Office Enterprise 2007 RFA-MH-09-170 Recovery Act

Part I Overview Details

Department of Well being and Human Providers

Collaborating Organizations
Nationwide Institutes of Wellness (NIH), (

Components of Taking part Organizations
National Institute of Mental Wellness (NIMH), (
Nationwide Institute of Youngster Well being and Human Advancement (NICHD), (
National Institute on Deafness as well as other Communication Ailments (NIDCD), (
National Institute of Environmental Health Sciences (NIEHS),(
Countrywide Institute of Neurological Ailments and Stroke (NINDS),(

Title:  Recovery Act Constrained Competition:  Research to handle the Heterogeneity in Autism Spectrum Problems (R01)

Announcement Type

New


Request for Purposes (RFA) Number: RFA-MH-09-170

NOTICE: Applications submitted in response to this Funding Possibility Announcement (FOA) for Federal help has to be submitted electronically by way of Grants.gov ( making use of the SF424 Investigation and Relevant (R&R) forms and the SF424 (R&R) Application Guide.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA have to be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least four (4) weeks prior to the grant submission date. See Section IV.

Catalog of Federal Domestic Support Quantity(s)
93.701

Key Dates
Release/Posted Date: March 23, 2009
Opening Date: April 12, 2009 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): April 12, 2009
NOTE: On-time submission requires that purposes be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization). 
Application Due Date(s):  May 12, 2009
AIDS Application Due Date(s): Optional. Add Information Here
Peer Review Date(s): July 2009
Council Review Date(s): August 2009
Earliest Anticipated Start Date(s): September 30, 2009
Additional Data To Be Available Date (Activation Date): Not Applicable
Expiration Date: May 13, 2009


Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary
Purpose. This NIH Funding Chance Announcement (FOA), supported by funds provided to the NIH under the American Recovery & Reinvestment Act of 2009 (“Recovery Act” or “ARRA”), Public Law 111-5, solicits purposes for the following topic areas relevant to analysis on the heterogeneity of Autism Spectrum Disorders (ASD): Measurement improvement, Biomarkers/biological signatures, Immune and central nervous systems interactions, Genetics/genomics, Environmental Risk Factors, Model growth, Treatment and intervention, and Services study. This FOA provides support for the R01 grant mechanism which supports larger scale studies for which preliminary data exists and proof-of-principle has been established. Mechanism of Support. This FOA will utilize the NIH Research Project (R01) award mechanism and runs in parallel with the following FOAs of essentially identical scientific scope: 1) RFA-MH-09-171, which solicits apps under the NIH Collaborative Investigation Grant (R01) award mechanism; 2) RFA-MH-09-172, which solicits applications under the NIH Exploratory/Developmental Analysis Grant (R21) award mechanism; and 3) RFA-MH-09-173, which solicits purposes under the NIH Clinical Exploratory/Developmental Investigation Grant (R34/Collaborative R34) award mechanism. The R21 mechanism would be used for projects that propose study in the exploratory or preliminary phases. The R34 mechanism would be used for early phases of treatment growth. Funds Available and Anticipated Range of Awards. The NIH intends to commit approximately $57,000,000 to fund between 40-50 grants in response to this FOA and the companion announcements. Budget and Project Period. The total project period for an application submitted in response to this R01 FOA may not exceed two years. Applicants for an R01 award are not constrained in dollars but need to reflect the actual needs of the proposed project. Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply. Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/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. Amount of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs) may be designated on the application. Number of Apps. Applicants may submit more than one application, provided each application is scientifically distinct. Resubmissions.  Resubmission apps are not permitted in response to this FOA. Renewals. Renewal applications are not permitted in response to this FOA. Special Date(s). This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates. Application Materials. See Section IV for application materials. General Info. For general info on SF424 (R&R) Application and Electronic Submission, see these Web sites: SF424 (R&R) Application and Electronic Submission Info: General information on Electronic Submission of Grant Apps: Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY:  (301) 451-5936
Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Chance Description

Section II. Award Data

Section III. Eligibility Details

Section IV. Application and Submission Details

Section V. Application Review Info


Section VI. Award Administration Info


Section VII. Agency Contacts

Section VIII. Other Info - Required Federal Citations


Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Analysis Objectives

Purpose

Autism Spectrum Disorders (ASD) are neurodevelopmental disorders characterized by differences in three core domains of functioning: social behavior, communication abilities, and restricted, repetitive or stereotyped patterns of behavior.  Although these core features exist at varying degrees among all individuals with ASD, considerable heterogeneity exists within this population, which suggests there may be multiple causal factors as well as multiple developmental trajectories for these individuals.  Indeed, a clear barrier to understanding the causes of ASD has been the heterogeneity within this spectrum of problems.  In addition, greater knowledge of the range of ASD phenotypes may lead to more precise diagnostic and screening instruments and will increase the potential for more targeted treatment and intervention strategies. 

Approaches to the study of ASD have evolved over time, as more is learned about these problems.  As with many neurodevelopmental problems, brain dysfunction may precede behavioral abnormalities by months or years, however without identified biomarkers for detection of those with, or at risk, for an ASD, diagnostic methods need to rely on behavioral observations which often occur after the onset of symptoms.  As a result, intervention efforts may miss a critical window of chance to alter the developmental trajectory for these individuals.

Differences in policies, resources and organization across geographic regions result in marked disparities in the types of companies and supports available, as well as in the associated financial costs to individuals and families.  Very little is known about how differences in policy and infrastructure are connected to the variations in access to services and care received, and in turn, how these variations affect outcomes for individuals living with an ASD. 

Most individuals with an ASD will continue to experience difficulties across their lifetime. However symptoms often change in form and severity over time.  Although considerable research has been conducted on the earliest phases of ASD, less is known about adolescence, adulthood, and late life stages, or about the transitions between these stages.  Little research has been carried out to determine prognostic factors or how adults with an ASD currently function or are best supported. 

In response to the urgent public wellbeing significance of ASD, Congress passed the Combating Autism Act (CAA) of 2006.  By way of this Act, Congress intended to accelerate the pace, and improve coordination of scientific discovery in ASD investigation.  The CAA required the advancement of a Strategic Plan for ASD Research ( which was created with the input of the scientific community, as well as advocates and advocacy organizations, including parents, providers, and individuals with ASD.  The plan consists of short and long term analysis objectives across a range of topics, including those relevant to the heterogeneity of ASD, such as the gap areas discussed above. 

