RESEARCH ON AUTISM AND AUTISM SPECTRUM DISORDERS

RELEASE DATE:  April 2, 2004

PA NUMBER:  PA-04-085

January 3, 2007 - Effective with the February 5, 2007 submission date, 
all R01 applications must be submitted through Grants.gov using 
the electronic SF424 (R&R) application. Accordingly, the R01 portion 
of this funding opportunity expires on January 3, 2007.  Unsolicited 
or investigator-initiated R01 electronic SF424 (R&R) applications may 
be submitted through the Research Project Grant (Parent R01) announcement.

March 2, 2006 (NOT-OD-06-046) – Effective with the June 1, 2006 submission date, 
all R03, R21, R33 and R34 applications must be submitted through Grants.gov using 
the electronic SF424 (R&R) application. This announcement will stay active for 
only the May 1, 2006 AIDS and AIDS-related application submission date for these 
mechanisms. The non-AIDS portion of this funding opportunity for these mechanisms 
expires on the date indicated below. Other mechanisms relating to this announcement 
will continue to be accepted using paper PHS 398 applications until the stated 
expiration date below, or transition to electronic application submission. 
Replacement R03 (PA-06-391) and R21 (PA-06-392) funding opportunity announcements 
have been issued for the submission date of June 1, 2006 and submission dates 
for AIDS and non-AIDS applications thereafter.

EXPIRATION DATE for R03 and R21 Non-AIDS Applications: March 2, 2006
EXPIRATION DATE for R03 and R21 AIDS and AIDS-Related Applications: May 2, 2006 
EXPIRATION DATE for R01 Non-AIDS Applications: November 2, 2006
EXPIRATION DATE for R01 AIDS and AIDS-Related Applications: January 3, 2007

Department of Health and Human Services (DHHS)

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

COMPONENTS OF PARTICIPATING ORGANIZATION:
National Institute of Mental Health (NIMH)
 (http://www.nimh.nih.gov)
National Institute on Deafness and Other Communication Disorders (NIDCD)
 (http://www.nidcd.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 of Environmental Health Sciences (NIEHS)
 (http://www.niehs.nih.gov)
National Institute of Nursing Research (NINR)
 (http://www.ninr.nih.gov)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.113, 93.115, 93.173, 93.242, 
93.361, 93.865, 93.853

THIS PA CONTAINS THE FOLLOWING INFORMATION

o  Purpose of the PA
o  Research Objectives
o  Mechanism(s) of Support
o  Eligible Institutions
o  Individuals Eligible to Become Principal Investigators
o  Special Requirements
o  Where to Send Inquiries
o  Submitting an Application
o  Supplementary Instructions
o  Peer Review Process
o  Review Criteria
o  Award Criteria
o  Required Federal Citations

PURPOSE OF THIS PA

This PA replaces PA-01-051.

The purpose of this program announcement is to encourage grant applications for 
the support of research designed to elucidate the diagnosis, epidemiology, 
etiology, genetics, treatment, and optimal means of service delivery in relation 
to Autistic Disorder ("autism") and autism spectrum disorders (Rett's Disorder, 
Childhood Disintegrative Disorder, Asperger's Disorder, Pervasive Developmental 
Disorder-Not Otherwise Specified, or "Atypical Autism").

This PA is meant to support the broad research goals of the Autism Research 
Matrix (http://www.nimh.nih.gov/autismiacc/researchmatrix.pdf).  
In February 2003, Congress requested that the Department of Health and Human 
Services (HHS) develop a set of autism research goals and activities for the 
next several years (House Report 109-10).  Input into this activity included a 
meeting of autism investigators with a range of scientific expertise, as well 
as input from community members.  Preparation for specifying this matrix 
involved a two-day meeting of an expert panel of scientists; public 
presentation and discussion of a draft matrix at the Autism Summit Conference 
in Washington DC on November 20, 2003; and adoption of the matrix by the 
Federal Interagency Autism Coordinating Committee (IACC).

