the applicant.  The
total project period for applications submitted in response to this
RFA may not exceed five years.  Anticipated date of award is March 1,
Because the nature and scope of the research proposed in response to
this RFA may vary, it is anticipated that the size of an award will
vary also.
This RFA is a one-time solicitation.  Future competing continuation
applications will compete with all investigator-initiated program
project applications and will be reviewed according to the customary
NICHD peer review procedures.
The following amounts have been set aside for the first year of
support under this RFA:  NICHD, $1,875,000 (total costs) and NIDCD,
$400,000 (total costs).  It is anticipated that up to three awards
will be made. The level of support is dependent on the receipt of a
sufficient number of applications of high scientific merit.  Although
this program is provided for in the financial plan of the respective
institutes, awards pursuant to this RFA are contingent upon the
availability of funds for this purpose.
Autism is a developmental disorder that probably originates during an
early period of brain development. Most, but not all, children with
autism also have mental retardation.  Autism affects an estimated
400,000 Americans with staggering social and public health costs. The
National Institutes of Health (NIH) has been committed to biological
and behavioral research on autism since autism became a diagnostic
entity. Impressive strides have been made in diagnosis and
assessment, in documenting brain differences in autism, in developing
behavioral techniques for intervention, and in assessing the use of
medications to treat some of the learning and behavioral symptoms of
autism. However, at the present time, there is no specific biological
marker for autism, no cure, and no psychopharmacologic treatment for
the core symptoms of the disorder.
In April 1995, the National Institutes of Health (NIH) held an Autism
State- of-the-Science Conference on the NIH campus.  A working group
of distinguished scientists in autism and related areas, and parent
representatives met to assess the state of the science in autism,
identify gaps in knowledge, and make recommendations to the NIH
regarding promising areas for future research. The National Institute
of Child Health and Human Development (NICHD) served as the lead
agency for this conference which was cosponsored by the National
Institute on Deafness and Other Communication Disorders (NIDCD), the
National Institute of Mental Health (NIMH), and the National
Institute of Neurological Disorders and Stroke (NINDS).  The report
from that conference (Preliminary Report to the National Institutes
of Health from the Autism Working Group) contained recommendations
regarding research needs in diagnosis/ classification, epidemiology,
pathophysiology including etiology and brain mechanisms,
communication and social development, and medical and
social/behavioral intervention.  In addition, the conference
attendees repeatedly cited the need for methodological refinements
and multidisciplinary research strategies to identify a biological
and/or diagnostic marker(s) for autism.  More than 700 copies of the
preliminary report were distributed to scientists and others for
comment.  Those comments were incorporated into the final report
(Report to the National Institutes of Health on the State-of-the-
Science in Autism, in press. For a copy, contact NICHD, MRDD office
listed under INQUIRIES below).  Particularly clear from the report
and from comments from the field is the need for multi-site,
collaborative studies that draw on expertise from many disciplines.
This RFA represents the NIH's long-standing commitment to autism as
well as NICHD's and NIDCD's specific response to the research
recommendations and concerns raised in the final report from the NIH
Autism State-of-the-Science conference.
Research Focus
This RFA invites investigators to apply advanced techniques of
diagnosis and assessment, population genetics and molecular biology,
structural and functional brain imaging, animal models, behavioral
and cognitive neuroscience, and focused interventions, to elucidate
the neurobiology of autism, with the long term goal of effective
diagnosis, treatment, and prevention.  Of particular interest are
studies of persons with autism who are well-defined in terms of age,
age of onset, gender, ethnicity, socioeconomic status (SES), severity
of autism, comorbid conditions, intellectual status,
cognitive-linguistic status, neuropsychological and
neurophysiological status, educational status, and social/behavioral
competencies.  The following research priorities are offered as
examples of areas of particular interest to the participating
institutes.  Preference in funding will be given to integrated,
synergistic, multidisciplinary program projects that include all of
the following: (1) studies of basic biological (neurobiological
and/or genetic) factors relevant to the etiology, pathophysiology,
and/or developmental course of autism; (2) specific studies of brain
structure and/or function (e.g., cognitive, information processing,
neuropsychological, electrophysiological, or structural and/or
functional imaging) in autism; and, (3) studies of changes in
phenotypic expression over time.  (Also see Special Requirements
Available evidence indicates that the initial brain abnormalities in
autism may occur during the early period of brain development.