To tackle these as well as other gap areas of knowledge on ASD, and to ensure appropriate attention is given to the most critical short-term objectives within the Strategic Plan, applications for investigation projects are being solicited within the following topic areas:

Measurement Development

The diagnosis of an ASD can be reliably made by three years of age, however many children with an ASD demonstrate signs of atypical growth prior to two years of age, and several recent studies have indicated that some cases of ASD may be detected as early as twelve months of age through the use of simple behavioral tests.  The current validated diagnostic measures for ASD are time-consuming and require a relatively high level of expertise to administer.  There is an emerging call for streamlined diagnostic approaches that are easy to administer and are sensitive to change.  Diagnostic tools with high sensitivity and specificity to support large-scale epidemiologic and risk factor studies are also needed.  In addition, while specialized screening tools to identify young children who may be at risk for an ASD have been developed that require further testing and refinement for evidence of efficacy, there is a need for screening instruments which can be used outside of specialty clinics, as well as a need for tools that can screen for “at risk” status in older children, adolescents and adults. 

Examples of relevant study of interest include but are not restricted to the following:
Studies attempting to develop brief, easily administered diagnostic tools for use in large-scale investigations Studies attempting to validate efficient and sensitive diagnostic tools in diverse populations, including underrepresented racial and ethnic groups, and older age groups Study to develop measures that are sensitive to incremental changes in both core and associated symptoms of ASD Studies attempting to improve the sensitivity and specificity of screening instruments for use in community settings (i.e., in the general population) Analysis to validate screening tools in diverse populations
Biomarkers/Biological Signatures

Currently, the diagnosis of an ASD or the detection of risk for an ASD is based on behavioral and cognitive signs which may reflect atypical brain improvement.  However, brain along with other biological differences are likely to be present prior to the observable signs.  Biomarkers for ASD can potentially identify individuals with the disorder, or those at risk for developing ASD, before the emergence of behavioral manifestations and the altered developmental trajectories are established, although determining such biomarkers has been complicated by the heterogeneity of the disorder.  Differences in brain structure, and/or functional brain activity patterns can serve as biomarkers, as can hormones, neurotransmitters, receptors, etc.  The identification and validation of robust candidate biomarkers predictive of ASD risk, course, prognosis, and treatment response, will be imperative to understanding and treating ASD.   In all cases, the biomarker should be effective on an individual basis, rather than from pooled individuals. Also, biomarkers appropriate for this funding opportunity announcement may be intended to be used with behavioral measures, but behavioral measures alone are not considered biomarkers here. In addition, an integrated panel of clinically relevant biomarkers (e.g., genes, proteins, brain structure and function) and behavioral indicators could serve to create biological signatures for ASD.  Biomarkers could be noninvasively obtained (e.g., making use of optical or magnetic resonance imaging, etc.) or obtained with minimal invasiveness (e.g., employing genetic, protein or metabolic signatures, physiological measures, etc.) Biomarkers developed may be useful across the lifespan or targeted to particular age groups (e.g. infancy, childhood, adolescence, adulthood).  High-throughput biomarker assays are also encouraged. 

Identifying, parameterizing, optimizing and validating the use of particular biomarkers associated with autism, with regard to their relationship to brain or behavioral function, are among the study activities encouraged. 

Examples of relevant research of interest include but are not constrained to the following:
Research to identify predictive biomarkers or biosignatures for trajectory of risk and/or onset Research to identify biomarkers or biosignatures that track the course of ASD symptoms across time Investigation to establish biomarkers or biosignatures for treatment response and adverse effects (e.g., pharmacogenetic markers) Investigation to identify biomarkers or biosignatures associated with clinical phenotypes (e.g., individuals who experience a regression at some point during growth; individuals who appear to have improved significantly in their functioning and symptom expression) or intermediate phenotypes Study focusing on improving or developing technologies for biomarker assay improvement (e.g., high throughput assays, toolkits that enable other researchers to use the biomarker with appropriate hardware, software, or wetware needed to carry out the study, advancement of a novel detection system for measuring a particular biomarker, novel technologies that enable new biomarkers to be identified) Research focusing on developing a reliable method of identifying individuals with ASD and mitochondrial dysfunction
Immune and Central Nervous Systems Interactions

It is well known that there is bi-directional communication between the immune system and the central nervous system (CNS) and that the immune system may modulate the central nervous system differently across the lifespan.   For example, exposure to a neuroimmune challenge early in life can influence brain growth, and evidence suggests that neuroimmune molecules may influence normal growth and synaptic plasticity of the mammalian brain.  Other studies suggest the possibility that the immune system may play a role in the growth of ASD and other neurodevelopmental disorders, e.g. by immune system activation during early growth.  In order to understand possible contributions of immune-neural interactions to ASD, it is critical to identify mechanisms by which interactions between the metabolic and/or immune system and the CNS may contribute to neurodevelopmental processes disrupted in ASD.  Studies making use of relevant cell systems and mammalian and non-mammalian species are appropriate.   Studies spanning multiple levels of analysis (e.g., genes, molecules, cells, circuits, systems, behavior) are appropriate within the constraints of the constrained project period.  

Examples of relevant study of interest include but are not minimal to the following:
Studies characterizing the proximal and long-term consequences of intrauterine and systemic inflammation, including the effects of subclinical maternal illness, on neurobiological functions relevant to ASD Studies examining the effects of early life stress on interactions between the immune system and CNS during pre- and postnatal life and neurobiological functions relevant to ASD Studies characterizing the developmental expression of cytokines, chemokines, receptors, and related signaling molecules in brain regions relevant to ASD Investigation identifying factors regulating brain cytokine and chemokine expression, release, inactivation and degradation during brain improvement, particularly early brain advancement Studies characterizing the effects of changes in blood-brain barrier function and immune molecule infiltration of developing brain on neurodevelopmental processes and neurobiological function relevant to ASD Study examining the effects of auto-antibodies and maternal antibodies on brain advancement Research focusing on the improvement and early validation of models to examine the effects of pre- and early postnatal infection on brain growth and adult brain function and behavior Studies examining combined immune and genetic risk factors in the brain circuitry alterations that have been established as contributing to ASD functional deficits Studies identifying ###### differences in prenatal interactions between the immune system and the CNS that may contribute to the ###### differences in prevalence of ASD Characterize the developmental and/or long-term consequences of metabolic and/or mitochondrial dysfunction on neurobiological functions relevant to ASD 
Genetics/Genomics

Autism Spectrum Issues have a complex genetic etiology and causation is generally thought to involve a complex interplay between genetic factors and non-genetic environmental exposures.  Environmental exposures are thought to mediate gene expression via epigenetic modification at all levels (methylation, histone modification).  Though some progress in identifying genetic susceptibility has been achieved, only a small proportion of the genetic variance is explained and much more study in large cohorts at the level of genomic and epigenomic variation and regulation is needed.  To date, few studies have been focused on potential mechanisms of gene-environment interplay in ASD, and more study to needed to understand how environmental contributors may influence genetic risk. 