RESEARCH OBJECTIVES

Current classification systems (e.g., DSM-IV) include five separate diagnoses under 
the Pervasive Developmental Disorders:  Autistic Disorder, Rett's Disorder, 
Childhood Disintegrative Disorder, Asperger's Disorder, and Pervasive Developmental 
Disorder Not Otherwise Specified.  Collectively, these Pervasive Developmental 
Disorders are often referred to as “Autism Spectrum Disorders”.  These disorders 
share a cluster of impairments in reciprocal social interaction and communication 
and/or the presence of stereotyped behavior, interests, and activities.  These 
complex disorders are usually of lifelong duration and affect multiple aspects of 
development, learning, and adaptation in the community, and thus represent a 
pressing public health need.  The etiologies of these disorders are poorly 
understood, but are thought to include genetic, metabolic, immunologic, or 
infectious or other environmental influences.

Clinical research involving these disorders requires well-integrated, multi-
disciplinary, methodologically-rigorous scientific approaches and access to a 
sufficient number of well-characterized patients with these disorders.  Basic 
research into the pathophysiology of autism and autism spectrum disorders, 
including research on brain mechanisms and genetics, is of special interest.  Also 
of high priority are clinical and applied investigations that may lead to the 
development of diagnostic research instruments, treatments, and intervention 
strategies.  Specific areas of interest thus include epidemiology, early 
identification and diagnosis, genetic studies, brain mechanisms, communication 
skills, cognitive neuroscience, psychosocial (behavioral) interventions, 
pharmacological and other biological interventions, and support and rehabilitative 
services across the life-span, including adulthood and the transition to adulthood.

Areas of interest include, but need not be limited to, the following:

o  Epidemiology:  Studies of the genetic and environmental epidemiology of autism 
to determine risk and protective processes in the etiology of autism, including 
environmental exposures during pregnancy and early childhood; longitudinal studies 
of high-risk populations; epidemiologic research on interactive genetic and 
environmental processes that increase or decrease risk for autism; research on the 
expression of the full range of autism spectrum disorders; studies of their 
developmental course across the life-span; studies that characterize the range of 
expression within families; and research on co-occurring features, especially 
research that characterizes and quantifies risk and protective processes associated 
with co-occurrence.  Also of interest are clinical epidemiologic studies of autism 
spectrum disorders in clinical settings, including studies of clinical decision-
making in personal-encounter care for individuals and families.

o  Screening, Early Identification, and Diagnosis:  Key diagnostic and phenotypic 
features associated with various stages of development; development of new 
screening tools for use in a variety of settings; assessment of comorbid features 
including hyperactivity, attentional dysfunctions, epilepsy, and obsessive and 
compulsive symptoms; the creation of new measures to be used in longitudinal 
studies and measures that further differentiate the subtypes of autism spectrum 
disorders; and, developmental factors relevant to reliable and valid diagnosis.

o  Genetic Studies:  Family-based association analysis and other linkage 
disequilibrium approaches that aim to identify specific susceptibility genes; 
studies of epigenetic mechanisms and long range control of gene expression; high-
resolution mapping and positional cloning studies; resolution of locus 
heterogeneity; analysis of the interaction of autism susceptibility genes with 
environmental exposures and/or genes responsive to environmental insult; testing 
for potential candidate genes.  An area of particular interest is the effect of 
genetic factors on therapeutic drug response in autistic individuals (see 
Pharmacogenomics, below).

o  Brain Mechanisms:  Studies of brain mechanisms underlying the development, 
regulation, and modulation of behaviors characterizing autism and autism spectrum 
disorders, particularly those mechanisms involving communication and social 
interaction; studies of brain mechanisms and biological factors underlying autistic 
regression, or the loss of previously acquired skills; studies of brain mechanisms 
involved in the development of abnormal electroencephalograms and epilepsy and 
studies to clarify the subtypes of seizures and seizure disorders in autism; 
studies to define the neurobiological basis of neurological abnormalities and 
neuropsychiatric symptoms, including motor stereotypies, gait abnormalities, 
akinesias, dyskinesias, obsessive/compulsive traits, and the exacerbation of these 
symptoms, including the role of neuroimmune/autoimmune factors; studies that seek 
to define basic processing deficits using neuropsychological and cognitive 
neuroscience techniques; studies to develop animal models of brain dysfunction in 
autism and autism spectrum disorders, based on either genetic or environmental 
factors or their interaction.

