RESEARCH ON AUTISM AND AUTISM SPECTRUM DISORDERS RELEASE DATE: April 2, 2004 PA NUMBER: PA-04-085 January 3, 2007 - Effective with the February 5, 2007 submission date, all R01 applications must be submitted through using the electronic SF424 (R&R) application. Accordingly, the R01 portion of this funding opportunity expires on January 3, 2007. Unsolicited or investigator-initiated R01 electronic SF424 (R&R) applications may be submitted through the Research Project Grant (Parent R01) announcement. March 2, 2006 (NOT-OD-06-046) Effective with the June 1, 2006 submission date, all R03, R21, R33 and R34 applications must be submitted through using the electronic SF424 (R&R) application. This announcement will stay active for only the May 1, 2006 AIDS and AIDS-related application submission date for these mechanisms. The non-AIDS portion of this funding opportunity for these mechanisms expires on the date indicated below. Other mechanisms relating to this announcement will continue to be accepted using paper PHS 398 applications until the stated expiration date below, or transition to electronic application submission. Replacement R03 (PA-06-391) and R21 (PA-06-392) funding opportunity announcements have been issued for the submission date of June 1, 2006 and submission dates for AIDS and non-AIDS applications thereafter. EXPIRATION DATE for R03 and R21 Non-AIDS Applications: March 2, 2006 EXPIRATION DATE for R03 and R21 AIDS and AIDS-Related Applications: May 2, 2006 EXPIRATION DATE for R01 Non-AIDS Applications: November 2, 2006 EXPIRATION DATE for R01 AIDS and AIDS-Related Applications: January 3, 2007 Department of Health and Human Services (DHHS) PARTICIPATING ORGANIZATION: National Institutes of Health (NIH) ( COMPONENTS OF PARTICIPATING ORGANIZATION: National Institute of Mental Health (NIMH) ( National Institute on Deafness and Other Communication Disorders (NIDCD) ( National Institute of Child Health and Human Development (NICHD) ( National Institute of Neurological Disorders and Stroke (NINDS) ( National Institute of Environmental Health Sciences (NIEHS) ( National Institute of Nursing Research (NINR) ( CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S): 93.113, 93.115, 93.173, 93.242, 93.361, 93.865, 93.853 THIS PA CONTAINS THE FOLLOWING INFORMATION o Purpose of the PA o Research Objectives o Mechanism(s) of Support o Eligible Institutions o Individuals Eligible to Become Principal Investigators o Special Requirements o Where to Send Inquiries o Submitting an Application o Supplementary Instructions o Peer Review Process o Review Criteria o Award Criteria o Required Federal Citations PURPOSE OF THIS PA This PA replaces PA-01-051. The purpose of this program announcement is to encourage grant applications for the support of research designed to elucidate the diagnosis, epidemiology, etiology, genetics, treatment, and optimal means of service delivery in relation to Autistic Disorder ("autism") and autism spectrum disorders (Rett's Disorder, Childhood Disintegrative Disorder, Asperger's Disorder, Pervasive Developmental Disorder-Not Otherwise Specified, or "Atypical Autism"). This PA is meant to support the broad research goals of the Autism Research Matrix ( In February 2003, Congress requested that the Department of Health and Human Services (HHS) develop a set of autism research goals and activities for the next several years (House Report 109-10). Input into this activity included a meeting of autism investigators with a range of scientific expertise, as well as input from community members. Preparation for specifying this matrix involved a two-day meeting of an expert panel of scientists; public presentation and discussion of a draft matrix at the Autism Summit Conference in Washington DC on November 20, 2003; and adoption of the matrix by the Federal Interagency Autism Coordinating Committee (IACC). RESEARCH OBJECTIVES Current classification systems (e.g., DSM-IV) include five separate diagnoses under the Pervasive Developmental Disorders: Autistic Disorder, Rett's Disorder, Childhood Disintegrative Disorder, Asperger's Disorder, and Pervasive Developmental Disorder Not Otherwise Specified. Collectively, these Pervasive Developmental Disorders are often referred to as Autism Spectrum Disorders . These disorders share a cluster of impairments in reciprocal social interaction and communication and/or the presence of stereotyped behavior, interests, and activities. These complex disorders are usually of lifelong duration and affect multiple aspects of development, learning, and adaptation in the community, and thus represent a pressing public health need. The etiologies of these disorders are poorly understood, but are thought to include genetic, metabolic, immunologic, or infectious or other environmental influences. Clinical research involving these disorders requires well-integrated, multi- disciplinary, methodologically-rigorous scientific approaches and access to a sufficient number of well-characterized patients with these disorders. Basic research into the pathophysiology of autism and autism spectrum disorders, including research on brain mechanisms and genetics, is of special interest. Also of high priority are clinical and applied investigations