Examples of relevant study of interest include but are not constrained to the following:
Analysis conducting methylation-based genetic pathway analysis in ASD Investigation exploring relationships between environmental exposures and epigenetic alterations in ASD Studies examining defects in the epigenome including changes in DNA methylation (global or localized), incorrect histone modification or altered chromatin structure in ASD Studies to determine parent of origin effects on gene expression as potential biomarkers in ASD Analysis focusing on the interaction of the epigenome and the environment in ASD Studies employing systems biology to identify molecular elements, pathways and circuits involved in the molecular pathophysiology of ASD Genome wide studies of epigenomic and genomic variation to identify pathogenic and risk conferring molecular elements in ASD and related phenotypes Examination and functional characterization of candidate genes thought to confer risk for the improvement of ASD Examination and functional characterization of environmentally relevant genes that may confer risk for the improvement of ASD Deep sequencing of candidate genomic regions to unravel the genetic architecture of ASD and associated phenotypes The identification and/or functional characterization of rare nuclear and mitochondrial genetic variants that have a large effect on the ASD phenotype Novel, high-throughput phenotyping and recruitment studies for subjects with ASD and their first degree relatives to augment existing resources in the NIMH Repository Novel approaches in bioinformatics and statistics to integrate and analyze data across all levels of analysis  Novel approaches in bioinformatics and statistics to integrate and analyze data across all levels of analysis, including methods to integrate environmental exposures with genetic and genomic data Studies to develop an understanding of how environmental factors may contribute to structural variation in the genome (e.g. copy range) associated with ASD
Environmental Risk Factors

The role of the environment in ASD etiology is poorly understood, although there is an emerging appreciation that a complete understanding of ASD will involve a contribution of both genetic and environmental risks. The potential impact of environment on autism risk is supported by recent studies reporting associations of specific exposures during critical periods of improvement with autism risk and by a rich body of evidence establishing the ability of environmental exposures to affect a range of childhood cognitive and behavioral outcomes that are relevant to the clinical manifestations of ASD. Several challenges remain, however, for study aimed at linking specific exposures with ASD phenotype, including the genetic and phenotypic heterogeneity of ASD, the broad range of environmental exposures with potential to impact key aspects of brain advancement and limitations in current exposure assessment methodologies. Research is urgently needed to accelerate efforts in this understudied area, as the identification of environmental risk factors provides new opportunities for prevention by means of reduction or elimination of exposures in susceptible populations.  

For the purposes of this FOA, the environment is defined broadly to include, but not be constrained to, pesticides and agrichemicals, air pollution and combustion byproducts, endocrine active chemicals, metals, nutrition, pharmaceuticals and also other medical exposures, infectious agents and psychosocial stressors.

Examples of relevant analysis of interest include, but are not minimal to, the following:
Studies making use of banked maternal, paternal and/or infant biospecimens collected during preconception, pregnancy or early postnatal life that can be linked to clinical outcomes in the offspring for analysis of ASD risk from early exposures. Studies using existing biospecimens from clinically well-characterized individuals with ASD, and appropriate comparison groups, to assess body burden and/or individual sensitivity/susceptibility to specific environmental exposures. Study to determine feasibility of adding new data collection efforts for environmental exposures in existing clinical or population-based studies of ASD. Studies of special populations with known, unique environmental exposures during critical periods of preconception, gestation or early prenatal life that can provide enhanced power for detecting environmental risks for ASD. Studies to determine the feasibility of using existing large scale epidemiologic studies of various wellbeing outcomes to conduct ancillary studies (e.g., nested case control) focused on environmental risk for ASD. Studies employing existing data from a single study, or pooled data from several studies, to conduct new analyses focused on the potential relationship between environmental exposures and specific subtypes of ASD. Studies that link existing environmental monitoring data to existing clinical or population-based studies of ASD to examine the association between individual-level exposures estimates during critical periods of growth and ASD. Interdisciplinary studies to develop and apply approaches that enable bidirectional translation of findings from mechanistic neurotoxicology studies using cellular, molecular and nonhuman models with relevance to ASD to/from ongoing clinical/epidemiologic studies in ASD.
Model Development

Behavioral Model Development

The advancement of animal models is critical to identifying the neurobiological systems most disrupted in ASD,Office Enterprise 2007, following the developmental trajectory that leads to these disruptions, determining the genetic and environmental factors that influence the expression of ASD symptoms, and to testing the efficacy and/or safety of ASD interventions and treatments.  To be useful for these types of studies, animal behavioral models of ASD should replicate one or more of the core behavioral features of ASD.  Projects can include the improvement, standardization, and/or comparison of behavioral measurements in these or other clinically significant domains. Behavioral measurements in both highly controlled and ethologically valid environments are encouraged.  Behavioral assays that capture ASD-relevant ###### differences and/or allow for analysis of ###### as a factor are also strongly encouraged.  Behavioral assays should be appropriate for use with animals from early post-natal life by means of adulthood. 

Behaviors of interest include, but are not constrained to:
Impairments in social behavior, such as reproducible and quantifiable deficits in social perception, emotional recognition, parent-offspring interactions, peer interactions, pair-bonding, and/or self-regulation Impairments in communication, such as reproducible deficits in emitting or appropriately responding to ultrasonic vocalizations, olfactory signals, postural displays, and/or juvenile play Restricted, inflexible, and/or repetitive behaviors, such as motor stereotypies, learning, and/or reversal deficits Other signs/symptoms associated with ASD, such as failure to meet developmental milestones, sleep disturbances, anxiety, aggression, and also other comorbid symptoms Identification of new and/or more specific behavioral phenotypes is also encouraged
Models for Understanding Neurobiological Mechanisms

Experimental models play an important role in promoting a deeper understanding of the molecules and brain systems involved in ASD.  By way of the use of cell systems and intact model systems, multiple levels of analysis can be applied in order to examine the molecular, cellular, and circuits contributing to the phenotypic outcomes of ASD,Microsoft Office 2007 Enterprise, and novel pharmacologic and behavioral interventions can be tested. 

Examples of relevant analysis of interest include but are not limited to the following:
Development and validation of new model systems (cellular and/or animal) that replicate features of ASD and promote the identification of contributing developmental processes and specific molecular targets or neuronal circuits for novel interventions Use of vertebrate and non-vertebrate models to rapidly identify and link gene networks involved in the generation of brain circuitry with behavioral assays relevant to ASD Use of human induced pluripotent stem cells (iPSCs) from neurotypical and ASD populations to identify the fundamental molecular and cellular differences and developmental processes, potential biomarkers, and novel treatment targets for ASD Examination of mechanisms contributing to ###### differences in ASD and/or determination of whether there are specific “parent of origin” contributions to the phenotype Comparison of models of ASD with other models of related neurodevelopmental disorders (e.g., single gene ailments such as Rett Syndrome, Fragile X or tuberous sclerosis, or identified rare variants with large effect in the ASD population) to promote the identification and examination of common molecular pathways or neurocircuits Application of novel multimodal imaging techniques for longitudinal studies in utero and throughout the lifespan in models with relevance to ASD Identification and characterize sensitive periods of improvement relevant to the risk for developing ASD Advancement and application of models for understanding the joint contribution of environmental exposures and genetic variation to ASD
Pre-Clinical Treatment Growth – Targeted Therapeutics

Existing medications do not adequately treat the range of core deficits in ASD.  Medications partially improve some of the behavioral and affective symptoms associated with ASD, but none have been shown in controlled trials to improve social behavior or communication.  Novel approaches are needed to identify effective treatment targets for therapeutic discovery both for treatment and to prevent the developmental emergence of symptoms of ASD. 