Various possible causes (e.g., infectious, metabolic, immunological,
neurophysiological, environmental) may lead to similar patterns of
development that result in autism.  There is increasing evidence,
however, that autism may be one of the most strongly genetically
based of the complex developmental disorders.  This genetic
susceptibility probably involves more than one gene and may differ
across families.  Research is needed to elucidate the genetic basis
for and/or contributions to the etiology of autism.
Research is encouraged in, but not limited to, the following genetic
o  Gene mapping studies to identify the specific genetic loci that
contribute directly to autism;
o  Development of useful animal models based on mutations of
candidate genes, particularly genes regulating neurotransmitter
o  Studies of genomic control and regulation of neural development
particularly relevant to autism;
o  Studies that elucidate gene-environment interactions;
Brain Structure and Function
Contemporary electrophysiological and imaging research, coupled with
sophisticated neuropsychologic tools, offer exciting research
possibilities for noninvasive study of brain structure and function
in vivo, particularly as new technology in both image acquisition and
image analysis is developed. Taken together, the available evidence
in autism suggests that, although certain aspects of brain
functioning are often spared in autism, the disorder involves
multiple structures at multiple levels of the neuraxis.  As with all
research in autism, standardized diagnosis and control for age, age
of onset (congenital vs regression), gender, degree of mental
retardation, language and co-morbid conditions are essential in
interpreting these findings.  The identification of reliably
occurring subtypes and subgroups will be absolutely critical with all
methodologies, as a variety of brain structures and mechanisms may
exist for subtypes with different etiologies.
Applications are encouraged in, but not limited to, the following
o  Hypothesis-driven studies combining imaging and neuropsychologic
methods that demonstrate specific and predictable changes in the
relationships between measurements of structure and function in
different regions of the brain over the course of development,
especially as they relate to executive function, attention, and
memory in autism;
o  Systematic investigations that use in vivo and in vitro
methodologies to elucidate the pathophysiology of autism;
o  Research on brain mechanisms (e.g., structural, functional,
electrophysiological and/or neurochemical) underlying the
development, regulation, and modulation of behaviors characteristic
of autism, particularly those involving communication, social
interaction, sensory problems, and/or movement in autism;
o  Studies that elucidate structural and/or functional differences:
a) between children with congenital and later-onset autism, and/or b)
that have the potential to explain or predict loss of language or
seizure-prone or seizure-free patients;
o  Longitudinal studies of nerve growth and nerve growth migratory
substances important for the modeling and remodeling of basic
architectonics of the human brain, which have particular relevance to
o  Research on the neurobiologic basis for reported abnormalities in
motor and sensory abilities, particularly as they relate to
comprehension and communicative expression, and/or to related
research in movement and synchrony;
o  Studies of the role of immune factors in autism;
o  Hypothesis-driven studies of the role of neurotransmitters in
o  Neurochemical markers for autism.
Diagnosis and Classification
For the first time, there are consistent criteria for the diagnosis
of autism spectrum disorders in both the American (DSM-IV, 1994) and
international (ICD- 10, 1993) diagnostic systems.  The precision of
these definitions will continue to evolve as new research clarifies
the phenotype of autism.  Autism remains one of the most reliable
diagnoses in developmental and psychiatric research, although the
validity of the definitions in terms of onset, course, or response to
treatment remains to be established. Definitions of Asperger Syndrome
(AS), Rett syndrome (RS), Childhood Disintegrative Disorder (CDD),
and Pervasive Developmental Disorder Not Otherwise Specified
(PDD-NOS) yielded clear distinctions from autism in the DSM-IV field
trials and other studies. Standard measures that yield these
diagnoses across the age span from three years to adulthood are now
available and widely used in research in North America and Europe.