o  Cognitive Science:  Developmental studies of relevant behaviors during infancy 
including attention to social and nonsocial stimuli, affective behavior, gaze, 
vocalization, imitation, initiative, reciprocity, attachment, play, compliance, and 
self-recognition and their emergence in children with autism and autistic spectrum 
disorders; research on the delays and deviations in social behavior and cognition 
during preschool and middle school, including empathy, receptive social cognitive 
deficits (i.e., difficulties understanding others), and expressive difficulties; 
studies leading to more sophisticated tests of higher cognitive functioning, 
especially in social, communicative, reasoning, and problem-solving areas, as well 
as tests of basic attentional, emotional and cognitive deficits that may underlie 
these deficits or be precursors to them; studies of theory of mind, of 
unconventional verbal behaviors, and of the sensory-motor factors involved in 
relevant social cognition; and the development, validation, and refinement of 
interventions designed to address deficits in complex social and cognitive 
abilities or their developmental precursors; interventions designed to lessen or 
remediate cognitive deficits.

o  Communication Skills:  Longitudinal, developmental studies of behaviors that are 
precursors to later communication and their emergence in children with autism and 
autistic spectrum disorders; sensory, motor, and social-cognitive impairments that 
impact upon interaction and communication; predictors of loss of or regression in 
expressive language abilities; interventions designed to remediate communication 
and related deficits across the life-span.

o  Pharmacological/Biological Interventions:  Studies aimed at developing and 
testing the efficacy and safety of pharmacological agents that specifically target 
the core features of autism and autistic spectrum disorders; studies of the 
efficacy and safety of pharmacological and combined treatments for the most common 
and impairing psychopathology associated with autism (e.g., hyperactivity, 
impulsivity, aggression, self-injury, and obsessive-compulsive symptoms); studies 
that relate characteristics of individuals (or diagnostic subtypes) to therapeutic 
response and treatment outcomes (also see “Pharmacogenomics”, below);  new 
approaches to treatment that build on advances in neuroscience, genetics, 
immunology, and other neurobiologic fields; focused interventions that test 
specific theories or hypotheses regarding possible neuropathogenesis; studies that 
address the benefits of combined drug and cognitive, behavioral, or psychosocial 
interventions; development of innovative methodologies and outcome measures.

o  Pharmacogenomic Studies:  construction and analysis of SNP haplotypes that 
predict therapeutic response or adverse reactions to drugs; correlation of drug 
response profiles with intermediate phenotypes (e.g., brain imaging, 
neurophysiology, learning and memory, sustained attention); identification of 
biomarkers to resolve clinical heterogeneity and heterogeneity of therapeutic drug 
response;  application of high-throughput approaches to screen for drug candidates 
metabolized by or inhibitors of polymorphic drug-metabolizing enzymes, e.g., 
CYP2D6; studies of genetically determined functional changes in nuclear and cell 
surface receptors to explain the ineffectiveness of therapeutic agents and adverse 
or paradoxical drug responses; studies of allelic variation occurring in individual 
transporter genes that are associated with a functional consequence.

o  Psychosocial Interventions:  Studies developing new treatments (e.g., 
behavioral, cognitive-behavioral) and studies validating, refining, and comparing 
approaches to the treatment of persons with autism and autism spectrum disorders 
and their families, as well as studies that analyze and define the critical 
features of effective intervention; studies that relate characteristics of 
individuals (or diagnostic subtypes) to treatment outcomes; research on relevant 
contextual factors including physical and community environments, parent-child and 
sibling-child relationship factors, and peer-child interactions; studies addressing 
generalization or the transfer of learning from one setting to another; studies 
that develop and test interventions for infants and toddlers with confirmed or 
suspected autism spectrum disorders; studies that develop and test interventions to 
outcome in school and community settings throughout the lifespan; development of 
innovative methodologies and outcome measures.

