Part I Overview Information


Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH) ( www.nih.gov)

Components of Participating Organizations
National Institute of Mental Health (NIMH) (http://www.nimh.nih.gov)

Title: Center for Genomic and Phenomic Studies in Autism (U24)

Announcement Type
New

Request For Applications (RFA) Number: RFA-MH-07-080

Catalog of Federal Domestic Assistance Number(s)
93.242

Key Dates
Release Date:  November 29, 2006
Letters of Intent Receipt Date(s): December 27, 2006
Application Receipt Date(s): January 26, 2007
Peer Review Date(s): February/March 2007
Council Review Date(s): May 2007
Earliest Anticipated Start Date: July 1, 2007
Additional Information To Be Available Date (URL Activation Date): 
Expiration Date: January 27, 2007

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Table of Contents


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
  1. Research Objectives

Section II. Award Information
  1. Mechanism(s) of Support
  2. Funds Available

Section III. Eligibility Information
  1. Eligible Applicants
    A. Eligible Institutions
    B. Eligible Individuals
  2.Cost Sharing or Matching
  3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
  1. Address to Request Application Information
  2. Content and Form of Application Submission
  3. Submission Dates and Times
    A. Receipt and Review and Anticipated Start Dates
      1. Letter of Intent
    B. Sending an Application to the NIH
    C. Application Processing
  4. Intergovernmental Review
  5. Funding Restrictions
  6. Other Submission Requirements

Section V. Application Review Information
  1. Criteria
  2. Review and Selection Process
    A. Additional Review Criteria
    B. Additional Review Considerations
    C. Sharing Research Data
    D. Sharing Research Resources
  3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
  1. Award Notices
  2. Administrative and National Policy Requirements
    A. Cooperative Agreement Terms and Conditions of Award
       1. Principal Investigator Rights and Responsibilities
       2. NIH Responsibilities
       3. Collaborative Responsibilities
       4. Arbitration Process
  3. Reporting

Section VII. Agency Contact(s)
  1. Scientific/Research Contact(s)
  2. Peer Review Contact(s)
  3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


1. Research Objectives

Autism is a neurodevelopmental disorder with early childhood onset and characterized by significant impairments in social, communicative, cognitive and behavioral functioning. Symptoms persist throughout life, disrupt families and lead to significant disability. It is known that genes play a greater role in the risk of autism than in any other common neurodevelopmental disorder, with a reported monozygotic-twin concordance:dyzygotic-twin concordance ratio of ~25 and heritability > 90%. However, while genes exert a strong influence in aggregate, it is clear that autism is genetically complex, i.e., multiple genes of relatively small effect must interact to produce risk in combination with nongenetic factors. In addition, a more comprehensive understanding of autism’s etiology ultimately will require advanced knowledge of brain structure and function at multiple levels of analysis.

Understanding the genetic etiology behind a complex, multi-gene disorder like autism remains an important challenge. Methodologic and technical advances in molecular, cellular and genomic neuroscience are setting the stage for a new era in autism research, and will greatly facilitate the translation of findings from basic to clinical research paradigms that aim to identify targets for new therapeutics. Highly accurate and comprehensive phenotypic assessment is critical to the success of these endeavors, and will permit resolution of underlying etiologic heterogeneity, delineation of discrete clinical subtypes and identification of specific components of the disorder that differentially respond to pharmacologic and other therapies.

Comprehensive phenotypic characterization will accelerate identification of intermediate phenotypes – so-called endophenotypes – that index physiological processes that lie between the level of the genotype and phenotype. Potential endophenotypes in autism may index underlying brain structure/function and neurodevelopmental abnormalities include assessments of facial dysmorphology, cognitive and intellectual deficits, language and communication abnormalities and social deficits. To the extent that such traits are under genetic control, it is expected that they will aggregate in families. The analysis of endophenotypes in clinically unaffected relatives of autistic probands thus offers a powerful study design to study these traits independent of the confounding effects of treatment and disease progressions. Ultimately, robust assessments of this endophenotypes are expected to serve as biomarkers (changes in gene or protein expression in relevant tissues , as determined from laboratory- and non-laboratory based approaches, e.g., brain imaging, biochemical assays) to resolve clinical heterogeneity and heterogeneity of therapeutic drug response. Such phenotypic assessments will play a potentially invaluable role in future clinical trials in autism, given their potential for identifying a new class of behavioral markers and clinical endpoints by which therapeutic efficacy may be assessed. Ultimately, the careful cataloging of clinical and endophenotypic features will be a prerequisite for the era of genomic medicine, in which detailed genetic information is utilized to develop individualized therapeutic regimens.