Subject Selection criteria outlined below are applicable for research
in this area.  Age of onset (congenital vs regression) has particular
relevance for early identification.
Recommended areas of investigation include, but are not limited to
the following:
o  Longitudinal, developmental studies of diagnosis and
classification, combined with biological and behavioral studies that
establish the validity of the similarities and distinctions across
two or more of the autism spectrum disorders with respect to such
characteristics as onset, developmental course, response to
treatment, and/or outcome.  Autism can be distinguished reliably from
Rett syndrome, and Childhood Disintegrative Disorder (CDD), but are
these simply different expressions of the same disorder or of
different disorders with different etiologies, course, and/or
treatment response?  The search for a biological/diagnostic marker(s)
is critical here.
o  Studies of other subgroups within autism that have been replicated
across independent centers and across time and that address
significant aspects of diagnosis such as course, response to
treatment, and/or well-defined differences in etiology,
pathophysiology, and behavioral repertoire;
o  Research on additional behavioral or developmental features often
observed in autism, e.g., sensory hypersensitivity or repetitive or
stereotyped behaviors, as well as features that may represent
separate, but co- occurring (comorbid) disorders, e.g.,
obsessive-compulsive disorder or epilepsy as these occur in autism;
o  Research on the reliability and validity of current diagnosis and
assessment systems for children with autism who are from racially
and/or ethnically diverse backgrounds;
o  Studies that establish screening and/or diagnostic criteria for
very young (under three years) children with autism.  Early
identification and prescription of specialized services is hampered
by the lack of reliable and valid screening as well as diagnostic
o  Studies that allow more accurate description of adults with
autism, particularly those that address issues in the transition from
school to work and/or follow up of higher functioning individuals
into adulthood.
Communication/Social/Emotional Development
Autism is a disorder characterized by significant impairment in both
verbal and nonverbal communication, deficits in emotional expression
and understanding, difficulties in initiating and maintaining social
interaction, and a limited behavioral repertoire with restricted
interests and activities. There are few longitudinal data so the
course of communicative, social, and emotional development in
children with autism is poorly understood.  If longitudinal studies
in communication, social, and/or emotional development are combined
with biological studies, such research can elucidate the interplay
over time between biological and environmental factors that influence
the onset and course of lifespan communicative and social competence.
Areas of research may include, but are not limited to the following:
o  Longitudinal, developmental studies of behaviors that are
precursors to later communicative, social, and emotional behaviors,
e.g., imitation, joint attention and joint referencing, vocalization,
gaze, attachment, play, compliance, and self-awareness, particularly
if studied in tandem with possible underlying neurobiological
o  Subtle sensory and motor impairments in autism that impact on
social interaction and communication;
o  Predictors of which children will ultimately develop expressive
language and of which will lose expressive language (which occurs in
up to one third of children who develop autism after apparently
normal early development);
o  Development, functions, and treatment of unconventional verbal
behaviors such as echolalia, perseverative language, and incessant
questions, particularly in the context of underlying neurobiology;
Medical and Psychosocial Intervention
Although both behavioral and medical interventions are available to
improve learning and behavior in autism, there is no evidence of a
cure for autism, nor any psychopharmacological treatments for the
core symptoms of autism. Both basic research and clinical studies
suggest the importance of intensive, structured, and highly
individualized treatment for autism.  Interventions early in life may
be particularly effective, presumably because of the plasticity of
the brain at that time.  People of all ages, however, can profit from
individualized treatment, although it is unclear at this time what
specific components of treatment "packages" are responsible for gains
noted. Further, the majority of intervention research has been
conducted by the originator of the methods, or by someone with vested
interests in the methods under study.  Focused, single subject or
group design studies are needed to advance understanding of the
opportunities for and limits to which developmental neuroplasticity
allows for recovery with intervention.
