Expired PA-13-216: Research on Autism Spectrum Disorders (R01)

Part 1. Overview Information

Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Mental Health (NIMH) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) National Institute on Deafness and Other Communication Disorders (NIDCD) National Institute of Environmental Health Sciences (NIEHS) National Institute of Neurological Disorders and Stroke (NINDS) Office of Dietary Supplements (ODS)
Funding Opportunity Title	Research on Autism Spectrum Disorders (R01)
Activity Code	R01 Research Project Grant
Announcement Type	Reissue of PA-10-158
Related Notices	August 5, 2016 - This PA has been reissued as PA-16-388. May 2, 2016 - Notice to Extend PA-13-216. See Notice NOT-MH-16-009. NOT-OD-16-004 - NIH & AHRQ Announce Upcoming Changes to Policies, Instructions and Forms for 2016 Grant Applications (November 18, 2015) NOT-OD-16-006 - Simplification of the Vertebrate Animals Section of NIH Grant Applications and Contract Proposals (November 18, 2015) NOT-OD-16-011 - Implementing Rigor and Transparency in NIH & AHRQ Research Grant Applications (November 18, 2015) June 4, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same. August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications. May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.
Funding Opportunity Announcement (FOA) Number	PA-13-216
Companion Funding Opportunity	PA-13-217, R21 Exploratory/Developmental Grant PA-13-218, R03 Small Grant Program
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.242, 93.865, 93.173, 93.113, 93.853
Funding Opportunity Purpose	This Funding Opportunity Announcement (FOA) encourages research grant applications to support research designed to elucidate the etiology, epidemiology, diagnosis, treatment, and optimal means of service delivery in relation to autism spectrum disorders (ASD). Basic, clinical, and applied studies are encouraged.

Key Dates

Posted Date	May 1, 2013
Open Date (Earliest Submission Date)	May 5, 2013
Letter of Intent Due Date(s)	Not Applicable
Application Due Date(s)	Standard dates apply, by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	Standard dates apply
Advisory Council Review	Standard dates apply
Earliest Start Date	Standard dates apply
Expiration Date	New Date August 5, 2016 per issuance of PA-16-388. (Original Expiration Date: September 8, 2016)
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to encourage research grant applications to support research designed to elucidate the etiology, epidemiology, diagnosis, treatment, and optimal means of service delivery in relation to autism spectrum disorders (ASD).

The Interagency Autism Coordinating Committee (IACC) is an advisory committee to the federal government that develops and annually updates a strategic plan for the conduct and support of ASD research. This FOA is intended to support the broad research goals of the IACC Strategic Plan for ASD Research.

Research Objectives

Autism Spectrum Disorders share a cluster of impairments in reciprocal social interaction, communication, and the presence of stereotyped behavior, interests, or activities. These complex disorders are usually of lifelong duration and affect multiple aspects of development, learning, and adaptation at home, in school, and in the community, thus representing a pressing public health need. The etiologies of these disorders are not yet understood, but may include a combination of genetic, metabolic, immunologic, infectious or other environmental influences.

Clinical research involving ASD 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 ASD, 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 new treatment and interventions, specifically those that hypothesize and test a mechanism of treatment effect, as well as the development of validated instruments that may be used as outcome measures in treatment and intervention studies.

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

Epidemiology: Studies of the genetic and environmental epidemiology of ASD to determine risk and protective processes in the etiology of the disorder, including environmental exposures during pregnancy and early childhood; longitudinal studies of high-risk populations; epidemiologic research on interactive genetic and environmental factors or processes that increase or decrease risk for ASD; studies of the developmental course of ASD 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.

Screening, Early Identification, and Diagnosis: Studies of key diagnostic and phenotypic features of ASD associated with various stages of development, including those focused on adults; development of new screening tools for use in a variety of settings; assessment of comorbid features including attentional or executive dysfunctions, and epilepsy; the creation of new measures to be used in longitudinal and/or treatment studies, and measures that further differentiate subtypes of ASD.

Genetic Studies: Family-based or population-based genetic analyses that aim to: identify specific susceptibility genes using whole genome/exome approaches; investigate epigenetic mechanisms and long range control of gene expression; systems approaches that incorporate multiple types of -omics data; detect locus heterogeneity; and analyze the interaction of autism susceptibility genes with environmental exposures and/or genes responsive to environmental insult. An area of particular interest is the effect of genetic factors on therapeutic drug response in individuals with ASD (see Pharmacogenomic Studies, below).

Brain Mechanisms: Studies of brain mechanisms underlying the development, regulation, and modulation of behaviors characterizing ASD, particularly those mechanisms involving communication and social interaction; studies of brain mechanisms and biological factors underlying 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 ASD; studies to define the neurobiological basis of neurological abnormalities and neuropsychiatric symptoms 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 using model systems to examine brain dysfunction related to ASD, based on either genetic or environmental factors or their interaction; studies using novel reagents and tools to identify molecular, cellular, or developmental mechanisms distinguishing ASD and control subjects.

Shared Neurobiology of Autism with Fragile X, Rett Syndrome, and Related Disorders: Studies of developmental and functional processes, pathways, and brain mechanisms that will lead to an understanding of shared etiology or pathophysiology among these disorders; analysis of autism-related neurobiological and behavioral phenotypes in related single gene disorders; studies that focus on basic research and/or preclinical testing in model systems to develop and assess the safety and biological activity of novel therapeutic compounds that could be used to treat autism and related disorders; analyses that would identify useful and specific clinical endpoints that would register measurable improvements in response to treatment interventions in clinical populations as well as studies that would facilitate future development of clinical trials in these populations.

Cognitive Science: Developmental studies of relevant behaviors during infancy including attention to social and nonsocial stimuli, affective behavior, gaze, imitation, reciprocity and play, and their emergence in infants and children with ASD; research on social behavior and cognition across the life-span, including receptive social cognitive deficits (i.e., difficulties understanding others), and expressive difficulties; studies leading to more sophisticated measures of higher cognitive functioning, especially in social, communicative and problem-solving areas; studies of sensory-motor factors and multisensory integration.

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

Pharmacological/Biological Interventions: Studies testing new pharmacological agents that specifically target the core social deficits of ASD; studies that relate characteristics of individuals to therapeutic response and treatment outcomes (also see Pharmacogenomic Studies, below); new approaches to treatment that build on advances in neuroscience, genetics, immunology, and other neurobiologic fields; identification and validation of novel treatment targets and molecular screening approaches or biomarkers that assess effects on key biological, neurodevelopmental and/or behavioral endpoints disrupted in ASD; focused interventions that test specific theories or hypotheses regarding possible neuropathogenesis; and development of validated outcome measures.

Pharmacogenomic Studies: Analysis of SNP and DNA sequence data that: predict therapeutic response or adverse reactions to drugs; correlate drug response profiles with intermediate phenotypes (e.g., brain imaging, neurophysiology, learning and memory); identify biomarkers to resolve clinical heterogeneity and heterogeneity of therapeutic drug response; apply 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; and studies of allelic variation occurring in individual transporter genes that are associated with a functional consequence.

Psychosocial/Behavioral Interventions: Studies to develop new interventions for persons with ASD, as well as studies that analyze and define the critical features of effective intervention; studies that relate characteristics of individuals to treatment outcomes; the development, validation, and refinement of interventions designed to address deficits in complex social and cognitive abilities or their developmental precursors; studies that develop and test interventions for infants and toddlers who are at-risk for ASD; studies that develop and test interventions to improve outcomes in school and/or community settings; and development of validated outcome measures.

Services Research: Research on the organization, delivery, coordination, and financing of services for persons with ASD 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 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 assessing the value and improving the efficiency of the delivery of needed services and treatments.

Section II. Award Information

Funding Instrument	Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
Application Types Allowed	New Renewal Resubmission Revision The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Award Budget	Application budgets are not limited, but need to reflect the actual needs of the proposed project.
Award Project Period	The total project period may not exceed 5 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

Public/State Controlled Institutions of Higher Education
Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

Hispanic-serving Institutions
Historically Black Colleges and Universities (HBCUs)
Tribally Controlled Colleges and Universities (TCCUs)
Alaska Native and Native Hawaiian Serving Institutions
Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

Small Businesses
For-Profit Organizations (Other than Small Businesses)

Governments

State Governments
County Governments
City or Township Governments
Special District Governments
Indian/Native American Tribal Governments (Federally Recognized)
Indian/Native American Tribal Governments (Other than Federally Recognized)
Eligible Agencies of the Federal Government
U.S. Territory or Possession

Other

Independent School Districts
Public Housing Authorities/Indian Housing Authorities
Native American Tribal Organizations (other than Federally recognized tribal governments)
Faith-based or Community-based Organizations
Regional Organizations
Non-domestic (non-U.S.) Entities (Foreign Institutions)

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization 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 support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
Of an application with a changed grant activity code.

Section IV. Application and Submission Information

1. Requesting an Application Package

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Required and Optional Components

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

SF424(R&R) Cover