that may lead to the development of diagnostic research instruments, treatments, and intervention strategies. Specific areas of interest thus include epidemiology, early identification and diagnosis, genetic studies, brain mechanisms, communication skills, cognitive neuroscience, psychosocial (behavioral) interventions, pharmacological and other biological interventions, and support and rehabilitative services across the life-span, including adulthood and the transition to adulthood. Areas of interest include, but need not be limited to, the following: o Epidemiology: Studies of the genetic and environmental epidemiology of autism to determine risk and protective processes in the etiology of autism, including environmental exposures during pregnancy and early childhood; longitudinal studies of high-risk populations; epidemiologic research on interactive genetic and environmental processes that increase or decrease risk for autism; research on the expression of the full range of autism spectrum disorders; studies of their developmental course across the life-span; studies that characterize the range of expression within families; and research on co-occurring features, especially research that characterizes and quantifies risk and protective processes associated with co-occurrence. Also of interest are clinical epidemiologic studies of autism spectrum disorders in clinical settings, including studies of clinical decision- making in personal-encounter care for individuals and families. o Screening, Early Identification, and Diagnosis: Key diagnostic and phenotypic features associated with various stages of development; development of new screening tools for use in a variety of settings; assessment of comorbid features including hyperactivity, attentional dysfunctions, epilepsy, and obsessive and compulsive symptoms; the creation of new measures to be used in longitudinal studies and measures that further differentiate the subtypes of autism spectrum disorders; and, developmental factors relevant to reliable and valid diagnosis. o Genetic Studies: Family-based association analysis and other linkage disequilibrium approaches that aim to identify specific susceptibility genes; studies of epigenetic mechanisms and long range control of gene expression; high- resolution mapping and positional cloning studies; resolution of locus heterogeneity; analysis of the interaction of autism susceptibility genes with environmental exposures and/or genes responsive to environmental insult; testing for potential candidate genes. An area of particular interest is the effect of genetic factors on therapeutic drug response in autistic individuals (see Pharmacogenomics, below). o Brain Mechanisms: Studies of brain mechanisms underlying the development, regulation, and modulation of behaviors characterizing autism and autism spectrum disorders, particularly those mechanisms involving communication and social interaction; studies of brain mechanisms and biological factors underlying autistic regression, or the loss of previously acquired skills; studies of brain mechanisms involved in the development of abnormal electroencephalograms and epilepsy and studies to clarify the subtypes of seizures and seizure disorders in autism; studies to define the neurobiological basis of neurological abnormalities and neuropsychiatric symptoms, including motor stereotypies, gait abnormalities, akinesias, dyskinesias, obsessive/compulsive traits, and the exacerbation of these symptoms, including the role of neuroimmune/autoimmune factors; studies that seek to define basic processing deficits using neuropsychological and cognitive neuroscience techniques; studies to develop animal models of brain dysfunction in autism and autism spectrum disorders, based on either genetic or environmental factors or their interaction. o Cognitive Science: Developmental studies of relevant behaviors during infancy including attention to social and nonsocial stimuli, affective behavior, gaze, vocalization, imitation, initiative, reciprocity, attachment, play, compliance, and self-recognition and their emergence in children with autism and autistic spectrum disorders; research on the delays and deviations in social behavior and cognition during preschool and middle school, including empathy, receptive social cognitive deficits (i.e., difficulties understanding others), and expressive difficulties; studies leading to more sophisticated tests of higher cognitive functioning, especially in social, communicative, reasoning, and problem-solving areas, as well as tests of basic attentional, emotional and cognitive deficits that may underlie these deficits or be precursors to them; studies of theory of mind, of unconventional verbal behaviors, and of the sensory-motor factors involved in relevant social cognition; and the development, validation, and refinement of interventions designed to address deficits in complex social and cognitive abilities or their developmental precursors; interventions designed to lessen or remediate cognitive deficits. o Communication Skills: Longitudinal, developmental studies of behaviors that are precursors to later communication and their emergence in children with autism and autistic spectrum