This RFA is seeking focused, theory-driven, experimental
interventions targeted at abilities or deficits specifically
deficient in autism and/or predictive of later language and social
skills.  Baseline and outcome biological, cognitive, and
social/communicative functioning can be assessed and progress
monitored.  Interventions should be consistent with one or more of
the biological hypotheses being tested in other subprojects of the
RFA. Such research may include, but is not limited to:
o  New approaches to treatment utilizing advances in neuroscience,
genetics, immunology, or other neurobiologic, electrophysiological,
behavioral, and pharmacologic fields;
o  Focused interventions that test specific theories or hypotheses
regarding possible neurobiological mechanisms;
o  Design and evaluation of pharmacologic agents specifically for the
core symptoms of autism and/or that are useful in differentiating
subtypes in autism;
o  Essential vs non-essential components of treatment "packages" for
specific subtypes of clients;
o  Generalizability of subject change across situations or
environments and/or generalizability of the method across
o  Interaction of persons with autism with specific aspects of their
environments that typically affect child outcome.  Needed are studies
of parent-child and sibling-sibling interaction over time, and of the
effects of physical environments, behavioral modeling, relationships,
and exposure to language models that could contribute to more or less
successful outcomes, carried out in concert with relevant
neurobiological studies.
Clinical Component(s).  All funded projects must include at least one
clinical component.
Annual Meetings:  Principal Investigators from funded program
projects are expected to attend an annual meeting at the NIH to share
findings, research approaches, and core instrumentation.  The first
such meeting is expected to take place in March 1997.  Provision for
funds for travel to this annual meeting should be included in the
budget and budget justification.
Advisory Board:  Applicants are encouraged to propose and design an
external Advisory Board to provide outside counsel and review for the
program project. Applicants are not to select or contact proposed
Advisory Board members at this time.  Details of the operation of the
Board, including size, structure, function, and frequency of meetings
should be specified, as well as the type of expertise and level of
seniority of Board members to be recruited.  Members of the Advisory
Board are to be selected and confirmed within three months of the
award date and notification sent to program staff. Names of
prospective Board members are not to appear in the application or
appendices.  Provision for costs of the Advisory Board are to be
included in the budget and budget justification.
Research Population:  The selection of the core research population
should be based upon the need to conduct integrated, prospective,
developmental, longitudinal investigations incorporating biomedical
and behavioral studies. Well-justified, cross-sectional studies
should also be considered.  Such cross-sectional studies must be
related meaningfully to the questions being asked within the
longitudinal studies.
It is expected that not all children within the research population
will manifest the entire range of characteristics of autism.  In
fact, it is likely that there will be subgroups and subtypes of
subjects with significantly different patterns of strengths and
deficits, different patterns of comorbidity, levels of severity, and
different psychological/cognitive profiles.  Applicants, then, should
consider research protocols that are capable of identifying
well-defined subgroups and subtypes that exist within the sample.
Investigators should also consider a broad enough sample to ensure a
representative number of subtypes and contrast groups within the
study population.  For example, of interest are subtypes of children
with autism who display no comorbid conditions, a single comorbid
condition, or a combination of comorbid deficits, e. g., deficits in
intellectual functioning and attention.
Access to Subjects:  Applicants must document access to a sufficient
number of well-characterized subjects with autism.
Subject Selection Criteria:  The samples for study must be rigorously
defined so that complete replication in another site can be
accomplished.  Within this context, applicants should provide clearly
documented and operationalized definitions for their subject
selection criteria.  Investigators are expected to use standard
diagnostic procedures that operationalize DSM-IV/ICD 10 criteria in
order to promote replicability and encourage communication among
scientists, clinicians, and parents.  Identification of autism on the
basis of a criterion of "school identified" or "clinic identified" is
discouraged unless clearly identified diagnostic criteria in these
cases match the applicant's a priori established selection criteria.
Likewise, criteria for selection of contrast group(s) must be clearly
specified and justified.
All patient participants selected for study must be defined with
reference to age, age of onset (congenital vs. regression), gender,
ethnicity, socioeconomic status (SES), severity of autism, comorbid
conditions, intellectual, cognitive, and linguistic status.  As far
as possible, comparison groups should be comparable on most of these
characteristics and comparison norms should take into account age,
ethnicity, and gender.  Failure to control for such variables is one
reason why replication rates of previous studies, especially
biomedical studies, are so low.  Use of structured instruments for
assessment of current and past history of neurologic and psychiatric
disorders and family history is strongly encouraged.