o  Services Research:  research on the organization, delivery, coordination, and 
financing of services for persons with autism spectrum disorders, and their 
families, within or across service settings; studies aimed at better identifying 
and addressing changes in service and rehabilitative needs across the life-span, 
including during transitions from childhood to adolescence, and adolescence to 
adulthood; interventions to improve the quality and outcomes of treatment and 
rehabilitation services; studies to develop improved measures of adaptive 
capabilities for children, adolescents, and adults with autism spectrum disorders; 
studies of ways to coordinate or integrate services across settings including 
specialty mental health, general health, and other settings such as educational, 
vocational, and housing services, in order to maximize receipt of appropriate 
services; and research on the economic factors effecting the delivery of needed 
services and treatments including cost-benefit, cost-effectiveness, and cost 
utility analyses of service interventions.

MECHANISMS OF SUPPORT

This PA will use the NIH research project grant (R01), small grant (R03), and 
exploratory/developmental grant (R21) award mechanisms.  As an applicant, you will 
be solely responsible for planning, directing, and executing the proposed project.  
Competing supplements to existing studies can also be used.

The Small Grant (R03) provides 2 years of funding with a maximum of $50,000 direct 
costs for each year.  Instructions for the R03 application can be found at 
(http://grants.nih.gov/grants/guide/pa-files/PA-03-108.html).  Applicants 
considering use of this mechanism for an application to NINDS should contact NINDS 
staff (below) for information about specific restrictions.

The Exploratory/Developmental Grant (R21) provides 2 years of funding with a 
maximum of $275,000 direct costs over the entire budget period; with no 1 year 
exceeding $200,000.  Instructions for the R21 application may be found at:  
http://grants.nih.gov/grants/guide/pa-files/PA-03-107.html.  Applicants considering 
use of this mechanism for an application to NINDS should contact NINDS staff 
(below) for information about specific restrictions.

This PA uses just-in-time concepts.  It also uses the modular budgeting as well as 
the non-modular budgeting formats (see 
http://grants.nih.gov/grants/funding/modular/modular.htm).  Specifically, if you 
are submitting an application with direct costs in each year of $250,000 or less, 
use the modular budget format.  Otherwise follow the instructions for non-modular 
budget research grant applications.  This program does not require cost sharing as 
defined in the current NIH Grants Policy Statement at 
http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.htm

Investigators might also want to consider relevant Institute-specific mechanisms, 
including the NIMH collaborative R01 mechanism “Collaborative R01s for Clinical and 
Services Studies of Mental Disorders and Aids,” PA-01-123, which is located at 
http://grants.nih.gov/grants/guide/pa-files/PA-01-123.html; the NIMH R34 mechanism 
for exploratory interventions and services research grants “From Intervention 
Development to Services:  Exploratory Research Grants”, PAR-03-078, which is 
located at http://grants.nih.gov/grants/guide/pa-files/PAR-03-078.html and the NIH 
R34 mechanism, which is available at 
http://grants.nih.gov/grants/guide/pa-files/PA-04-008.html.

ELIGIBLE INSTITUTIONS

You may submit (an) application(s) if your institution has any of the following 
characteristics

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

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to carry out the 
proposed research is invited to work with their institution to develop an 
application for support.  Individuals from underrepresented racial and ethnic 
groups as well as individuals with disabilities are always encouraged to apply for 
NIH programs.