Examples of relevant study of interest include but are not minimal to the following:
Identification and validation of targets for drug discovery for ASD including preclinical demonstration of ‘proof-of-concept’ for a new therapeutic candidate in ASD Design and optimization of compounds directed toward altering, modifying, or regulating targets implicated in the pathophysiology of ASD Advancement, validation, and implementation of assays that permit the preliminary screening of candidate compounds, including biochemical and cellular assays, modified model organisms, and electrophysiological or behavioral systems that reflect core deficits in ASD Growth, validation, and implementation of in vivo (mammalian, non-mammalian) and cell/tissue models that permit further evaluation of potential efficacy and safety of promising interventions for ASD.  Examples include behavior models and/or model systems (genetic, chemical, other manipulations) that recapitulate critical features of ASD, particularly social deficits and repetitive behaviors, or underlying pathogenic mechanisms Application of emerging induced pluripotent cell and technologies to define the impact of novel compounds or existing medications on cellular responses across individuals expressing variable disease profiles, with the goal of identifying new molecular targets for treatment growth Characterization of candidate therapeutics for pharmacokinetic properties and safety profiles in relevant assays of absorption, distribution, metabolism, excretion, and toxicity (ADMET)
Treatment and Intervention

A wide range of treatments and interventions are in use to deal with the core symptoms and comorbid conditions associated with ASD, but most of these have not been rigorously studied.  There is a need for demonstration of efficacy of existing widely-used but untested treatments, as well as for emerging treatments or interventions in improvement, taking into account the need for interventions for individuals across the lifespan, and the knowledge that symptoms change in expression and severity across growth.  Given the vast heterogeneity in this population, efficacious methods are needed for core symptoms of various levels of severity, for addressing comorbid conditions, for personalizing treatment, and for matching individuals to appropriate interventions.  Studies are needed to rigorously test the efficacy of treatments and interventions that tackle pressing needs and gaps in the range of available evidence-based treatments and interventions for individuals with ASD across the lifespan.   Of interest are studies of treatments and interventions for which preliminary and pilot data on safety, tolerability, and feasibility already exist.  Programs should present strong evidence that a fully-powered randomized controlled trial is feasible within the constraints of the two-year award.  

Examples of relevant research of interest include but are not limited to the following:
Adaptation of evidence-based interventions to reduce or ameliorate symptoms, and improve adaptive functioning, in older children, adolescents, and adults with ASD Interventions for infants and toddlers with early signs of ASD Multi-site randomized controlled trials of comprehensive early interventions, addressing core symptoms, family functioning, and community involvement Randomized, controlled trials of medications targeting core symptoms of social and communication dysfunction in individuals with ASD Adapted or augmented treatments for individuals who do not respond to Applied Behavior Analysis (ABA) or other evidence-based interventions Integration/Implementation of pharmacogenomics approaches in the design and conduct of clinical trials for ASD Growth of validated outcome measures for use in randomized controlled trials of treatments and interventions for ASD Studies to develop interventions for sibling of people with ASD and other high-risk populations with the goal of reducing risk of recurrence
Services Research

Studies of existing individual and family supports and providers are needed to establish their effectiveness in optimizing outcomes for persons with ASD across the lifespan (e.g., childhood, adolescence, transition to adulthood, and adulthood).  Areas of interest include services addressing ongoing daily needs, as well as those addressing special needs during critical periods (e.g. times of transition) or times of crisis.  Companies analysis studies that target optimizing availability, access, organization, financing and quality of care are encouraged. 

Examples of relevant study of interest include but are not constrained to the following:
Studies to test the effectiveness of solutions and supports in improving access to ASD interventions across the lifespan Studies to test the effectiveness of programs to foster broader screening and follow-up strategies to improve diagnosis and involvement in appropriate programs and services Studies to test the effectiveness of solutions to deal with the needs of transition-age youth and adults with ASD including vocational rehabilitative solutions, housing and education/training programs Studies to test the effectiveness of companies to facilitate and support comprehensive medical care for individuals with ASD, including preventive care and treatment of acute illnesses, management of sleep dysfunction, coexisting challenging behaviors or psychiatric conditions, and associated medical problems Analysis to develop strategies to merge or link administrative and/or other surveillance databases to systematically track the involvement of people living with ASD in health care, education and social companies Cost/cost benefit analyses on provision of solutions and interventions over the lifespan with regard to long-term benefits including employment, productivity, and the need for federal/state guidance Analysis to understand the impact on ASD outcomes of system reforms including quality improvement initiatives and innovative financing reform (e.g., Medicaid waivers) Pilot studies of companies interventions aimed at overcoming access barriers associated with: rural as well as other under-resourced areas, racial or ethnic minority status, low educational levels of parents Pilot studies of strategies to deal with solutions needs for ASD faced by military families
The Nationwide Database for Autism Investigation (NDAR) has been established to serve the autism study community as a common platform for exchanging data, tools, and research-related details ( and to serve as a portal to and for the broad autism study community. Autism researchers funded under this Request for Applications who are collecting phenotypic, genetic, or image data from humans are expected to share those data via NDAR, making use of its global unique identifier (GUID) technology.  Such data that are generated by grants funded under this Request for Purposes are expected to be quality-certified before submission, and checked again after submission, by investigators.  Phenotypic data are to be submitted every January 15 and July 15, and all other data submitted before the end of the project period (see data submission info agreement at NDAR staff will work with investigators to help them submit data other than phenotypic, genetic, or image.  For answers to frequently asked questions, contact details for the NDAR manager, and also other info, please see

See Section VIII, Other Info - Required Federal Citations, for laws and policies related to this announcement.

Section II. Award Information

1. Mechanism of Support

This FOA will use the NIH Investigation Project Grant (R01) award mechanism. The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.  

This FOA uses “Just-in-Time” data concepts (see SF424 (R&R) Application Guide). It also uses the modular as well as the non-modular budget formats (see Specifically, a U.S. organization submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs) need to use the PHS398 Modular Budget component.

U.S. applicants requesting more than $250,000 in annual direct costs need to complete and submit budget requests making use of the Study & Connected Budget component.