Measurement Criteria:  Standardized tests, laboratory tasks,
observational measures, and other assessment procedures (e.g.,
dynamic assessment procedures) should be selected on the basis of
known reliability and validity as well as appropriateness to the
population under study.  If reliability and validity characteristics
are not yet known for a particular assessment or measurement
procedure, the application should contain specific plans for
establishing these features.  The valid measure of change over time
will be critical to much of the research called for in this RFA since
the study of developmental course is one of the primary concerns.
Statistical Methodologies:  New statistical methodologies are
currently emerging to make longitudinal studies more informative.
Models such as individual growth curve models acknowledge consistent
individual differences expressed in different trajectories. To reduce
both the time and cost of longitudinal studies, investigators are
encouraged to investigate accelerated lifetime sampling or other
available methods, where subjects are entered into study at different
ages and followed for some period of time, in such a way that age
spans over which subjects are followed overlap each other.
Investigators are encouraged to explore these and other
cost-effective strategies that are particularly appropriate to the
study of this disorder.
Gene Mapping Studies:  Program projects proposing a gene mapping
component must include documentation of access to a large enough
sample of well- characterized subjects.  For genetic linkage of
complex disorders of this sort, a variety of factors, e.g., genetic
heterogeneity, subtypes etc., will affect the power of a linkage
analysis.  This necessitates very large samples to allow detection of
genetic effects.  Successful applicant teams must have relevant
training and experience in diagnosis and classification in autism for
definition of the phenotype, as well as training and experience in
genetics. Applicants are encouraged to become familiar with the
resources available at NIH for genotyping and for consultation
regarding genetic analysis and statistical genetics.  Multisite
collaborative teams may be needed to encompass the necessary
expertise and to have documented access to a large enough sample of
well-characterized cases.
It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH-supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification are
provided that inclusion is inappropriate with respect to the health
of the subjects or the purpose of the research.  This new policy
results from the NIH Revitalization Act of 1993 (Section 492B of
Public Law 103-43) and supersedes and strengthens the previous
policies (Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations), which
have been in effect since 1990.  The new policy contains some
provisions that are substantially different from the 1990 policies.
All investigators proposing research involving human subjects should
read the NIH Guidelines for Inclusion of Women and Minorities as
Subjects in Clinical Research, which have been published in the
Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted
in the NIH Guide for Grants and Contracts, Volume 23, Number 11,
March 18, 1994.
Investigators also may obtain copies of the policy from the program
staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.
Prospective applicants are asked to submit, by July 1, 1996, a letter
of intent that includes a descriptive title of the proposed research;
the name, address, telephone, fax, and, if available, e-mail numbers
of the overall program project Principal Investigator; titles and
principal investigators of the component subprojects and cores; names
of other key personnel and participating institutions; a statement of
relevance of the project to autism; and the number and title of the
RFA in response to which the application may be submitted.
Although a letter of intent is not required, is not binding, and does
not enter into the review of a subsequent application, the
information that it contains allows Institute staff to estimate the
potential review workload and to avoid possible conflict of interest
in the review.
The letter of intent is to be sent to:
Marie M. Bristol, Ph.D,
Center for Research for Mothers and Children
National Institute of Child Health and Human Development
Executive Building, Room 4B09
6100 Executive Boulevard MSC 7510
Bethesda, MD  20892-7510
Rockville, MD  20852-7510 (for express/courier service)
Telephone:  (301) 496 1383
FAX:  (301) 496 3791
Applications are to be submitted on grant application form PHS 398
(rev. 5/95) and will be accepted only at the announced deadline.