SPECIAL REQUIREMENTS

Dissemination of Data, Biomaterials for Genetic Studies

Applications for genetic studies must include a data sharing plan.  Data and 
biomaterials from subjects included in genetic projects funded under this PA will 
be made available and distributed to the broader scientific community, in 
accordance with existing procedures and protocols for the NIMH Human Genetics 
Initiative.  Pharmacogenomic studies are expected to make data available for 
inclusion in PharmGKB (http://www.pharmgkb.org), an NIH-supported knowledge base 
for pharmacogenetic information (see below).  It is expected that the information 
to be shared includes all genetic, clinical and diagnostic information, in addition 
to cell lines and DNA.  It is preferable that data and materials generated in 
genetics projects funded under this PA should be placed in common, public cell 
repositories and databases that are widely accessible by investigators in the 
scientific community.  An NIMH-supported data management facility and cell 
repository - the NIMH Center for Collaborative Genetic Studies on Mental Disorders 
(http://nimhgenetics.org) - is such a community resource.  Further information is 
available from the NIMH program staff contact listed below.

It is expected that the investigator’s data sharing plan will specify the following 
elements:  (1) the creation of comprehensive and verified databases that contain 
all clinical, diagnostic, and genetic information collected and produced in the 
project; (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 biomaterials (DNA samples, cell 
lines) are widely distributed to qualified investigators in the scientific 
community; (4) a protocol for wide dissemination of these data and biomaterials; 
(5) a timetable for distribution; and (6) an assurance that data and biomaterials 
are disseminated in a manner comparable to pre-existing protocols and procedures 
for distributing such data and biomaterials in the NIMH Human Genetics Initiative 
(see http://zork.wustl.edu/nimh/NIMH_initiative/NIMH_initiative_link.html).

NIMH, in consultation with NIH’s Office of the General Counsel, the National Human 
Genome Research Institute's Ethical, Legal, and Social Implications Research 
Program and the Department of Health and Human Services' Office for Human Research 
Protections, has developed a model consent form for use in human genetic research 
at http://zork.wustl.edu/nimh/NIMH_initiative/NIMH_initiative_link.html.  Consent 
forms for pharmacogenomic studies should also include explicit disclosure that de-
identified data will be posted to PharmGKB.

WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this PA and welcome the opportunity to 
answer questions from potential applicants.  Inquiries may fall into two areas:  
scientific/research and financial or grants management issues:

o  Direct your questions about scientific/research issues to:

Ann Wagner, Ph.D.
National Institute of Mental Health
6100 Executive Boulevard, Room 7149, MSC 9633
Bethesda, MD  20857-9633
Telephone:  (301) 443-4283
FAX:  (301) 443-4045
Email:  awagner@mail.nih.gov

Judith Cooper, Ph.D.
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
Email:  cooperj@nidcd.nih.gov

Alice Kau, Ph.D.
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 4B09F, MSC 7510 
Bethesda, MD  20892-7510
Telephone:  (301) 496-1383
FAX:  (301) 496-3791
Email:  kaua@mail.nih.gov

Deborah Hirtz, M.D.
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard, Room 2212, MSC 9250
Bethesda, MD  20892-9250
Telephone:  (301) 496-5821
FAX:  (301) 480-1080
Email:  dh83f@nih.gov

Cindy P. Lawler, Ph.D.
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

Kathy Mann Koepke, Ph.D.
National Institute of Nursing Research
6701 Democracy Boulevard, Suite 7101, MSC 4870
Bethesda, MD  20892-4870
Telephone:  (301496-9623
FAX:  (301) 480-8260
Email:  koepkek@mail.nih.gov

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

Rebecca Claycamp, CRA
Chief Grants Management Officer
National Institute of Mental Health
6001 Executive Boulevard, Room 6122, MSC 9605
Bethesda, MD  20892-9605
Telephone:  (301) 443-2811
FAX:  (301) 443-6885
Email:  rc253d@nih.gov

Christopher Robey
Grants Management Team Leader
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17K - MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 435-6996
FAX:  (301) 480-4783
Email:  robeyj@mail.nih.gov

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

Rita V. Sisco
Grants Management Branch
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard, Room 3265, MSC 9537
Rockville, MD  20852-9537
Telephone:  (301) 496-7488
FAX:  (301) 402-0219
Email:  siscor@ninds.nih.gov

Lerlita Garcia
Grants Management Branch
National Institute of Environmental Health Sciences
P.O. Box 12233, MD EC-22
Research Triangle Park, NC  27709
Telephone:  (919) 316-4638
FAX:  (919) 541-2860
Email:  garcial@niehs.nih.gov

Diane E. Drew
Office of Grants and Contracts Management
National Institute of Nursing Research
6701 Democracy Boulevard, Suite 7101, MSC 4870
Bethesda, MD  20892-4870
Telephone:  (301) 594-2807
FAX:  (301) 451-5651
Email:  diane_drew@nih.gov

SUBMITTING AN APPLICATION

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

The title and number of this program announcement must be typed on line 2 of the 
face page of the application form and the YES box must be checked.

APPLICATION RECEIPT DATES:  Applications submitted in response to this program 
announcement will be accepted at the standard application deadlines, which are 
available at http://grants.nih.gov/grants/dates.htm.  Application deadlines are 
also indicated in the PHS 398 application kit.

SPECIFIC INSTRUCTIONS FOR MODULAR BUDGET GRANT APPLICATIONS:  Applications 
requesting up to $250,000 per year in direct costs must be submitted in a modular 
budget grant format.  The modular budget grant format simplifies the preparation of 
the budget in these applications by limiting the level of budgetary detail.  
Applicants request direct costs in $25,000 modules.  Section C of the research 
grant application instructions for the PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step 
guidance for preparing modular grants.  Additional information on modular grants is 
available at http://grants.nih.gov/grants/funding/modular/modular.htm.

SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER YEAR:  
Applications requesting $500,000 or more in direct costs for any year must include 
a cover letter identifying the NIH staff member within one of NIH institutes or 
centers who has agreed to accept assignment of the application.

Applicants requesting more than $500,000 must carry out the following steps:

1) Contact the IC program staff at least 6 weeks before submitting the application, 
i.e., as you are developing plans for the study; 

2) Obtain agreement from the IC staff that the IC will accept your application for 
consideration for award; and,

3) Identify, in a cover letter sent with the application, the staff member and IC 
who agreed to accept assignment of the application.

This policy applies to all investigator-initiated new (type 1), competing 
continuation (type 2), competing supplement, or any amended or revised version of 
these grant application types.  Additional information on this policy is available 
in the NIH Guide for Grants and Contracts, October 19, 2001 at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html.

SENDING AN APPLICATION TO THE NIH:  Submit a signed, typewritten original of the 
application, including the checklist, and five signed photocopies in one package 
to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)

APPLICATION PROCESSING:  Applications must be mailed on or before the receipt dates 
described at http://grants.nih.gov/grants/funding/submissionschedule.htm.  The CSR 
will not accept any application in response to this PA that is essentially the same 
as one currently pending initial review unless the applicant withdraws the pending 
application.  The CSR will not accept any application that is essentially the same 
as one already reviewed.  This does not preclude the submission of a substantial 
revision of an unfunded version of an application already reviewed, but such 
application must include an Introduction addressing the previous critique.

Although there is no immediate acknowledgement of the receipt of an application, 
applicants are generally notified of the review and funding assignment within 8 
weeks.

PEER REVIEW PROCESS

Applications submitted for this PA will be assigned on the basis of established PHS 
referral guidelines.  Appropriate scientific review groups convened in accordance 
with the standard NIH peer review procedures (http://www.csr.nih.gov/refrev.htm) 
will evaluate applications for scientific and technical merit.

As part of the initial merit review, all applications will:

o  Undergo a selection process in which only those applications deemed to have the 
highest scientific merit, generally the top half of applications under review, will 
be discussed and assigned a priority score
o  Receive a written critique
o  Receive a second level review by the appropriate national advisory council or 
board

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of biological 
systems, improve the control of disease, and enhance health.  In the written 
comments, reviewers will be asked to evaluate application in order to judge the 
likelihood that the proposed research will have a substantial impact on the pursuit 
of these goals.  The scientific review group will address and consider each of the 
following criteria in assigning the application’s overall score, weighting them as 
appropriate for each application.

o  Significance 
o  Approach 
o  Innovation
o  Investigator
o  Environment

The application does not need to be strong in all categories to be judged likely to 
have major scientific impact and thus deserve a high priority score.  For example, 
an investigator may propose to carry out important work that by its nature is not 
innovative but is essential to move a field forward.

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?

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?

INNOVATION:  Does the project employ novel concepts, approaches or methods? Are the 
aims original and innovative? Does the project challenge existing paradigms or 
develop new methodologies or technologies?

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

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?  

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK:  The involvement of human subjects 
and protections from research risk relating to their participation in the proposed 
research will be assessed. (See criteria included in the section on Federal 
Citations, below).http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm

INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH:  The adequacy of plans to 
include subjects from both genders, all racial and ethnic groups (and subgroups), 
and children as appropriate for the scientific goals of the research will be 
assessed.  Plans for the recruitment and retention of subjects will also be 
evaluated. (See Inclusion Criteria in the sections on Federal Citations, below).

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH:  If vertebrate animals are to be 
used in the project, the five items described under Section f of the PHS 398 
research grant application instructions (rev. 5/2001) will be assessed.

ADDITIONAL REVIEW CONSIDERATIONS

SHARING RESEARCH DATA:  Applicants requesting more than $500,000 in direct costs in 
any year of the proposed research are expected to include a data sharing plan in 
their application.  The reasonableness of the data sharing plan or the rationale 
for not sharing research data will be assessed by the reviewers.  However, 
reviewers will not factor the proposed data sharing plan into the determination of 
scientific merit or priority score http://grants.nih.gov/grants/policy/data_sharing 

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

AWARD CRITERIA

Applications submitted in response to a PA will compete for available funds with 
all other recommended applications.  The following will be considered in making 
funding decisions:

o  Scientific merit of the proposed project as determined by peer review
o  Availability of funds
o  Relevance to program priorities

REQUIRED FEDERAL CITATIONS 

HUMAN SUBJECTS PROTECTION:  Federal regulations (45CFR46) require that applications 
and proposals involving human subjects must be evaluated with reference to the 
risks to the subjects, the adequacy of protection against these risks, the 
potential benefits of the research to the subjects and others, and the importance 
of the knowledge gained or to be gained. 
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm

DATA AND SAFETY MONITORING PLAN:  Data and safety monitoring is required for all 
types of clinical trials, including physiologic, toxicity, and dose-finding studies 
(phase I); efficacy studies (phase II), efficacy, effectiveness and comparative 
trials (phase III).  The establishment of data and safety monitoring boards (DSMBs) 
is required for multi-site clinical trials involving interventions that entail 
potential risk to the participants.  (NIH Policy for Data and Safety Monitoring, 
NIH Guide for Grants and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

SHARING RESEARCH DATA:  Starting with the October 1, 2003 receipt date, 
investigators submitting an NIH application seeking $500,000 or more in direct 
costs in any single year are expected to include a plan for data sharing or state 
why this is not possible http://grants.nih.gov/grants/policy/data_sharing.  
Investigators should seek guidance from their institutions, on issues related to 
institutional policies, local IRB rules, as well as local, state and Federal laws 
and regulations, including the Privacy Rule.  Reviewers will consider the data 
sharing plan but will not factor the plan into the determination of the scientific 
merit or the priority score.

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

All investigators proposing clinical research should read the "NIH Guidelines for 
Inclusion of Women and Minorities as Subjects in Clinical Research - Amended, 
October, 2001," published in the NIH Guide for Grants and Contracts on October 9, 
2001
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a 
complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.  The 
amended policy incorporates:  the use of an NIH definition of clinical research; 
updated racial and ethnic categories in compliance with the new OMB standards; 
clarification of language governing NIH-defined Phase III clinical trials 
consistent with the new PHS Form 398; and updated roles and responsibilities of NIH 
staff and the extramural community.  The policy continues to require for all NIH-
defined Phase III clinical trials that:  a) all applications or proposals and/or 
protocols must provide a description of plans to conduct analyses, as appropriate, 
to address differences by sex/gender and/or racial/ethnic groups, including 
subgroups if applicable; and b) investigators must report annual accrual and 
progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic 
group differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS:  The 
NIH maintains a policy that children (i.e., individuals under the age of 21) must 
be included in all human subjects research, conducted or supported by the NIH, 
unless there are scientific and ethical reasons not to include them.  This policy 
applies to all initial (Type 1) applications submitted for receipt dates after 
October 1, 1998.