2. Funds Available

This initiative supported by funds provided to the NIH under the American Recovery & Reinvestment Act of 2009 (“Recovery Act” or “ARRA”), Public Law 111-5. The NIH intends to commit approximately $57,000,000 in total costs for FY2009 and FY2010 to support approximately 40-50 grants in response to this FOA and the companion Collaborative R01, R21, and R34/Collaborative R34 FOAs, contingent upon the submission of a sufficient amount of scientifically meritorious applications. The total project period for an application submitted in response to this R01 FOA may not exceed two years.

Because the nature and scope of the proposed study will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the participating NIH Institutes and Centers (“IC(s)”) provide support for this program, awards pursuant to this funding possibility are contingent upon the availability of funds.


Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004.


This program is supported by funds provided to the NIH under the Recovery Act.  The purpose of the Recovery Act is to stimulate the American economy through job preservation and creation, infrastructure investment, energy efficiency and science, and other means.  Consistent with these goals, domestic (United States) institutions/organizations planning to submit purposes that include foreign parts should be aware that requested funding for any foreign component should not exceed 10% of the total requested direct costs or $25,000 (aggregate total for a subcontract or multiple subcontracts), whichever is less.

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

1.A. Eligible Institutions

The following organizations/institutions are eligible and encouraged to apply. Consistent with the purposes of the Recovery Act (in particular, to preserve and create jobs and promote economic recovery in the United States, and to provide investments needed to increase economic efficiency by spurring technological advances in science and wellbeing), applicants have to be a domestic (United States) institution/organization. The United States institution/organization must be located in the 50 states, territories and possessions of the United States,Windows 7 Product Key, Commonwealth of Puerto Rico, Trust Territory of the Pacific Islands, or District of Columbia. NIH encourages applications from all interested organizations/institutions, including those from Institutional Advancement Award (IDeA) states and Academic Research Enhancement Award (AREA)-eligible institutions. Foreign organizations/institutions are not permitted as the applicant organization.
Public/State Controlled Institutions of Higher Education 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 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) Small Businesses For-Profit Organizations (Other than Small Businesses) State Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribally Designated Organizations County Governments City or Township Governments Special District Governments Independent School Districts Public Housing Authorities/Indian Housing Authorities U.S. Territory or Possession Indian/Native American Tribal Governments (Other than Federally Recognized) Regional Organizations Other(s): Eligible Agencies of the Federal Government Faith-based or Community-based Organizations
1.B. Eligible Individuals

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed investigation as the PD/PI 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.

More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application for projects that require a “team science” approach and therefore clearly do not fit the single-PD/PI model. Additional details on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at All PDs/PIs has to be registered in the NIH electronic Analysis Administration (eRA) Commons prior to the submission of the application (see for instructions).

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Programs for grants with multiple PDs/PIs will require additional info, as outlined in the instructions below. When considering the multiple PD/PI option, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application.  Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further details on multiple PDs/PIs, please see

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

Number of Purposes. Applicants may submit more than one application, provided each application is scientifically distinct.

Resubmissions.  Resubmission apps are not permitted in response to this FOA.

Renewals.  Renewal purposes are not permitted in response to this FOA.

Section IV. Application and Submission Information

To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, use the “Apply for Grant Electronically” button in this FOA or link to and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:
Grants.gov ( and  eRA Commons (
PDs/PIs should work with their institutions/organizations to make sure they are registered in the NIH eRA Commons.

Several additional separate actions are required before an applicant can submit an electronic application, as follows:  

1) Organizational/Institutional Registration in Grants.gov/Get Registered
Your organization will need to obtain a Data Universal Amount System (DUNS) amount and register with the Central Contractor Registration (CCR) as aspect of the Grants.gov registration process. If your organization does not have a Taxpayer Identification Number (TIN) or Employer Identification Range (EIN), allow for extra time. A valid TIN or EIN is necessary for CCR registration. The CCR also validates the EIN against Internal Revenue Service records, a step that will take an additional one to two business days. Direct questions regarding Grants.gov registration to:
Grants.gov Customer Support 
Contact Center Phone: 800-518-4726
Business Hours: M-F 7:00 a.m. - 9:00 p.m. Eastern Time
Email support@grants.gov     
2) Organizational/Institutional Registration in the eRA Commons
To find out if an organization is already Commons-registered, see the "List of Grantee Organizations Registered in NIH eRA Commons.” Direct questions regarding the Commons registration to:
eRA Commons Help Desk
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Business hours M-F 7:00 a.m. – 8:00 p.m. Eastern Time
Email commons@od.nih.gov
3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.
The individual(s) designated as PDs/PIs on the application have to be registered also in the NIH eRA Commons. In the case of multiple PDs/PIs, all PDs/PIs have to be registered and be assigned the PI role in the eRA Commons prior to the submission of the application. Each PD/PI need to hold a PD/PI account in the Commons. Applicants should not share a Commons account for both an Authorized Organization Representative/Signing Official (AOR/SO) role and a PD/PI role; however, if they have both a PD/PI role and an NIH Internet Assisted Review (IAR) role, both roles should exist under one Commons account. When multiple PDs/PIs are proposed, all PDs/PIs at the applicant organization should be affiliated with that organization. PDs/PIs located at another institution need not be affiliated with the applicant organization,Microsoft Office 2007 Professional, but must be affiliated with their own organization to be able to access the Commons. This registration/affiliation have to be done by the AOR/SO or his/her designee who is already registered in the Commons.
Both the PDs/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

Several steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic programs only from organizations that have completed all necessary registrations.

1. Request Application Info

Applicants should download the SF424 (R&R) application forms and the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.

For further help, contact GrantsInfo -- Telephone 301-435-0714; Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY: (301) 451-5936

2. Content and Form of Application Submission

Prepare all purposes making use of the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide for this FOA by way of Grants.gov/Apply.

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. Some fields within the SF424 (R&R) application parts, although not marked as mandatory, are necessary for processing (e.g., the “Credential” log-in field of the “Research & Associated Senior/Key Person Profile” component ought to contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional info, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”

The SF424 (R&R) application has several parts. Some elements are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY includes all applicable parts, required and optional. A completed application in response to this FOA includes the data in the following elements:

Required Elements:
SF424 (R&R) (Cover component)
Research & Associated Project/Performance Site Locations
Analysis & Related Other Project Details
Study & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget or Analysis & Connected Budget, as appropriate (See Section IV.6., “Special Instructions,” regarding appropriate required budget component.)  

Optional Components:
PHS398 Cover Letter File
Study & Associated Subaward Budget Attachment(s) Form

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the "Contact” PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI should meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered in item 15 of the SF424 (R&R) Cover component. All other PDs/PIs should be listed in the Research & Associated Senior/Key Person component and assigned the project role of “PD/PI.” Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI has to be included in the “Credential” field of the Research & Related Senior/Key Person component. Failure to include this data field will cause the application to be rejected.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan: For programs designating multiple PDs/PIs, a new section of the analysis plan, entitled “Multiple PD/PI Leadership Plan” [Section 14 of the Research Plan Component in the SF424 (R&R)], have to be included. A rationale for choosing a multiple PD/PI approach should be described.  The governance and organizational structure of the leadership team and the study project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs along with other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan.  In the event of an award, the requested allocations may be reflected in a footnote on the Recognize of Award (NoA).