disorders; sensory, motor, and social-cognitive impairments that impact upon interaction and communication; predictors of loss of or regression in expressive language abilities; interventions designed to remediate communication and related deficits across the life-span. o Pharmacological/Biological Interventions: Studies aimed at developing and testing the efficacy and safety of pharmacological agents that specifically target the core features of autism and autistic spectrum disorders; studies of the efficacy and safety of pharmacological and combined treatments for the most common and impairing psychopathology associated with autism (e.g., hyperactivity, impulsivity, aggression, self-injury, and obsessive-compulsive symptoms); studies that relate characteristics of individuals (or diagnostic subtypes) to therapeutic response and treatment outcomes (also see Pharmacogenomics , below); new approaches to treatment that build on advances in neuroscience, genetics, immunology, and other neurobiologic fields; focused interventions that test specific theories or hypotheses regarding possible neuropathogenesis; studies that address the benefits of combined drug and cognitive, behavioral, or psychosocial interventions; development of innovative methodologies and outcome measures. o Pharmacogenomic Studies: construction and analysis of SNP haplotypes that predict therapeutic response or adverse reactions to drugs; correlation of drug response profiles with intermediate phenotypes (e.g., brain imaging, neurophysiology, learning and memory, sustained attention); identification of biomarkers to resolve clinical heterogeneity and heterogeneity of therapeutic drug response; application of high-throughput approaches to screen for drug candidates metabolized by or inhibitors of polymorphic drug-metabolizing enzymes, e.g., CYP2D6; studies of genetically determined functional changes in nuclear and cell surface receptors to explain the ineffectiveness of therapeutic agents and adverse or paradoxical drug responses; studies of allelic variation occurring in individual transporter genes that are associated with a functional consequence. o Psychosocial Interventions: Studies developing new treatments (e.g., behavioral, cognitive-behavioral) and studies validating, refining, and comparing approaches to the treatment of persons with autism and autism spectrum disorders and their families, as well as studies that analyze and define the critical features of effective intervention; studies that relate characteristics of individuals (or diagnostic subtypes) to treatment outcomes; research on relevant contextual factors including physical and community environments, parent-child and sibling-child relationship factors, and peer-child interactions; studies addressing generalization or the transfer of learning from one setting to another; studies that develop and test interventions for infants and toddlers with confirmed or suspected autism spectrum disorders; studies that develop and test interventions to outcome in school and community settings throughout the lifespan; development of innovative methodologies and outcome measures. o Services Research: research on the organization, delivery, coordination, and financing of services for persons with autism spectrum disorders, and their families, within or across service settings; studies aimed at better identifying and addressing changes in service and rehabilitative needs across the life-span, including during transitions from childhood to adolescence, and adolescence to adulthood; interventions to improve the quality and outcomes of treatment and rehabilitation services; studies to develop improved measures of adaptive capabilities for children, adolescents, and adults with autism spectrum disorders; studies of ways to coordinate or integrate services across settings including specialty mental health, general health, and other settings such as educational, vocational, and housing services, in order to maximize receipt of appropriate services; and research on the economic factors effecting the delivery of needed services and treatments including cost-benefit, cost-effectiveness, and cost utility analyses of service interventions. MECHANISMS OF SUPPORT This PA will use the NIH research project grant (R01), small grant (R03), and exploratory/developmental grant (R21) award mechanisms. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project. Competing supplements to existing studies can also be used. The Small Grant (R03) provides 2 years of funding with a maximum of $50,000 direct costs for each year. Instructions for the R03 application can be found at ( Applicants considering use of this mechanism for an application to NINDS should contact NINDS staff (below) for information about specific restrictions. The Exploratory/Developmental Grant (R21) provides 2 years of funding with a maximum of $275,000 direct costs over the entire budget period; with no 1 year exceeding $200,000. Instructions for the R21 application may be found at: Applicants considering use of this mechanism for an application to NINDS should contact NINDS staff (below) for information about specific restrictions. This PA uses just-in-time concepts. It also uses the modular budgeting as well as the non-modular budgeting formats (see Specifically, if you are submitting an application with direct costs in each year of $250,000 or less, use the modular budget format. Otherwise follow the instructions for non-modular budget research grant applications. This program does not require cost sharing as defined in the current NIH Grants Policy Statement at Investigators might also want to consider relevant Institute-specific mechanisms, including the NIMH collaborative R01 mechanism Collaborative R01s for Clinical and Services Studies of Mental Disorders and Aids, PA-01-123, which is located at; the NIMH R34 mechanism for exploratory interventions and services research grants From Intervention Development to Services: Exploratory Research Grants , PAR-03-078, which is located at and the NIH R34 mechanism, which is available at ELIGIBLE INSTITUTIONS You may submit (an) application(s) if your institution has any of the following characteristics o For-profit or non-profit organizations o Public or private institutions, such as universities, colleges, hospitals, and laboratories o Units of State and local governments o Eligible agencies of the Federal government o Domestic or foreign institutions/organizations o Faith-based or community-based organizations INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs. SPECIAL REQUIREMENTS Dissemination of Data, Biomaterials for Genetic Studies Applications for genetic studies must include a data sharing plan. Data and biomaterials from subjects included in genetic projects funded under this PA will be made available and distributed to the broader scientific community, in accordance with existing procedures and protocols for the NIMH Human Genetics Initiative. Pharmacogenomic studies are expected to make data available for inclusion in PharmGKB (, an NIH-supported knowledge base for pharmacogenetic information (see below). It is expected that the information to be shared includes all genetic, clinical and diagnostic information, in addition to cell lines and DNA. It is preferable that data and materials generated in genetics projects funded under this PA should be placed in common, public cell repositories and databases that are widely accessible by investigators in the scientific community. An NIMH-supported data management facility and cell repository - the NIMH Center for Collaborative Genetic Studies on Mental Disorders ( - is such a community resource. Further information is available from the NIMH program staff contact listed below. It is expected that the investigator’s data sharing plan will specify the following elements: (1) the creation of comprehensive and verified databases that contain all clinical, diagnostic, and genetic information collected and produced in the project; (2) the establishment of high-quality cell lines, from which DNA will be extracted and stored, for all subjects studied from whom blood samples have been obtained; (3) mechanisms by which all databases and biomaterials (DNA samples, cell lines) are widely distributed to qualified investigators in the scientific community; (4) a protocol for wide dissemination of these data and biomaterials; (5) a timetable for distribution; and (6) an assurance that data and biomaterials are disseminated in a manner comparable to pre-existing protocols and procedures for distributing such data and biomaterials in the NIMH Human Genetics Initiative (see NIMH, in consultation with NIH’s Office of the General Counsel, the National Human Genome Research Institute's Ethical, Legal, and Social Implications Research Program and the Department of Health and Human Services' Office for Human Research Protections, has developed a model consent form for use in human genetic research at Consent forms for pharmacogenomic studies should also include explicit disclosure that de- identified data will be posted to PharmGKB. WHERE TO SEND INQUIRIES We encourage your inquiries concerning this PA and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into two areas: scientific/research and financial or grants management issues: o Direct your questions about scientific/research issues to: Ann Wagner, Ph.D. National Institute of Mental Health 6100 Executive Boulevard, Room 7149, MSC 9633 Bethesda, MD 20857-9633 Telephone: (301) 443-4283 FAX: (301) 443-4045 Email: Judith Cooper, Ph.D. National Institute on Deafness and Other Communication Disorders Executive Plaza South, Room 400C-11 - MSC 7180 Bethesda, MD 20892-7180 Telephone: (301) 496-5061 FAX: (301) 402-6251 Email: Alice Kau, Ph.D. National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 4B09F, MSC 7510 Bethesda, MD 20892-7510 Telephone: (301) 496-1383 FAX: (301) 496-3791 Email: Deborah Hirtz, M.D. National Institute of Neurological Disorders and Stroke 6001 Executive Boulevard, Room 2212, MSC 9250 Bethesda, MD 20892-9250 Telephone: (301) 496-5821 FAX: (301) 480-1080 Email: Cindy P. Lawler, Ph.D. National Institute of Environmental Health Sciences P.O. Box 12233, MD EC-23 Research Triangle Park, NC 27709 Telephone: (919) 316-4671 FAX: (919) 541-5064 Email: Kathy Mann Koepke, Ph.D. National Institute of Nursing Research 6701 Democracy Boulevard, Suite 7101, MSC 4870 Bethesda, MD 20892-4870 Telephone: (301496-9623 FAX: (301) 480-8260 Email: o Direct your questions about financial or grants management matters to: Rebecca Claycamp, CRA Chief Grants Management Officer National Institute of Mental Health 6001 Executive Boulevard, Room 6122, MSC 9605 Bethesda, MD 20892-9605 Telephone: (301) 443-2811 FAX: (301) 443-6885 Email: Christopher Robey Grants Management Team Leader National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8A17K - MSC 7510 Bethesda, MD 20892-7510 Telephone: (301) 435-6996 FAX: (301) 480-4783 Email: Sara Stone Chief, Grants Management Branch National Institute on Deafness and Other Communication Disorders 6120 Executive Boulevard, EPS-400-B MSC-7180 Bethesda, MD 20892-7180 Telephone: (301) 402-0909 FAX: (301) 402-1758 Email: Rita V. Sisco Grants Management Branch National Institute of Neurological Disorders and Stroke 6001 Executive Boulevard, Room 3265, MSC 9537 Rockville, MD 20852-9537 Telephone: (301) 496-7488 FAX: (301) 402-0219 Email: Lerlita Garcia Grants Management Branch National Institute of Environmental Health Sciences P.O. Box 12233, MD EC-22 Research Triangle Park, NC 27709 Telephone: (919) 316-4638 FAX: (919) 541-2860 Email: Diane E. Drew Office of Grants and Contracts Management National Institute of Nursing Research 6701 Democracy Boulevard, Suite 7101, MSC 4870 Bethesda, MD 20892-4870 Telephone: (301) 594-2807 FAX: (301) 451-5651 Email: SUBMITTING AN APPLICATION Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001). Applications must have a Dun and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for Federal grants or cooperative agreements. The DUNS number can be obtained by calling (866) 705-5711 or through the web site at The DUNS number should be entered on line 11 of the face page of the PHS 398 form. The PHS 398 is available at in an interactive format. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: The title and number of this program announcement must be typed on line 2 of the face page of the application form and the YES box must be checked. APPLICATION RECEIPT DATES: Applications submitted in response to this program announcement will be accepted at the standard application deadlines, which are available at Application deadlines are also indicated in the PHS 398 application kit. SPECIFIC INSTRUCTIONS FOR MODULAR BUDGET GRANT APPLICATIONS: Applications requesting up to $250,000 per year in direct costs must be submitted in a modular budget grant format. The modular budget grant format simplifies the preparation of the budget in these applications by limiting the level of budgetary detail. Applicants request direct costs in $25,000 modules. Section C of the research grant application instructions for the PHS 398 (rev. 5/2001) at includes step-by-step guidance for preparing modular grants. Additional information on modular grants is available at SPECIFIC INSTRUCTIONS FOR APPLICATIONS REQUESTING $500,000 OR MORE PER YEAR: Applications requesting $500,000 or more in direct costs for any year must include a cover letter identifying the NIH staff member within one of NIH institutes or centers who has agreed to accept assignment of the application. Applicants requesting more than $500,000 must carry out the following steps: 1) Contact the IC program staff at least 6 weeks before submitting the application, i.e., as you are developing plans for the study; 2) Obtain agreement from the IC staff that the IC will accept your application for consideration for award; and, 3) Identify, in a cover letter sent with the application, the staff member and IC who agreed to accept assignment of the application. This policy applies to all investigator-initiated new (type 1), competing continuation (type 2), competing supplement, or any amended or revised version of these grant application types. Additional information on this policy is available in the NIH Guide for Grants and Contracts, October 19, 2001 at SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of the application, including the checklist, and five signed photocopies in one package to: Center for Scientific Review National Institutes of Health 6701 Rockledge Drive, Room 1040, MSC 7710 Bethesda, MD 20892-7710 Bethesda, MD 20817 (for express/courier service) APPLICATION PROCESSING: Applications must be mailed on or before the receipt dates described at The CSR will not accept any application in response to this PA that is essentially the same as one currently pending initial review unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an unfunded version of an application already reviewed, but such application must include an Introduction addressing the previous critique. Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within 8 weeks. PEER REVIEW PROCESS Applications submitted for this PA will be assigned on the basis of established PHS referral guidelines. Appropriate scientific review groups convened in accordance with the standard NIH peer review procedures ( will evaluate applications for scientific and technical merit. As part of the initial merit review, all applications will: o Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score o Receive a written critique o Receive a second level review by the appropriate national advisory council or board REVIEW CRITERIA The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to evaluate application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. The scientific review group will address and consider each of the following criteria in assigning the application’s overall score, weighting them as appropriate for each application. o Significance o Approach o Innovation o Investigator o Environment The application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward. SIGNIFICANCE: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? APPROACH: Are the conceptual framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? INNOVATION: Does the project employ novel concepts, approaches or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? INVESTIGATOR: Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? ENVIRONMENT: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed. (See criteria included in the section on Federal Citations, below). INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated. (See Inclusion Criteria in the sections on Federal Citations, below). CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to be used in the project, the five items described under Section f of the PHS 398 research grant application instructions (rev. 5/2001) will be assessed. ADDITIONAL REVIEW CONSIDERATIONS SHARING RESEARCH DATA: Applicants requesting more than $500,000 in direct costs in any year of the proposed research are expected to include a data sharing plan in their application. The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or priority score BUDGET: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. AWARD CRITERIA Applications submitted in response to a PA will compete for available funds with all other recommended applications. The following will be considered in making funding decisions: o Scientific merit of the proposed project as determined by peer review o Availability of funds o Relevance to program priorities REQUIRED FEDERAL CITATIONS HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained. DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for all types of clinical trials, including physiologic, toxicity, and dose-finding studies (phase I); efficacy studies (phase II), efficacy, effectiveness and comparative trials (phase III). The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risk to the participants. (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: SHARING RESEARCH DATA: Starting with the October 1, 2003 receipt date, investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible Investigators should seek guidance from their institutions, on issues related to institutional policies, local IRB rules, as well as local, state and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score. INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research - Amended, October, 2001," published in the NIH Guide for Grants and Contracts on October 9, 2001 (; a complete copy of the updated Guidelines are available at The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH- defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. This policy applies to all initial (Type 1) applications submitted for receipt dates after October 1, 1998. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects that is available at REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH policy requires education on the protection of human subject participants for all investigators submitting NIH proposals for research involving human subjects. You will find this policy announcement in the NIH Guide for Grants and Contracts Announcement, dated June 5, 2000, at HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on hESCs can be found at and at Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (see It is the responsibility of the applicant to provide, in the project description and elsewhere in the application as appropriate, the official NIH identifier(s)for the hESC line(s)to be used in the proposed research. Applications that do not provide this information will be returned without review. PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at Applicants may wish to place data collected under this PA in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award. STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION: The Department of Health and Human Services (DHHS) issued final modification to the Standards for Privacy of Individually Identifiable Health Information , the Privacy Rule, on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR). Those who must comply with the Privacy Rule (classified under the Rule as covered entities ) must do so by April 14, 2003 (with the exception of small health plans which have an extra year to comply). Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website ( provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on Am I a covered entity? Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site. HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS- led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at 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 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284 and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

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