All investigators proposing research involving human subjects should read the "NIH 
Policy and Guidelines" on the inclusion of children as participants in research 
involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm.

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS:  NIH policy 
requires education on the protection of human subject participants for all 
investigators submitting NIH proposals for research involving human subjects.  You 
will find this policy announcement in the NIH Guide for Grants and Contracts 
Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

HUMAN EMBRYONIC STEM CELLS (hESC):  Criteria for federal funding of research on 
hESCs can be found at http://stemcells.nih.gov/index.asp and at  
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  Only research 
using hESC lines that are registered in the NIH Human Embryonic Stem 
Cell Registry will be eligible for Federal funding (see http://escr.nih.gov).  It 
is the responsibility of the applicant to provide, in the project description and 
elsewhere in the application as appropriate, the official NIH identifier(s)for the 
hESC line(s)to be used in the proposed research.  Applications that do not provide 
this information will be returned without review.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT:  The Office 
of Management and Budget (OMB) Circular A-110 has been revised to provide public 
access to research data through the Freedom of Information Act (FOIA) under some 
circumstances.  Data that are (1) first produced in a project that is supported in 
whole or in part with Federal funds and (2) cited publicly and officially by a 
Federal agency in support of an action that has the force and effect of law (i.e., 
a regulation) may be accessed through FOIA.  It is important for applicants to 
understand the basic scope of this amendment.  NIH has provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this 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.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:  The 
Department of Health and Human Services (DHHS) issued final modification to the 
“Standards for Privacy of Individually Identifiable Health Information”, the 
“Privacy Rule,” on August 14, 2002.  The Privacy Rule is a federal regulation under 
the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that 
governs the protection of individually identifiable health information, and is 
administered and enforced by the DHHS Office for Civil Rights (OCR).  Those who 
must comply with the Privacy Rule (classified under the Rule as “covered entities”) 
must do so by April 14, 2003  (with the exception of small health plans which have 
an extra year to comply).

Decisions about applicability and implementation of the Privacy Rule reside with 
the researcher and his/her institution.  The OCR website (http://www.hhs.gov/ocr/) 
provides information on the Privacy Rule, including a complete Regulation Text and 
a set of decision tools on “Am I a covered entity?”  Information on the impact of 
the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress 
monitoring of grants, cooperative agreements, and research contracts can be found 
at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES:  All applications and proposals for 
NIH funding must be self-contained within specified page limitations.  Unless 
otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be 
used to provide information necessary to the review because reviewers are under no 
obligation to view the Internet sites.  Furthermore, we caution reviewers that 
their anonymity may be compromised when they directly access an Internet site.

HEALTHY PEOPLE 2010:  The Public Health Service (PHS) is committed to achieving the 
health promotion and disease prevention objectives of "Healthy People 2010," a PHS-
led national activity for setting priority areas.  This PA is related to one or 
more of the priority areas.  Potential applicants may obtain a copy of "Healthy 
People 2010" at http://www.healthypeople.gov/.

AUTHORITY AND REGULATIONS:  This program is described in the Catalog of Federal 
Domestic Assistance at http://www.cfda.gov/ and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health Systems 
Agency review.  Awards are made under the authorization of Sections 301 and 405 of 
the Public Health Service Act as amended (42 USC 241 and 284 and under Federal 
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.  All awards are subject to the 
terms and conditions, cost principles, and other considerations described in the 
NIH Grants Policy Statement.  The NIH Grants Policy Statement can be found at 
http://grants.nih.gov/grants/policy/policy.htm 

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


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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