Applications kits are available at most institutional offices of
sponsored research and may be obtained from the Grants Information
Office, Office of Extramural Outreach and Information Resources,
National Institutes of Health, 6701 Rockledge Drive, MSC 7910,
Bethesda, MD 20892-7910, telephone 301/710-0267, email:
ASKNIH@odrockm1.od.nih.gov. Applications should be prepared in a
manner consistent with the information presented in NICHD PO1 PROGRAM
PROJECT GUIDELINES, (rev. Nov 1993), which are available from the
MRDD, CRMC, NICHD office listed under INQUIRIES.
The RFA label available in the PHS 398 (rev. 5/95) application form
must be affixed to the bottom of the face page of the application.
Failure to use this label could result in delayed processing of the
application such that it may not reach the review committee in time
for review.  In addition, the RFA title and number must be typed on
line 2 of the face page of the application form and the YES box must
be marked.
Submit a signed, typewritten original of the application, including
the Checklist, and three signed, photocopies in one package to:
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC-7710
BETHESDA, MD 20892-7710
BETHESDA, MD  20817 (for express/courier service)
At the time of submission, two additional copies of the application
must also be sent under separate cover to:
Susan C. Streufert, Ph.D.
Division of Scientific Review
National Institute of Child Health and Human Development
Executive Building, Room 5E03
6100 Executive Boulevard MSC 7510
Bethesda, MD  20892-7510
Rockville, MD  20852-7510 (for express/courier service)
Applications must be received by September 20, 1996.  If an
application is received after that date, it will be returned to the
applicant without review.  The Division of Research Grants (DRG) will
not accept any application in response to this RFA that is
essentially the same as one currently pending initial review, unless
the applicant withdraws the pending application.  The DRG will not
accept any application that is the same as one already reviewed.
This does not preclude the submission of substantial revisions of
applications already reviewed, but such applications must include an
introduction addressing the previous critique.
Upon receipt, applications will be reviewed for completeness by DRG
and then reviewed for responsiveness to the RFA by NICHD and NIDCD
staff.  Incomplete applications will be returned to the applicants
without further consideration.  If the application is not responsive
to the RFA, DSR staff may contact the applicant to determine whether
to return the application to the applicant or to submit it for review
in competition with unsolicited applications at the next review
Applications that are complete and responsive will be evaluated for
scientific and technical merit by an appropriate peer review group
convened by the NICHD in accordance with the standard NIH peer review
procedures.  As part of the initial merit review, all applications
will receive a written critique and undergo a process in which only
those applications deemed to have the highest scientific merit,
generally the top half of applications under review, will be
discussed, assigned a priority score, and receive a second level
review by the National Advisory Council(s) of NICHD and/or NIDCD.
Review Criteria
Review criteria for RFAs are generally the same as those for
unsolicited program project grant applications.  The scientific,
technical, or medical significance and originality of the overall
program and of the individual projects are the most critical elements
in the review.  In addition, applications received in response to
this RFA will be evaluated according to the following criteria:
Overall Program Criteria
o  documentation of the ability to recruit and maintain a sufficient
number of well-characterized participants with autism;
o  coordination, interrelationship, cohesiveness, and synergism among
the individual research projects and core components; relationship of
the program objectives to autism; evidence that the proposed program
project will have greater significance as a whole than the individual
projects standing alone;
o  relevance of the program to the NICHD mission, and/or to the
mission of NIDCD;
o  likelihood that this research will contribute to the discovery of
a biological/diagnostic marker(s) for autism;
o  the leadership ability, scientific stature, and administrative
competence of the program director, including appropriate commitments
of time and direction;
o  demonstration of the program director's ability to develop a
well-defined central research theme for the overall program project;
o  participation of a suitable number of responsible, experienced
investigators who have well-designed research projects;
o  previous experience of participating investigators in
collaborative research, preferably with a prior history of
collaborative scholarly productivity;
o  an appropriate organizational and administrative structure for
effective attainment of program objectives, including specific
procedures for both regular and extraordinary scientific and fiscal
communication, collaboration, and cooperation among project
investigators within and across projects and sites;
o  arrangements for internal quality control of ongoing research, the
allocation of funds, day-to-day management, and contractual
o  the quality of the intellectual and physical environment in which
the research would be conducted, including the availability of space,
equipment, human subjects, and other resources, and the potential for
interaction with scientists from multiple departments, institutions,
and with internal and external advisory committees;
o  the appropriateness of the program size; small enough to afford
effective interaction focused on a specific central theme and large
enough to achieve synergy and economies not provided by regular
research grants;
o  institutional commitment to the research and to the program
including fiscal responsibility and management capability to assist
the program director and staff in adhering to NIH policies;
o  qualifications and research experience of the overall Program
Director for the entire program project, and of the principal
investigators for the component projects;
o  for multisite projects, evidence that the multiple sites make
substantial contributions to the scientific enterprise in a
cost-effective manner, e.g., range of scientific expertise, access to
well-characterized subjects, and/or additional institutional
Individual Projects and Core Unit Criteria:
The review criteria for the component research projects and core
units are:
o  the scientific merit and relevance to autism of each individual
project in the program context;
o  sufficient pilot data to support the feasibility and scientific
merit of each subproject, if appropriate;
o  qualifications, experience, and commitment of the investigators,
and their ability to devote the required time and effort to the
o  appropriateness and adequacy of the experimental approaches
proposed to carry out the research;
o  the multidisciplinary scope of the program;
o  the specific scientific objectives of each project that will
benefit from, depend upon, or contribute to collaborative
interactions with the other component projects within the PO1, even
if the component projects are located at different sites (i.e.,
objectives that can be uniquely accomplished, specific contributions
to the accomplishments of objectives in other projects, objectives
that can be accomplished with greater effectiveness, and/or economy
of effort, etc.);
o  appropriateness of the proposed budget for each component research
project and core unit, and duration in relation to the proposed
research; cost effectiveness and quality control of core services;
o  quality of and justification for proposed core facilities and the
appropriateness of the research projects' use of core services;
o  specific plans to enhance communication, cooperation, and
collaboration among the investigators;
o  as appropriate, adequacy of plans for the protection of human
subjects, animals, and/or the environment; and
o  for all human subject research, the appropriateness of study
samples in terms of adequate representation of women and minorities.
In addition to the scientific and technical merit of the application
as determined by peer review, other factors may be considered in
making the awards.  These criteria are:
o  clear relevance of each subproject to the biology and behaviors of
o  scientifically appropriate, novel approaches to autism research;
o  use of multiple levels of analysis to address autism including
etiology, neurobiology; pathophysiology; and/or treatment in autism
within a single program project;
o  inclusion of diagnostic, neurobiological and/or genetic, imaging,
and intervention studies on a common sample (or subsample of the
total sample).
o  relevance to national needs, NIH Institute priorities, portfolio
balance, and geographic distribution.  The anticipated date of the
award is March 1, 1997.
Inquiries concerning this RFA are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.
Direct inquiries regarding programmatic and scientific issues to:
Marie M. Bristol, Ph.D.
Center for Research for Mothers and Children
National Institute of Child Health and Human Development
Executive Building, Room 4B09 - MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-1383
FAX:  (301) 496-3791
Judith Cooper, Ph.D.
Division of Human Communication
National Institute on Deafness and Other Communication Disorders
Executive Plaza South, Room 400C-11 - MSC 7180
Bethesda, MD  20892-7180
Telephone:  (301) 496-5061
FAX:  (301) 402-6251
For fiscal and administrative inquiries, potential applicants may
Mr. E. Douglas Shawver
Grants Management Branch
National Institute of Child Health and Human Development
Executive Building, Room 8A017
6100 Executive Boulevard MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496 1303
This program is described in the Catalog of Federal Domestic
Assistance No. 93.865, Research for Mothers and Children.  Awards are
made under authorization of the Public Health Services Act, Title IV,
Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC
241 and 285) and administered under PHS grants policies and Federal
Regulations 42 CFR 52 and 45 CFR Part 74.  This program is not
subject to the intergovernmental review requirements of Executive
Order 12372 or Health Systems Agency review.
The PHS 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.

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