Applications Involving a Single Institution

When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide.

Applications Involving Multiple Institutions 

When multiple institutions are involved, one institution have to be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget making use of the Analysis & Related Budget component. All other institutions should have their individual budgets attached separately to the Analysis & Relevant Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form. 

When submitting a modular budget, the prime institution completes the PHS398 Modular Budget component only. Information concerning the consortium/subcontract budget is provided in the budget justification. Separate budgets for each consortium/subcontract grantee are not required when using the Modular budget format. See Section 5.4 of the Application Guide for further instruction regarding the use of the PHS398 Modular Budget component.

3. Submission Dates and Times

See Section IV.3.A. for details.


3.A. Submission, Review, and Anticipated Start Dates
Opening Date: April 12, 2009 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): April 12, 2009
Application Due Date(s): May 12, 2009
Peer Review Date(s): July 2009
Council Review Date(s): August 2009
Earliest Anticipated Start Date(s): September 30, 2009

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following data:
Descriptive title of proposed research. Name, deal with, and telephone range of the PD(s)/PI(s). Names of other key personnel. Taking part institutions. Quantity and title of this funding option.
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the info that it contains allows IC staff to estimate and plan for the potential review workload.

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Lisa Gilotty, Ph.D.
Division of Developmental Translational Research
Countrywide Institute of Mental Wellness
6001 Executive Boulevard, Room 6179, MSC 9617
Bethesda, MD 20892-9617
Telephone: (301) 443-3825
Fax: (301) 480-4415
Email: gilottyl@mail.nih.gov

3.B. Submitting an Application Electronically to the NIH

To submit an application in response to this FOA, applicants should access this FOA via and follow Steps 1-4. Note:  Applications must only be submitted electronically.  PAPER Purposes WILL NOT BE ACCEPTED. 

Applicants are requested to notify the NIMH Referral Office by email NIMHReferral@mail.nih.gov when the application has been submitted.  Please include the FOA quantity and title, PD/PI name, and title of the application.

3.C. Application Processing

Applications may be submitted on or after the opening date and have to be successfully received by Grants.gov no later than 5:00 p.m. local time of the applicant institution/organization on the application due date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the due date(s) and time, the application may be delayed in the review process or not reviewed.

Once an application package has been successfully submitted via Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two weekdays (Monday – Friday, excluding Federal holidays) to view the application image to determine if any further action is necessary.
If everything is acceptable, no further action is necessary. The application will automatically move forward to the Division of Receipt and Referral in the Center for Scientific Review (CSR) for processing after two weekdays, excluding Federal holidays. Prior to the submission deadline, the AOR/SO can “Reject” the assembled application and submit a changed/corrected application within the two-day viewing window. This option should be used if it is determined that some aspect of the application was lost or did not transfer correctly during the submission process, the AOR/SO will have the option to “Reject” the application and submit a Changed/Corrected application. In these cases, please contact the eRA Help Desk to ensure that the issues are addressed and corrected. Once an application is rejected by the AOR/SO, applicants should follow the instructions for correcting errors in Section 2.12, including the requirement for cover letters on late applications. The “Reject” feature should also be used if you determine that warnings are applicable to your application and need to be addressed now. Remember, warnings do not stop further application processing. If an application submission results in warnings (but no errors), it will automatically move forward after two weekdays if no action is taken. Some warnings may need to be addressed later in the process. If the two-day window falls after the submission deadline, the AOR/SO will have the option to “Reject” the application if, due to an eRA Commons or Grants.gov system issue, the application does not correctly reflect the submitted application package (e.g., some aspect of the application was lost or didn’t transfer correctly during the submission process). The AOR/SO should first contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine the best course of action. NIH will not penalize the applicant for an eRA Commons or Grants.gov system issue. If the AOR/SO chooses to “Reject” the image after the submission deadline for a reason other than an eRA Commons or Grants.gov system failure, a changed/corrected application still can be submitted, but it will be subject to the NIH Policy on Late Submissions of Grant Programs (NOT-OD-05-030) and may not be accepted. The reason for this delay should be explained in the cover letter attachment. Both the AOR/SO and PD/PI will receive e-mail notifications when the application is rejected or the application automatically moves forward in the process after two weekdays.
Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the IC. Incomplete and non-responsive purposes will not be reviewed.

There will be an acknowledgement of receipt of apps from Grants.gov and the Commons. The submitting AOR/SO receives the Grants.gov acknowledgments. The AOR/SO and the PI receive Commons acknowledgments. Details relevant to the assignment of an application to a Scientific Review Group is also in the Commons. 

Note: Since email can be unreliable, it is the responsibility of the applicant to check periodically on the application status in the Commons.

The NIH will not accept any application in response to this funding chance that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an “Introduction” describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review, as indicated in the NIH Grants Policy Statement.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, as well as other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or renewal award if such costs: 1) are necessary to conduct the project, and 2) would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee should obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or renewal award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing ought to not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project (see the NIH Grants Policy Statement).

6. Other Submission Requirements and Data

PD/PI Credential (e.g., Agency Login)

The NIH requires the PD(s)/PI(s) to fill in his/her Commons User ID in the “PROFILE – Project Director/Principal Investigator” section, “Credential” log-in field of the “Research & Relevant Senior/Key Person Profile” component.

Organizational DUNS

The applicant organization ought to include its DUNS amount in its Organization Profile in the eRA Commons. This DUNS range ought to match the DUNS range provided at CCR registration with Grants.gov. For additional info, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Programs.”

Special Instructions for PHS398 Analysis Plan Component (Section 5.5 of SF424 (R&R) Application)

Research Plan: The Analysis Plan is constrained to a total of 12 pages.

PHS398 Study Plan Component Sections

Item Amount and Title

Instructions

1. Introduction to Application

Omit (N/A: Resubmissions and Revisions not allowable)

2. Specific Aims

One page maximum. Separate PDF attachment

3. Background and Significance

Combined in a single PDF in item 5

4. Preliminary Studies/Progress Report

Combined in a single PDF in item 5

5. Investigation Design and Methods

Item 5 consists of Items 3-5 and is limited to 12 pages. Attach the 12-page Investigation Plan encompassing items 3-5 as a single PDF document. Figures and illustrations may be included but ought to fit within the specified page limit. Do not include links to Web sites for further data. Do not include animations.