The key to the development of major translational paradigms in autism – by which underlying genetic and other biological information are indexed by endophenotypic or clinical measures – will be robust, rapid and comprehensive assessment of the autism phenotype.  “Phenomics” is the name given to the science which attempts to integrate the information provided by all these areas of study into a holistic picture of the complete organism – its phenotype.

Environmental factors are clearly of importance in the etiology of autism. Ongoing work is focused on identifying specific components of environmental risk, and the methodologies that are most suitable for making such assessments. For example, several researchers are now beginning to explore the links between environmental chemicals that may alter brain function and regional brain growth. In the interim, it is expected that the Center will collect information that will inform future studies of the environment on brain development in autism and the effect of selected environmental agents, beginning with neuron formation and growth and proceeding to the overall behavior of the organism.  Identification of environmental exposure and diagnostic biomarkers will allow researchers to measure exposure or susceptibility in children with autism more systematically.  Examples of specific Center activities include the following: administration to parents or caregivers of a comprehensive environmental exposure assessment; collection of blood plasma, urine, and saliva; identification of signature profiles of metabolites and analytes; identification of metabolomic and proteomic signatures in subgroups of autistic patients; and the development of appropriate biomarker panels to measure proteins and metabolites

In order to develop a comprehensive catalog of the autism phenotype, the National Institute of Mental Health (NIMH) and its funding partners are soliciting applications that will establish a Center for Genomic and Phenomic Studies in Autism. The Center will accelerate identification and efficient measurement of a wide range of phenotypes across multiple behavioral, cognitive and social domains to advance interdisciplinary research on autism genomics and therapeutics. Facialdysmorphologies and cognitive, communication, behavioral and social abnormalities identified in autism offer quantitative phenotypes for genomic studies and clinical trials, and provide strong endophenotypic bridges to underlying neural systems models. The Center is expected to comprehensively collect in a high-throughput and highly reliable manner a set of phenotypic data from over 1500 autistic patients and their relatives from multiplex families collected nationwide for use in future studies. The data collected by the Center will be utilized to iteratively refine clinical phenotypes in interdisciplinary research and to provide translational validation of underlying physiological endophenotypes. A specific interest of this program is to collect an ethnically diverse sample of autistic probands and their relatives.The Center will require scientific expertise in the following areas:

The long-term goal of the Center is to foster trans-disciplinary research that will overcome bottlenecks in the discovery of treatments for autism that are caused by the use of traditional behavioral "symptom" phenotypes, which are heterogeneous and overlapping, and difficult to translate to basic research.

A specific goal of the Center will be to collect data and biomaterials for utilization in the next rounds of interdisciplinary genomic and basic and translational neuroscience research, including clinical trials. Autism phenotypes will be iteratively refined based on these data, in order to provide translational validation of physiological and other endophenotypes. The Center will initially leverage available resources such as provided by an NIH-funded hospital-based General Clinical Research Center (GCRC; http://www.gcrconline.org/) or a similar resource to provide bridging infrastructure and expertise in efficient clinical screening and systematic nationwide recruitment (especially in regard to ethnically diverse populations), database management, bioinformatics, high-throughput diagnostic assessments (of cognitive and intellectual functioning, language and communication skills, social functioning and adaptive functioning), quantitative dysmorphology utilizing state-of-the-art 3D morphometry and scanning of the craniofacial surface, cytogenetic analysis, clinical trials and regulatory issues, bioethics and human consent issues, and rapid data sharing. Specific functions and services to be performed by the Center include:

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

Section II. Award Information


1. Mechanism(s) of Support

This RFA is a one-time solicitation. This RFA will use the NIH Resource-Related Research Projects – Cooperative Agreements award mechanism (U24). In the cooperative agreement mechanism, the Principal Investigator retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".

This funding opportunity uses the just-in-time budget concepts. It also uses the non-modular budget format described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). A detailed categorical budget for the "Initial Budget Period" and the "Entire Proposed Period of Support" is to be submitted with the application.

2. Funds Available

NIMH intends to commit approximately $1,500,000 dollars in FY 2007 to fund one new cooperative agreement in response to this RFA. An applicant may request a project period of up to 5 years and a direct cost budget up to $1,250,000 in the first project year. Although the financial plans of the IC(s) and other sponsors provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficiently meritorious application.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

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

1.B. Eligible Individuals

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 support.

2. Cost Sharing or Matching

Cost sharing is not required.

3. Other-Special Eligibility Criteria

Not applicable.

Section IV. Application and Submission Information


1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance 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

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

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

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates
Letter of Intent Receipt Date: December 27, 2006
Application Receipt Date(s): January 26, 2007
Peer Review Date: February/March 2007
Council Review Date: May/June 2007
Earliest Anticipated Start Date: July 1, 2007

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed at the beginning of this document. The letter of intent should be sent to:

Thomas Lehner, Ph.D.

Division of Neuroscience & Basic Behavioral Science

National Institute of Mental Health

6100 Executive Blvd., Room 7190, MSC 9643
Bethesda, MD 20892-9643
Telephone: (301) 443-1706
FAX: (301) 402-4740
Email: tlehner@mail.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the research grant applications found in the PHS 398 instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three 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 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Jean Noronha, Ph.D.
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6154, MSC 9609
Bethesda, MD 20892-9609
Telephone: (301) 443-3367
FAX: (301) 443-4720
Email: jnoronha@mail.nih.gov

Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf.

3.C. Application Processing

Applications must be received on or before the application receipt date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by NIMH. Incomplete and non-responsive applications will not be reviewed. If the application is not responsive to the RFA, NIH staff may contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next appropriate NIH review cycle.

The NIH will not accept any application in response to this funding opportunity 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.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

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 competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must 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 competing continuation 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 must 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 NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.

6. Other Submission Requirements

The GPSC will meet twice a year at NIMH.  Applications in response to this RFA should include a request for funds to cover the expense of attending these meetings in Rockville, MD.

Plan for Sharing Research Data

The NIH data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing.  All applications submitted in response to this RFA must include a plan for sharing research data. The precise content of each data-sharing plan will vary, depending on the data being collected and the expected schedule for data sharing. References to data sharing may also be appropriate in other sections of the application.  

The reasonableness of the data sharing plan will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting

Data Sharing in the Center for Genomic and Phenomic Studies in Autism

The sharing in a timely manner of biomaterials and data has been an essential element in the rapid progress that has been made in the genetic analysis of human diseases. To address the joint interests of the government in the availability of, and access to, the results of publicly funded research and in the opportunity for economic development based on these results, NIH requires applicants who respond to this RFA to develop and propose detailed plans for data sharing. It is expected that data sharing plans minimally include all phenotypic, endophenotypic and genotypic data. All data and biomaterials from subjects collected and studied by the Center are required to be placed for distribution in common, public cell repositories and databases that are widely accessible by investigators in the national and international scientific community. Data and biomaterials (DNA, cell lines) are required to be deposited in an NIMH-supported data management facility and cell repository – the NIMH Center for Collaborative Genetic Studies on Mental Disorders (http://nimhgenetics.org). Data also are required to be deposited in NDAR (http://ndar.nih.gov/index.asp), which currently is under development. Data from this database will be made available to other researchers, under the guidelines to be established by this entity, adhering to HIPAA and Human Subjects research codes.  

It is expected that the investigator's data sharing plan will include the following elements: (1) comprehensive and verified databases that contain all clinical, diagnostic, and genotypic information; (2) high-quality cell lines, from which DNA will be extracted and stored; (3) mechanisms by which all databases and any biomaterials (DNA samples and cell lines, if applicable) are widely distributed to qualified investigators in the scientific community; (4) a protocol for wide dissemination of these data and applicable biomaterials; (5) a timetable for distribution; and (6) an assurance that data and applicable biomaterials are disseminated in a manner comparable to pre-existing protocols and procedures for distributing such data and biomaterials in the NIMH Human Genetics Initiative (see http://nimhgenetics.org).

The timeline for data sharing is evolving, and expectations for rapid data sharing are increasing. It is expected that all data will be released to the scientific community no later than one year after they are generated and validated. More rapid sharing, i.e., at quarterly intervals during the award period, is strongly encouraged.

NIMH, in consultation with NIH's Office of the General Counsel, the National Human Genome Research Institute's Ethical, Legal, and Social Implications Research Program and the Department of Health and Human Services' Office for Human Research Protections, has developed a model consent form for use in human genetic research at http://zork.wustl.edu/nimh/NIMH_initiative/NIMH_initiative_link.html. This may then serve as a template that is subject to modification and/or approval by local institutional review boards. NIMH will review consent forms and IRB approvals for all projects prior to funding under this RFA. It is expected that the applicant's approved consent form address the following:

The adequacy of the data sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

Section V. Application Review Information


1. Criteria

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

The following will be considered in making funding decisions:

2. Review and Selection Process

Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIMH in accordance with the review criteria stated below.

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

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an 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 or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Will the data to be shared by the applicant accelerate gene discovery, translational research and the development of new therapeutic compounds in autism?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?  Does the applicant utilize state-of-the-art diagnostic and clinical assessments, including high-throughput phenomics, quantitative dysmorphology and karyotyping? Does the applicant utilize an approach to screening and recruitment that will lead to the successful collection of an ethnically diverse sample of autistic probands and their relatives?

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for high-throughput phenomics and other Center activities?

Investigators: Are the investigators 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? Does the investigative team bring complementary and integrated expertise to the project (if applicable)? Does the investigative team have an established relationship with nationwide family recruitment efforts in autism? Does the investigative team have experience in diagnosis and high-throughput phenomics in autism?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support? Does the scientific environment include research infrastructure provided by an NIH-funded General Clinical Research Center (GCRC; http://www.gcrconline.org/)?

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

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 the Research Plan, Section E on Human Subjects in the PHS Form 398).

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 the Research Plan, Section E on Human Subjects in the PHS Form 398).

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

2.C. Sharing Research Data

Data Sharing Plan: 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 the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.  

2.D. Sharing Research Resources

NIH policy expects that grant award recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps/part_ii_5.htm#availofrr and http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

3. Anticipated Announcement and Award Dates

N/A.

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 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 (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

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 (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

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 Also Section IV.5. Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement (U24 - Resource-Related Research Project), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined above. Coordination of the Center's activities will be accomplished through close collaboration between the Center scientific staff, NIMH program staff, and a scientific steering committee (Genomic and Phenomic Steering Committee (GPSC)).  A Genomic and Phenomic Advisory Panel (GPAP), composed of experts not affiliated with the Centers or GPSC, also will be formed to provide scientific oversight of the Center. GPSC, GPAP, PI, and NIH responsibilities are described below.

2.A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for coordinating project activities scientifically

and administratively at the awardee institution, and will have primary responsibility for performing all scientific and fee-for-service activities. The awardee institution will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current NIH policies. The Center PI must agree to participate with NIMH program staff and GPSC in coordinating the activities of the Center. Specifically, the PI will:

2.A.2. NIH Responsibilities

An NIH (NIMH) “Project Scientist” will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. The NIMH Project Scientist will have substantial scientific/ programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination.  This includes functioning as a peer with the PIs, facilitating the partnership relationship between the NIMH and the Center, helping to maintain the overall scientific balance in the program commensurate with new research and emerging research opportunities, and ensuring that the activities of the Center are consistent with the scientific mission of the NIMH Human Genetics Initiative (http://zork.wustl.edu/nimh/NIMH_initiative/NIMH%20Human%20Genetics%20Initiative%20Mission.htm).  The role of the NIMH will be to facilitate and not to direct activities. The NIMH Project Scientist shall participate as a member of GPSC and will have one vote.  Specifically, the NIMH Project Scientist will:

Additionally, an agency program official (the NIMH project officer) will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. This will be a different individual than the NIMH Project Scientist.

2.A.3. Collaborative Responsibilities

Genomic and Phenomic Steering Committee (GPSC)

All collaborative activities of the awardee and NIMH staff will occur through the activities of GPSC, which will serve as the governing board of the Center. The NIMH will formally interact and collaborate with the Center through GPSC, which will include the PI, the NIMH Project Scientist, and two researchers (advisors) with relevant scientific expertise who are not affiliated with the Center. The GPSC Chair will be responsible for developing meeting agendas and chairing meetings.  GPSC will meet twice a year. Additional GPSC members may be added by action of NIH. NIH staff may attend GPSC meetings. The NIH Project Scientist, PI, and each advisor will have one vote each.  In cases where members do not agree, any member may ask the chairperson to solicit a vote. In order for a decision or course of action to be finalized by GPSC, a majority of the possible votes must be cast in favor of the decision or course of action. GPSC will coordinate the activities of the Center.  GPSC will discuss scientific progress, make recommendations regarding the enhancement of research resources and facilitation of free and open sharing. GPSC will address GPAP recommendations. The awardee will be required to accept and implement the common protocol and procedures approved by GPSC.

Genomic and Phenomic Advisory Panel (GPAP)

GPAP will meet at least once each year and will oversee Center activities to assure that the needs of the broader scientific community in conducting basic and translational research on autism using Center resources are being met. GPAP will provide scientific advice to GPSC and NIMH. GPAP members will provide scientific and operational recommendations concerning both long-term developments and activities at the Center. GPAP also will consult on the incorporation of emerging high-throughput phenomic methodologies and technologies into Center activities. GPAP will consist of about 10 scientists (panelists) who are not affiliated with the Center. GPAP panelists will be appointed by the NIMH project officer and will be selected for their broad expertise in relevant topics such as diagnosis, cognitive assessment, dysmorphology, cytogenetics, high-throughput phenomics, molecular genetics, genomics, pharmacogenomics, statistical genetics, bioinformatics and translational neuroscience.  NIMH will select one panelist to be GPAP's chair.  Additional GPAP members may be added by an action of GPAP. The NIH Project Scientist will attend GPAP meetings as a non-voting member and will act as a representative of GPSC. Other NIH staff and GPSC members may attend GPAP meetings. GPAP panelists will not vote on GPSC but may be invited to attend GPSC meetings. Periodically, at intervals determined by GPSC, a formal request for advice on specific subjects will be submitted to GPAP. GPAP will convene to consider and formulate opinions on the questions submitted to it.  NIMH program staff will consider GPAP opinions with regard to overall Center functioning and when making determinations for renewal funding.

2.A.4. Arbitration Process

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the GPSC chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.

Section VII. Agency Contacts


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

1. Scientific/Research Contacts:

Thomas Lehner, Ph.D.
Division of Neuroscience & Basic Behavioral Science
National Institute of Mental Health
6100 Executive Blvd., Room 7190, MSC 9643
Bethesda, MD 20892-9643
Telephone: (301) 443-1706
FAX: (301) 402-4740
Email: tlehner@mail.nih.gov

2. Peer Review Contacts:

Jean Noronha, Ph.D.
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6154, MSC 9609
Bethesda, MD 20892-9609
Telephone: (301) 443-3367
FAX: (301) 443-4720
Email: jnoronha@mail.nih.gov

3. Financial or Grants Management Contacts:

Dawn Walker
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6115, MSC 9605
Bethesda, MD 20892-9605
Telephone: (301) 443-3858
FAX: (301) 443-6885
Email: walkerde2@mail.nih.gov

Section VIII. Other Information


Required Federal Citations

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

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). 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, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an application in response to this RFA are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and 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.

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 access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this 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 other human subjects procedures given the potential for wider use of data collected under this award.

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

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, 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 research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

For more information about the Policy or the submission process please visit the NIH Public Access Policy Web site at http://publicaccess.nih.gov/ and view the Policy or other Resources and Tools including the Authors' Manual (http://publicaccess.nih.gov/publicaccess_Manual.htm).

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).

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

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles.  Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

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

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

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

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related 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 research 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 applications 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 must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.


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NIH Funding Opportunities and Notices


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