Part I Overview Information


Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations
This FOA is developed as a part of the NIH-wide Genes and Environment Initiative (GEI).  All NIH Institutes and Centers participate in NIH-wide initiatives.  This FOA will be administered by NHLBI (http://www.nhlbi.nih.gov) on behalf of the NIH (http://www.nih.gov).

Title: Methods of Analysis of Gene-Environment Interactions in Complex Diseases: The Genes and Environment Initiative (R01)

Announcement Type
New

Request For Applications (RFA) Number: RFA-HL-07-010

Catalog of Federal Domestic Assistance Number(s)
93.837

Key Dates
Release Date: November 20, 2006
Letters of Intent Receipt Date(s): December 29, 2006
Application Receipt Date(s): January 29, 2007
Peer Review Date(s): June-July 2007
Council Review Date(s): August 2007
Earliest Anticipated Start Date: September 2007  
Additional Information To Be Available Date (Url Activation Date): N/A
Expiration Date: January 30, 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

Nature of the Research Opportunity

The purpose of this Funding Opportunity Announcement (FOA) is to bring together expertise in the fields of genetics, environmental health, epidemiology, biostatistics, and bioinformatics to develop and test innovative, informative, and cost-effective study designs and analytical strategies for identifying gene and environment interactions in genome-wide association (GWA), sequencing, linkage, or candidate gene studies in complex diseases. 

The Genes and Environment Initiative (GEI) is a four-year, NIH-wide program proposed in the President’s FY2007 budget and currently awaiting Congressional approval. If approved, the program will support efforts to identify major genetic susceptibility factors for diseases of substantial public health impact and to develop technologies for reliable and reproducible measurement of potentially causative environmental exposures. It is being developed and implemented by an NIH-wide GEI Coordinating Committee, administratively led by the National Human Genome Research Institute (NHGRI) and the National Institute of Environmental Health Sciences (NIEHS).

GEI is intended to be a multi-component program involving several related solicitations. A major component will support genome-wide association studies (GEI-GWA), either in an initial discovery phase (assaying single nucleotide polymorphisms, or SNPs, to capture at least 80% of human genomic variation), or in a replication phase (assaying a subset of the most strongly associated SNPs or other genetic variants in one or more additional groups of subjects), as well as methods development for GWA.   Other GEI genetics components under consideration for future solicitations include further replication and fine mapping studies, sequencing, functional studies, database development, and clinical translation.  As these latter activities depend on availability of robust findings from high-throughput GWA genotyping, the production and analysis of GWA data as well as gene-environment interaction analyses are the focus of the first genetic component of GEI.

Recognizing that chronic diseases are likely due to environmental and behavioral factors interacting with genetic predisposition, GEI also includes a substantial environmental component devoted to developing and field testing new technologies for assessing such exposures. The potential for applying these technologies (particularly those suitable for use on stored biospecimens) in population samples selected through GEI for genetic studies will also be examined. Other GEI exposure biology components under consideration include development of environmental sensors for measurement of toxins, dietary intake, and physical activity; the development of biological response indicators for a variety of environmental stressors including oxidative stress, epigenetics, and DNA damage; and psychosocial stressors. Psychosocial stressors include, but are not limited to, exposure to adverse environments and life experiences such as natural disasters (e.g., earthquakes and hurricanes), crowding or isolation, catastrophic/traumatic events (e.g., war, terrorism), loss of job, disease, family violence, deprivation, child abuse, adverse social environments or situations (e.g., being a chronic caregiver to an ailing family member), and detrimental parental behaviors. Broad biological pathways known to be perturbed by environmental stressors and disease are of greatest interest in the development of new exposure assessment tools.  These include inflammation, oxidative stress, DNA damage, mitochondrial perturbations, endocrine disruption, xenobiotic biotransformation, immune activation, and epigenetic regulation. Important classes of exposures include, but are not limited to: environmental tobacco smoke, alcohol and ethanol, air pollution and its components, mycotoxins, pesticides, herbicides and insecticides, and addictive substances. New sensing devices will address priority chemical and biological agents that have been shown to cause or are suspected to be causative factors for common human diseases such as respiratory disease, neurological disease, and cancer.  Priority exposure classes will include ozone, particulate matter and diesel exhaust, metals (e.g., arsenic, cadmium, mercury), volatile organic compounds (e.g., benzene), PBDEs, PAHs, as well as molds and allergens.  The value of the existing epidemiologic and genotyping data for investigation of gene-environment interactions will be increased substantially by the addition of novel and informative analytical strategies. To ensure that the maximal scientific benefit is derived from this significant public investment, the analytical strategies and tools developed through this FOA will be made rapidly and widely available for research use. 

Background

Much of the burden of health for the United States and developing societies is due to chronic complex diseases such as heart disease, hypertension, diabetes, cancer, asthma, Alzheimer’s disease, Parkinson’s disease, autism, and many mental health disorders.  A combination of variations in multiple genes and environmental factors in interconnected biological pathways or networks are thought to contribute to the susceptibility and progression of these common complex human diseases and the variation in treatment responses to these diseases.  An understanding of the interactions between multiple genetic and environmental factors will most likely more accurately predict disease risk and treatment response and help explain disease etiology than any single genetic or environmental factor for many of these complex, chronic human diseases.

As the technology for measuring genetic variants advances and the amount of data available increases, it is increasing apparent that a major barrier to further progress and success of genetic studies, especially those with a gene-environment interaction component, is determining an appropriate methodological strategy for analysis and interpretation of results.  Hence, as additional resources and data for linkage, candidate gene and genome-wide association studies emerge, approaches to use these resources in the most efficient way are warranted.

Although most common chronic diseases are the result of complex interactions between genes (G) and environmental (E) factors, most analytical approaches adopted for genetic linkage and association studies do not incorporate interactive effects with environmental factors.  Studies have indicated that failure to account for G x E interactions in complex disease association analyses can decrease the power to find genetic disease loci and underestimate both the genetic and environmental effects of the disease.  The potential for detecting genes could be enhanced by taking environmental agents that are already known to play a key role in the disease etiology into account, particularly if these interactions are already known (e.g, tobacco smoking is known environmental risk factor for lung or colorectal cancer).  In addition, the failure to replicate many genetic association studies is believed to be in part because of the failure to address gene-environment interactions into the study design.  The success of genetic studies, in general, to identify genetic variants for complex diseases will therefore be dependent on the further development of methods and analytical tools that can incorporate these complex interactions.  Identification of study designs and analytical methods that will enhance the possibility of detecting, characterizing, and interpreting gene-environment interactions will contribute to the success of the GEI initiative.   Additionally, innovative strategies and new tools are necessary to test multiple gene and environmental risk factors for complex diseases and incorporate gene-environments interactions into standard linkage analyses and candidate gene approaches.

Although traditional methods to assess exposure can accurately determine the concentration of a variety of toxins in the environment or in human biospecimens, these methods fall short of accurately determining the biological response to exposures. Evidence suggests that the biological response to the exposure, rather than simply the exposure, is more tightly related to the ultimate impact on human health. For the purposes of GEI, environmental exposure refers to chemical toxicants such as metals and solvents, and biological agents such as toxins released from mold and bacteria, that are contaminants of the natural environment of air, water, and soil. It also encompasses lifestyle factors such as diet and physical activity which contribute to and modulate the biological response to these environmental agents. Family, social and cultural influences that may modify the pathophysiologic responses to environmental exposures will be considered to the extent that they can be measured in biological assays. Additionally, for the purpose of this FOA, pharmacotherapy is considered an environmental exposure.  It is fully expected that the technological and analytical achievements supported by GEI will result in biological “fingerprints” of prior exposure to environmental agents and lifestyle choices, and the ability to interpret these associations. These improved exposure measures can be linked to genetic data to determine their relationships to genomic variants, as well as their potential for modifying the associations of these variants with disease.

Scientific Knowledge to be Achieved

The NIH-wide Genes and Environment Initiative (GEI) has the long-range goal of determining the etiology of common diseases by focusing on genetic and environmental factors that increase the risk of these diseases, and the interaction among these factors.  GEI will provide valuable scientific contributions to health disparities research by collecting and analyzing genotype, phenotype, and exposure data, while simultaneously measuring other factors within disease subgroups (e.g., race, ethnicity, behaviors, geography, genetic backgrounds, exposures and social environments) that may lead to differential health outcomes.

Objectives of this Research Program

This FOA for the Genes and Environment Initiative Gene-Environment Interaction Analysis (GEI-GXE Interaction Analysis) will focus on the development of analytical tools and approaches to identify environmental components or covariates of complex diseases and their interactions with genes in linkage, candidate gene, sequencing, or genome-wide association studies.  This FOA encourages the development and subsequent validation of algorithms and new computational approaches to help identify individuals at highest risk for developing a specific disease or dysfunction based on both their exposure patterns and genetic risk profiles.  Programmatic priority will be placed on methods that allow the integration of new exposure assessment tools as developed in the Exposure Biology GEI initiatives into whole genome association studies such as those developed from GEI-GWA. The identification of subsets of individuals with high disease risks due to particular combinations of genetic variants and environmental exposures or stressors will allow development of more targeted therapies, interventions, or preventative strategies, as well as maintenance of health.

Examples of general research questions and approaches that would be relevant under this FOA include, but are not limited to:

Program Organization

The GEI-GXE Interaction Analysis program is part of the larger GEI program, which will include additional initiatives in genetics and exposure biology.  The awards funded under all this FOA will be investigator-initiated research program grants (R01).  

Interaction with the other components of the GEI program, including the NIH, may be required. The awardees will meet as a group, which will include the Study Investigators, and NIH, twice per year to share information on methodologies, analytical tools, as well as data and preliminary results. Key co-investigators, and pre- and postdoctoral trainees, in addition to the PIs, are eligible to attend these meetings.  PIs are encouraged to include investigators and trainees who are members of under-represented minority groups and those from different but related disciplines such as computational biology, social sciences, public health, and translational research where appropriate.  The cost of 3-4 persons to attend these meetings should be included in the proposed research budget.  A plan to share all analytical methods and tools (e.g., software) with the scientific community is required.  Other data and publications should be made openly available through a public web site and publication in the scientific literature.

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

This FOA will not support the recruitment of human subjects, collection of human samples, collection of phenotype or medical data, or studies using animal models.  Investigators are expected to have a disease model that is useful for studying gene-environment interactions (i.e., a disease model with evidence of an environmental component or that can be explained by an environmental component).

Both real genotyping data and/or simulated data may be used to develop novel strategies for gene discovery and apply them to elucidate the genetics and environmental components of complex disease, in response to this FOA.  Investigators are expected to clearly define the collection and description of environmental and phenotype data.  If possible, applicants should provide solid evidence of ways to quantitate, measure, or assess the environmental component of the proposed studies utilized for methods development.

Section II. Award Information


1. Mechanism(s) of Support

This funding opportunity will use the investigator-initiated research program (R01) award mechanism(s).

As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses just-in-time concepts. It also uses the modular as well as the non-modular budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if you are submitting an application with direct costs in each year of $250,000 or less, use the modular budget format described in the PHS 398 application instructions. Otherwise follow the instructions for non-modular research grant applications.

2. Funds Available

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

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:

Investigators from the NIH Intramural Research Program (IRP) will also be eligible to participate in the NIH-wide Genes and Environment Initiative (GEI).  This will serve to expand the resources available to GEI, by encouraging significant participation of intramural investigators and staff whose salaries are already supported by the NIH.    NIH is seeking a broad range of studies for inclusion in GEI, and recognizes that potentially eligible and meritorious studies may be ongoing within the IRP.  Expanding this program to include IRP investigators will help GEI meet its goals of including the most highly scientifically meritorious projects, accessing diverse population samples, and ensuring programmatic balance across disease areas.  It will also assist in meeting goals for enhancing intramural-extramural collaborations as outlined in the 2003 Institute of Medicine Report, “Enhancing the Vitality of the National Institutes of Health.”  IRP investigators will not be directly competing for the R01 awards.  They will be submitting requests to compete for the provision of IRP funds, which have been allocated for GEI. Requests for the participation of the NIH IRP will be competitively reviewed.  

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.

The most current Grants Policy Statement can be found at: http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#matching_or_cost_sharing.

3. Other-Special Eligibility Criteria

An individual may only submit one application as the Principal Investigator.

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.

Foreign Organizations

Several special provisions apply to applications submitted by foreign organizations:

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.

NIH Intramural Research Program (IRP)

The requests from NIH intramural scientists will be submitted using the format of PHS 398 application kit (http://grants.nih.gov/grants/funding/phs398/phs398.html).  The NIH intramural scientist requests will be reviewed separately by the same peer review group.

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(s): December 29, 2006
Application Receipt Date(s): January 29, 2007
Peer Review Date(s): June-July 2007
Council Review Date(s): August 2007
Earliest Anticipated Start Date(s): September 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:

Chief, Review Branch
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Rockledge II, Room 7214, MSC 7924
Bethesda, MD 20892 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)  
Telephone: (301) 435-0270
FAX: (301) 480-0730
Email: NHLBIchiefreviewbranch@nhlbi.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:

Chief, Review Branch
Scientific Review Branch
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Room 7214, MSC 7924
Bethesda, MD 20892 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: (301) 435-0270
FAX: (301) 480-0730
Email:  NHLBIchiefreviewbranch@nhlbi.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 the NHLBI. Incomplete and non-responsive applications will not be reviewed.

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

Special Application Requirements

Applicants must address the following when preparing applications in response to this FOA.  Items A-D in the application (Specific Aims, Background and Significance, Preliminary Studies and Research Design and Methods) should not exceed 25 pages.

Applicants are expected to document access to existing DNA samples, environmental exposure and phenotypic data from existing human studies.  Applicants should describe all relevant phenotypic and environmental exposure measures from the study.  Additionally, applicants should provide strong justification for the choice of study design and methodological/analytical strategy proposed.

Applicants are expected to provide a plan to share analytical methods and tools with the scientific community in a timely manner, and should address any concerns regarding intellectual property.  Any application that does not include this information will be considered non-responsive.

Applications that include the recruitment of human subjects, collection of biological samples, and/or collection of phenotypic and other medical data will be considered non-responsive and returned to the applicant.

If selected, NIH intramural scientists will participate in GEI programs as Principal Investigators in accord with the Terms and Conditions of Award provided in this FOA.

Specific Instructions for Modular Grant Applications

Applications requesting up to $250,000 per year in direct costs must be submitted in a modular budget format. The modular budget 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 at http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step guidance for preparing modular budgets. Applicants must use the currently approved version of the PHS 398. Additional information on modular budgets is available at http://grants.nih.gov/grants/funding/modular/modular.htm.

Plan for Sharing Research Data

All applicants must include a plan for sharing research data.  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.

All participants in GEI-GXE Interaction Analysis are expected to promote the GEI-GXE Interaction Analysis policies of data access, publication, and intellectual property as summarized below, and describe their methods for doing so in the applications.  NIH will establish mechanisms to monitor agreement with these policies.

The NIH expects that all GEI-supported data and conclusions derived directly there from will remain freely available, without licensing requirements, for uses such as, but not limited to, methods and tools for identifying markers that can be used for new potential targets for drugs, therapeutics, and diagnostics.  The intent is to discourage the use of patents that would prevent use or block access to any methods or tools developed with GEI support.   The NIH encourages broad use of GEI-GXE Interaction Analysis methods and tools that are consistent with a responsible approach to management of intellectual property derived from downstream discoveries as outlined in NIH’s Best Practices for the Licensing of Genomic Inventions and the NIH Research Tools Policy (http://grants.nih.gov/grants/intell-property_64FR72090.pdf).

Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7, patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights. 

Sharing Research Resources

NIH policy expects that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

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.

As the Analysis component of the GEI is a community resource project, the NIH expects that the resources generated during the course of this program (e.g., analytic methods and tools) will be made rapidly available to the research community.  The applicant should provide specific plans for resource sharing and distribution in the application.  

Section V. Application Review Information


1. Criteria

The following will be considered in making funding decisions:

2. Review and Selection Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NHLBI 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? Does the application address a significant and genetically complex trait with an environmental component and demonstrate a need to develop a method or tool to address the analytical strategies for a genome-wide association study for this trait?   

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? Is the dataset appropriate for the work relevant to the goals of the FOA? Are the study design and population chosen appropriate for the aims proposed?    

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 this area? What advantages do the proposed methods and tools offer over those that currently exist?  What advantages do they offer for the investigation of new measures of environmental exposures and GWA studies developed by the GEI? 

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)?

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? Are the bioinformatics and IT infrastructures sufficient to accomplish the goals of the project?

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).

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

The NIH has identified the GWA Analysis component of GEI as a community resource project.  As such, the program aims to function openly by making all data (i.e., analysis methods and tools) available to the scientific community in a timely manner prior to publication, with suitable restrictions for protection of human research subjects.  The applicant should provide specific plans for data release in the application. 

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.

Program staff will be responsible for the administrative review of the plan for sharing data. The adequacy of the data 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 sharing plan with the awardee before recommending funding of an application. The final negotiated version of the data sharing plan will become a condition of the award. The effectiveness of the data sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

2.D. Sharing Research Resources

NIH policy expects that grant 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.

Reviewers will be asked to assess the adequacy of the resources sharing plan.  However, 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

Section VI. Award Administration Information


1. Award Notices

After the peer review of the application is completed, the Principal Investigator will also receive a written critique called a Summary Statement.

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).

3. Reporting

Awardees will be required to submit electronically quarterly reports that describe the data and resources that have been shared with the scientific community.  The quarterly report will be used as a management tool for the NIH determine the most efficient approaches to sharing methods and tools and to identify early any correctable problems. 

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:

Cashell E. Jaquish, Ph.D.
Program Director
Division of Prevention and Population Sciences
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Rockledge II, Room 8170, MSC 7934
Bethesda, MD 20892
Telephone: (301) 435-0447
FAX: (301) 480-1455
Email: cj68r@nih.gov

Kimberly A. McAllister, Ph.D.
Scientific Program Administrator
Susceptibility and Population Health Branch
Division on Extramural Research and Training
National Institute of Environmental Health Sciences
79 T.W. Alexander Drive
Building 4401, Room 3458
Research Triangle Park, NC 27709
Telephone: (919) 541-4528
FAX: (919) 316-4606
Email: mcallis2@niehs.nih.gov

Dina N. Paltoo, Ph.D., M.P.H.
Program Director
Division of Cardiovascular Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Rockledge II, Room 9138, MSC 7940
Bethesda, MD 20892
Telephone: (301) 435-0513
FAX: (301) 480-1335
Email: paltood@mail.nih.gov

2. Peer Review Contacts:

Valerie L. Prenger, Ph.D.
Chief, Review Branch
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Rockledge II, Room 7214, MSC 7924
Bethesda, MD 20892 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Telephone: (301) 435-0270
FAX: (301) 480-0730
Email: prengerv@nhlbi.nih.gov

3. Financial or Grants Management Contacts:

Suzanne A. White
Chief, Grants Operations Branch
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Rockledge II, Room 7160, MSC 7926
Bethesda, MD 20892
Telephone: (301) 435-0144
FAX: (301) 480-3310
Email: whitesa@nhlbi.nih.gov

Section VIII. Other Information


Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

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 NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

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

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004, receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

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.

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

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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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