Excluded from the 12 -page Investigation Plan limitation are the following items:
Specific Aims (1 page maximum) Inclusion Enrollment Report Protection of Human Subjects Inclusion of Women and Minorities Targeted/Planned Enrollment Inclusion of Children Vertebrate Animals Select Agent Research MPI Leadership Plan Consortium/ Contractual Arrangements Letters of Support Resource Sharing Plans
Note the 12-page limit also excludes the Project Summary/Abstract; Bibliography and Literature Cited; and Biographical Sketches (separate PDFs).

All attachments has to be provided to NIH in PDF format, filenames should be included with no spaces or special characters, and a .pdf extension must be used.   

Appendix Materials

Applicants should follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide (See

Do not use the Appendix to circumvent the page limitations of the Analysis Plan component. An application that does not comply with the required page limitations may be delayed in the review process.
Resource Sharing Plan(s)
NIH considers the sharing of unique investigation resources developed by way of NIH-sponsored research an important means to enhance the value and further the advancement of the investigation. When resources have been developed with NIH funds and the associated investigation findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this have to be explained in the Resource Sharing section of the application (see

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final analysis data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact (see Data-Sharing Policy or

 (b) Sharing Model Organisms: Regardless of the amount requested, all programs in which the advancement of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and connected resources, or state appropriate reasons why such sharing is restricted or not possible (see Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.)

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible.  A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (e.g., blood pressure or weight) or the presence or absence of a disease or condition.  For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies (NOT-OD-07-088) and

(d) Sharing Human Data via the Countrywide Database for Autism Investigation: The Countrywide Database for Autism Analysis (NDAR) has been established to serve the autism study community as a common platform for exchanging data, tools, and research-related details ( and to serve as a portal to and for the broad autism investigation community. Autism researchers funded under this Request for Programs who are collecting phenotypic, genetic, or image data from humans are expected to share those data via NDAR, employing its global unique identifier (GUID) technology.  Such data that are generated by grants funded under this Request for Apps are expected to be quality-certified before submission, and checked again after submission, by investigators.  Phenotypic data are to be submitted every January 15 and July 15, and all other data submitted before the end of the project period (see data submission details agreement at NDAR staff will work with investigators to help them submit data other than phenotypic, genetic, or image.  For answers to frequently asked questions, contact details for the NDAR manager, along with other details, please see

Section V. Application Review Information

1. Criteria 

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability.  As part of this mission, apps submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral analysis are evaluated for scientific and technical merit through the NIH peer review system. 

Applications that are complete and responsive to this FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by (NIMH) and in accordance with NIH peer review procedures ( using the review criteria stated below.

As part of the scientific peer review, all purposes will:
Undergo a selection process in which only those apps deemed to have the highest scientific and technical merit will be discussed and assigned a priority score; Receive a written critique; and Receive a second level of review by the appropriate countrywide advisory council or board.
Overall Impact. Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five core review criteria, and additional review criteria (as applicable for the project proposed).  Reviewers will also factor into their assessment the project’s responsiveness to the short-term goals and objectives of the Strategic Plan for ASD Research as defined by the Interagency Autism Coordinating Committee (

Core Review Criteria.  Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each.  An application does not need to be strong in all categories to be judged likely to have major scientific impact.  For example, a project that by its nature is not innovative may be essential to advance a field.

Significance.  Does the project handle an important problem or a critical barrier to progress in the field?  If the aims of the project are achieved, how will scientific knowledge, technological advances, technical capability, clinical practice, and/or wellbeing be improved?  How will successful completion of the aims change the concepts, methods, technologies, treatments, solutions, or preventative interventions that drive this field? Are the specific aims of the project responsive to the short-term goals and objectives of the IACC Strategic Plan for ASD Research?

Investigator(s).  Are the PD/PIs, collaborators, and other researchers well suited to the project?  If Early Stage Investigators or New Investigators, do they have appropriate experience and training?  If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)?  If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation.  Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions?  Are the concepts, approaches or methodologies, instrumentation, technological developments, or interventions novel to one field of study or novel in a broad sense?  Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach.  Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project?  Are potential problems, alternative strategies, and benchmarks for success presented?   If the project is in the early stages of growth, will the strategy establish feasibility and will particularly risky aspects be managed?
If the project involves clinical investigation, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both ######es/genders, as well as the inclusion of children, justified in terms of the scientific goals and analysis strategy proposed?

Environment.  Will the scientific environment in which the work will be done contribute to the probability of success?  Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed?  Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? 

2.A. Additional Review Criteria

As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, but will not give separate scores for these items.

Protections for Human Subjects.  For analysis that involves human subjects but does not involve one of the six categories of study that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For study that involves human subjects and meets the criteria for one or more of the six categories of analysis that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

Inclusion of Women, Minorities, and Children.  When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

Vertebrate Animals.  The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, ######, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia.

Biohazards.  Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

2.B. Additional Review Considerations

As applicable for the project proposed, reviewers will tackle each of the following items, but will not give scores for these items and should not consider them in providing an overall impact/priority score.

Budget and Period Support.  Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed analysis.

Select Agent Study. Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed investigation, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans.  Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable:
Data Sharing Plan. [ Sharing Model Organisms. [ Genome Wide Association Studies (GWAS). [ Nationwide Database for Autism Research (NDAR) (
The NIH will not accept appeals of the review process outcome for applications in response to this FOA. See NOT-OD-09-054, Recovery Act of 2009: NIH Review Criteria, Scoring System, and Suspension of Appeals Process.

Applications submitted in response to this FOA will compete for available funds with all other recommended applications submitted in response to this FOA. The following will be considered in making funding decisions:
Scientific merit of the proposed project as determined by peer review. Availability of funds. Relevance of the proposed project to program priorities.
3. Anticipated Announcement and Award Dates

Not Applicable

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the NIH eRA Commons. 

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General. In addition, as component of “just-in-time” details for those Recovery Act awards, for any modular budget application, a detailed budget will be required prior to award.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

The terms of the NoA will reference the requirements of the Recovery Act.

In addition to the standard NIH terms of award, all awards will be subject to the HHS Standard Terms and Conditions for Recovery Act awards.  The full text of these terms approved for NIH awards can be found in the following document: Standard Terms and Conditions for AARA Awards.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Section IV.5., “Funding Restrictions.”       

In addition, recipients of Recovery Act funds are reminded that such funds must be separately tracked and monitored independently of any non-Recovery Act funding. Additional terms may be applied to the actual award.

2. Administrative and Countrywide Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as aspect of the NoA. For these terms of award, see the NIH Grants Policy Statement Aspect II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities.

3. Reporting

Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

In addition, grantees ought to comply with the requirements set forth in the Recovery Act, including, but not limited to, the reporting requirements described in Section 1512 of the Act, as well as applicable OMB guidance regarding the use of Recovery Act funds.  As noted above, grantees should also comply with the HHS Standard Terms and Conditions for Recovery Act awards.  The full text of these terms approved for NIH awards can be found in the following document: Standard Terms and Conditions for AARA Awards.

Recovery Act-related reporting requirements will be incorporated as a special term of award.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding chance and welcome the option to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research (program), peer review, and financial or grants management issues:

1. Scientific/Research Contact(s):

Lisa Gilotty, Ph.D.
Division of Developmental Translational Research
Countrywide Institute of Mental Well being
6001 Executive Boulevard, Room 6179, MSC 9617
Bethesda, MD 20892-9617
Telephone: (301) 443-3825
Fax: (301) 480-4415
Email: gilottyl@mail.nih.gov

Judith Cooper, Ph.D.
National Institute on Deafness as well as 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 Youngster Wellness 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.
Countrywide Institute of Neurological Ailments and Stroke
6001 Executive Boulevard, Room 2212, MSC 9250
Bethesda, MD  20892-9250
Telephone:  (301) 496-5821
FAX:  (301) 480-1080
Email:  hirtzd@ninds.nih.gov

Cindy P. Lawler, Ph.D.
Program Administrator
Cellular, Organ, Systems and Pathobiology Branch
Division of Extramural Study and Training
Countrywide Institute of Environmental Wellbeing Sciences
P.O. Box 12233, Mail Drop K3-15
Investigation Triangle Park, NC  27709
Telephone:  (919) 316-4671
FAX:  (919) 541-5064
Email:  lawler@niehs.nih.gov

2. Peer Review Contact(s):

David Armstrong, Ph.D.
Division of Extramural Activities
National Institute of Mental Wellbeing
6001 Executive Boulevard, Room 6138, MSC 9606
Bethesda, MD 20892-9606
Telephone: (301)443-3534
Fax:  (301)443-4720
Email:  armstrda@mail.nih.gov

3. Financial/Grants Management Contact(s):

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

Bryan S. Clark, M.B.A.
Chief Grant Managements Officer
The Eunice Kennedy Shriver Countrywide Institute of Youngster Well being and Human Improvement (NICHD)
6100 Executive Boulevard, Room 8A01A, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: (301) 435-6975
Fax: (301) 402-0915
Email: clarkb1@mail.nih.gov

Christopher Myers
Chief, Grants Management Office
Countrywide Institute on Deafness and other Communication Disorders
6120 Executive Boulevard, EPS Room 400-B, MSC 7180
Bethesda, MD  20892-7180
Telephone:  (301) 402-0909
Fax:  (301) 402-1758
Email:  myersc@nidcd.nih.gov

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

Tijuanna DeCoster, MPA
Chief, Grants Management Officer
Nationwide Institute of Neurological Problems and Stroke
6001 Executive Boulevard, Room 3258, MSC 9537
Bethesda, MD  20892-9537
Telephone:  (301) 496-9231
Fax:  (301) 402-0219
Email:  decostert@mail.nih.gov

Section VIII. Other Information

Required Federal Citations

The American Recovery And Reinvestment Act of 2009 (Pub. L. No. 111-5):

Standard Terms and Conditions for Recovery Act Awards: The full text of these terms approved for NIH awards can be found in the following document:

Use of Animals in Analysis:
Recipients of PHS support for activities involving live, vertebrate animals should comply with PHS Policy on Humane Care and Use of Laboratory Animals ( as mandated by the Well being Analysis Extension Act of 1985 ( and the USDA Animal Welfare Regulations ( as applicable.

Human Subjects Protection:
Federal regulations (45 CFR 46) require that apps 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 study to the subjects and others, and the importance of the knowledge gained or to be gained (

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). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (“NIH Policy for Data and Safety Monitoring,” NIH Guide for Grants and Contracts,

Sharing Analysis Data:
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 ( Investigators should seek guidance from their institutions, on issues related to institutional policies and local institutional review board (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.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence wellness and disease by way of a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All apps, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional data, see

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important study resources including the sharing of model organisms for biomedical study (see At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh-Dole Act (see the NIH Grants Policy Statement. Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism analysis resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all purposes where the advancement of model organisms is anticipated.

Access to Study Data through the Freedom of Data Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data by means of the Freedom of Data 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 by means of FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at Applicants may wish to place data collected under this funding opportunity 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 also other human subjects procedures given the potential for wider use of data collected under this award.

Inclusion of Women And Minorities in Clinical Analysis:
It is the policy of the NIH that women and members of minority groups and their sub-populations has to be included in all NIH-supported clinical study 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 investigation. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical investigation should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research” ( a complete copy of the updated Guidelines is available at The amended policy incorporates: the use of an NIH definition of clinical analysis; 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 SF424 (R&R) application; 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 ######/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators should report annual accrual and progress in conducting analyses, as appropriate, by ######/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Analysis:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical analysis, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in analysis involving human subjects (

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 purposes for analysis involving human subjects and individuals designated as key personnel. The policy is available at

Human Embryonic Stem Cells (hESC):
Criteria for Federal funding of research on hESCs can be found at and at Only research employing hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding ( 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.

NIH Public Access Requirement:
In accordance with the NIH Public Access Policy, investigators funded by the NIH must submit or have submitted for them to the Countrywide Library of Medicine’s PubMed Central (see an electronic version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no later than 12 months after the official date of publication. The NIH Public Access Policy is available at ( For more details, see the Public Access webpage at

Standards for Privacy of Individually Identifiable Wellness Details:
The Division of Wellness and Human Companies (HHS) issued final modification to the "Standards for Privacy of Individually Identifiable Wellbeing Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Wellness Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable wellness information, and is administered and enforced by the HHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website ( provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Data on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and investigation contracts can be found at

URLs in NIH Grant Apps or Appendices:
All programs and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission identification numbers must be used for publicly accessible on-line journal articles. Publicly accessible on-line journal articles or PMC articles/manuscripts accepted for publication that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference in either the Bibliography & References Cited section, the Progress Report Publication List section, or the Biographical Sketch section of the NIH grant application. A URL or PMC submission identification number citation may be repeated in each of these sections as appropriate. There is no limit to the amount of URLs or PMC submission identification numbers that can be cited.

Healthy People 2010:
The Public Well being Service (PHS) is committed to achieving the wellbeing promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is associated to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at and is not subject to the intergovernmental review requirements of Executive Order 12372. Awards are made under Sections 301 and 405 of the Public Well being Service Act, as amended (42 USC 241 and 284) and are subject to 42 CFR Component 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, as well as other considerations described in the NIH Grants Policy Statement.

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,Office 2010 Download, library, day care, wellness care, or early childhood improvement services are provided to children. This is consistent with the PHS mission to protect and advance the physical and psychological health of the American people.

Loan Repayment Programs:
NIH encourages apps for educational loan repayment from qualified wellness professionals who have made a commitment to pursue a study career involving clinical, pediatric, contraception, infertility, and well being disparities relevant areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a study career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP apps are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees need to commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the study. For further details, please see: