Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Institute of Environmental Health Sciences (NIEHS) National Cancer Institute (NCI) National Heart, Lung, and Blood Institute (NHLBI) National Human Genome Research Institute (NHGRI) National Institute of Biomedical Imaging and Bioengineering (NIBIB) National Institute on Dental and Craniofacial Research (NIDCR) National Institute on Drug Abuse (NIDA) National Library of Medicine (NLM)
Funding Opportunity Title	Methods and Approaches for Detection of Gene-Environment Interactions in Human Disease (R21)
Activity Code	R21 Exploratory/Developmental Research Grant Award
Announcement Type	New
Related Notices	None
Funding Opportunity Announcement (FOA) Number	PAR -11-032
Companion FOA	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestics Assistance (CFDA) Number(s)	93.113
FOA Purpose	This FOA issued by NIEHS, National Institutes of Health, encourages grant applications from institutions/organizations to develop and test innovative statistical and bioinformatics methods and analytical strategies and study designs for identifying gene-environment interactions for complex human diseases. The objectives of this FOA are to further advance the understanding of gene-environment interplay in complex human disease by 1) the development and validation of algorithms and new statistical and computational approaches and study designs and/or 2) the development and application of bioinformatics software for gene-environment analysis of existing human populations.

Posted Date	November 12, 2010
Open Date (Earliest Submission Date)	January 3, 2011
Letter of Intent Due Date	January 4, 2011
Application Due Date(s)	February 3, 2011, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	June/July 2011
Advisory Council Review	October 2011
Earliest Start Date(s)	December 2011
Expiration Date	February 4, 2011
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

The overall goal of this FOA is to develop and test innovative statistical, analytical, and bioinformatics methods and approaches for identifying gene-environment interactions for complex human diseases. Although gene-environment (G x E) interaction can be described in a variety of ways, for the purposes of this FOA, it is defined as any joint effect of one or more genes with one or more environmental factors or exposures that cannot be easily explained by their separate marginal effects. The objectives of this FOA are to further advance the understanding of gene-environment interplay in complex human disease by supporting the further development of analytical methods and tools for gene-environment studies to the field of environmental health sciences. The long-term goal of this initiative is to help identify individuals at highest risk for developing a specific disease or dysfunction based on both their exposure patterns and genetic risk profiles and inform potential environmental modifications or behavioral change interventions that could be implemented to prevent or reduce disease burden. For the purposes of this FOA, environmental risk factors or exposures can refer to chemical toxicants, such as metals and solvents, and biological agents, such as toxins. Lifestyle factors such as diet, physical activity, and the use of addictive substances will also be considered. 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. In addition to NIEHS, multiple other NIH Institutes are participating in this FOA. NCI encourages applications that address novel statistical methods, computational and analytical tools, and designs for studying interactions of genetic and environmental factors for studies of cancer etiology and prognosis. Applications may include statistical methods for large-scale gene-environment analysis of disease pathways for cancer risk assessment, early detection, prevention, and outcome. NCI is also interested in studies of the interaction of the environment with early cancer biomarkers. NIDCR encourages applications that address analytic, statistical, or computational issues in gene-environment interaction relevant to oral health, or dental or craniofacial conditions or diseases. NHGRI encourages development or improvement of statistical and computational methods to analyze and integrate genetic and environmental data for broad use across a variety of diseases, conditions, or traits. NLM emphasizes innovation in computational methods and data integration relevant to G x E interactions. NIDA is interested in development and application of methodologies and tools for studying the relationship of genetic and environmental interactions in substance abuse initiation, persistence, cessation, and relapse. NIBIB is interested in supporting the development and application of novel modeling, analysis, and simulation technology for identifying gene-environment interactions for complex human diseases. In particular NIBIB is interested in promoting the development and application of predictive multi-scale models in this area. NHLBI encourages applications that address the development or improvement of novel statistical methods, as well as computational resources and tools, for the analysis and integration of genetic and environmental data relevant to heart, lung, blood, or sleep diseases and disorders.

Much of the burden of health for the U.S. and other developing countries 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. Multiple genes and environmental factors acting in interconnected biological pathways or networks are thought to contribute to the susceptibility and progression of these complex human diseases. The complexity of the genotype phenotype relationships in most common complex diseases will require an understanding of genetic and clinical heterogeneity and gene gene and gene environment interactions. Unfortunately, the analytical and computational approaches and study designs for identifying gene-environment interactions in complex diseases are limited.

Genome-wide association studies have emerged as a powerful new tool in recent years for identifying genetic variants to complex diseases. However, most analytical approaches adopted for whole genome scans do not incorporate environmental factors into the analysis, and the great majority of genetic variants identified with genome-wide association studies (GWAS) thus far are of little clinical validity since they confer only a small increased risk of the disease they associate with. Although many GWAS datasets have not collected data on environmental factors, some are based on epidemiologic cohorts or case control studies that have exposure information and could be utilized further for novel G E interaction discoveries.

Gene-environment interactions that have been identified thus far suggest that environmental exposures may help identify susceptible subpopulations for disease risk (ex. NAT2 x smoking for bladder cancer risk, IL10 x dust mite exposure for asthma/allergy). Identification of gene and environment interplay is also being recognized as an avenue to further understand the biological networks underlying complex disease risks. Incorporation of environmental risk factors in large-scale genome analyses can enhance detection of genetic effects and is necessary to characterize the impact of joint effects on disease risk. The ultimate success of GWAS studies and other gene discovery techniques for contributing to targeted therapies, interventions, or preventive strategies for complex diseases will therefore depend on further development of methods and analytical tools that can incorporate and analyze the role of environment in these diseases. Understanding the interplay of genetic variants and environmental exposures in complex disease outcomes will improve disease risk prediction as well. Furthermore, the genetic variants most easily translated for public health or clinical utility will be those that have an obvious corresponding environmental modification identified that will be capable of altering the disease risk.

A variety of workshops that NIEHS and other NIH Institutes have held in recent years, including multiple NIH Genes, Environment and Health Initiative (GEI)-sponsored workshops (http://www.gei.nih.gov/), have stressed the importance of the further development of analytical tools for gene and environment interaction studies. One GEI-supported workshop (held in 2008), entitled "Genome-Wide Association: Analyze This!", specifically focused on statistical strategies to identify environmental components or covariates of disease and their interactions with genes in genome-wide association studies. Many statistical, bioinformatics, and software development challenges have repeatedly been identified as barriers in the further understanding of the complex gene-environment interactions of many common human diseases. In addition, a trans-NIH workshop entitled Next Generation Analytical Tools for Large Scale Genetic Epidemiology Studies of Complex Diseases (held in mid-September 2010) was focused partly on statistical and analytical strategies and methods to efficiently identify genetic and environmental factors contributing jointly to complex disease risk. Particular areas of continued challenge in this field that were emphasized at this workshop include: sample size issues, accurate environmental exposure measurements, efficient analytic approaches, and feasible computational approaches. The many challenges of incorporating non-static exposure measurements and assessments into population study designs were especially highlighted at this meeting. A defined initiative in this area also builds on an earlier gene-environment interaction methods initiative that was a component of the first phase of GEI. Resources (including statistical software package descriptions and publications) generated from this initiative (RFA-HL-07-010) can be accessed through the GEI home page (http://www.gei.nih.gov/). Although the statistical methods for G x E identification and analysis have improved in the past few years with this and other similar efforts, many challenges and unmet needs in this field still exist, particularly in the areas of: the data integration of diverse data types, approaches to incorporate meta-analyses and consortium data, bioinformatics approaches applied to efficient detection of G x E interactions, and the greater representation of approaches and study designs to incorporate multiple or continuous environmental exposures into genetic epidemiological studies. Many environmental exposures are time-varying covariates (ex. environmental factors such as diet, physical activity, and some common exposures such as air pollution) that are known to change over time but methods to best incorporate this data into G x E studies for complex human disease phenotypes have been limited to date.

This FOA is especially appropriate at this time with the current analysis of many GWAS studies and further interest in utilizing existing GWAS datasets for additional secondary analyses that can incorporate environmental risk factors. The initial phase of the GEI program is also ending and the further development of better tools to identify gene-environment interactions is recognized by NIH as an additional intermediate step necessary before efforts to utilize large-scale population studies (particularly longitudinal) that incorporate many environmental exposure measurements can be fruitful. There is also the recognized need for approaches to adapt G x E methods to the meta-analytic framework given the focus on large consortium efforts for complex disease phenotypes in recent years.

NIH particularly encourages the development and application of new tools and computational approaches for gene-environment interaction studies to further leverage existing human population studies previously utilized for GWAS and other genetic discoveries. The development of optimal study designs to detect gene-environment interactions in different types of epidemiologic studies is particularly needed. Applicants that develop and apply approaches incorporating long-term exposures that change over time, which may indicate certain windows of vulnerability or susceptibility, are especially encouraged to apply to this FOA. The incorporation of temporal and spatial environmental exposure variations into analytical strategies is needed to appropriately capture many exposures that cannot be accurately reflected with just one exposure time point or by simply categorizing individuals into static exposure categories. The exploration and application of methods to account for multiple exposure effects or mixtures for G x E interaction discovery is also sorely lacking. In addition, the incorporation of prior knowledge about disease pathobiology and gene function is encouraged to computationally model the relationship between genetic variations and environmental exposures with disease susceptibility as applied to human population datasets. The increasingly complex role of environmentally-induced epigenetic effects on complex disease risk also needs to be incorporated into G x E analytical methods and study designs. Appropriate topics include but are not limited to those listed below:

• New statistical methods to identify gene-environmental interactions that lead to distinct molecular phenotypes (e.g., gene expression).
• Statistical and bioinformatics approaches for incorporation of high dimensional genetic and environmental data for discovery and analysis of gene-environment interactions.
• Novel approaches to using biological pathway and gene function information or other biological data in studies of G x E interaction discovery.
• Designs and methods for reducing and accounting for environmental exposure measurement error that significantly reduce the power to detect gene-environment interactions in human population studies.
• Novel approaches and study designs for more effective sampling of a broader range of an environmental exposure and other novel study approaches designed to increase power and efficiency for detecting gene-environment interactions.
• Efficient methods to test G x E interactions in the meta-analytic framework.
• Statistical methods to analyze continuous traits related to a human disease or disorder with multiple genetic and environmental components.
• Incorporation of systems biology tools to aid in analysis and interpretation of gene-environment data as applied to human population datasets.
• Computational methods for data mining and machine learning and bioinformatics methods for incorporating prior biological and toxicological knowledge into data analysis algorithms for identification of gene-environment interactions.
• Analytical or bioinformatics tools for data integration (between studies and datasets) and harmonization of environmental data to allow gene-environment investigations in larger human population datasets.
• Development and application of study designs for gene-environment interactions when using biomarkers as exposure surrogates.
• Computational and bioinformatics approaches to better utilize family studies for gene-environment interaction discovery.
• The development and application of approaches utilizing admixed populations to help identify G x E interactions in complex diseases.
• Statistical and analytical methods that allow for incorporation of continuous, accumulating, and/or long-term exposure measurements of environmental exposure(s) combined with multiple genetic components for risk of disease.
• Approaches to integrate individual-level data (from biomarkers, genotypes, and questionnaires, etc.) with population or aggregate-level data (GIS or geocoding, etc.) for detection of novel G x E interaction effects.
• Approaches to integrate and apply many different data types (pharmacogenetics, metabolomics, gene expression data, epigenetics, etc.) to inform gene-environment interplay in complex human diseases.
• Study designs that best exploit gene-environment interactions for prenatal effects.
• Novel methods and analytical approaches allowing the incorporation of exposure assessment tools (such as biomarkers of biological response to environmental stressors and environmental sensors for exposure assessment) with genetic factors for complex disease risk.

Funding Instrument	Grant
Application Types Allowed	New The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications.
Award Budget	Direct costs are limited to $300,000 over a R21 3-year period, with no more than $200,000 in direct costs allowed in any single year and a combined budget for direct costs for any 2-year project period may not exceed $275,000.
Award Project Period	Scope of the proposed project should determine the project period. The total project period for an application submitted in response to this funding opportunity may not exceed 3 years.

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

Higher Education Institutions:

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

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

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions

Nonprofits Other Than Institutions of Higher Education

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

For profit Organizations

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

Governments

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

Other

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

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

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• Grants.gov
• eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

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

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

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

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

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

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.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

Descriptive title of proposed research
Name, address, and telephone number of the PD(s)/PI(s)
Names of other key personnel
Participating institutions
Number and title of this funding opportunity

The letter of intent should be sent to:

Kimberly A. McAllister, PhD
Program Official
Susceptibility and Population Health Branch
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
Keystone Building, MD K3-12
P.O. Box 12233
Research Triangle Park, NC 27709-2233
Phone: (919) 541-4528
Fax: (919) 316-4606
Email: [email protected]

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

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

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Exploratory novel approaches in these three-year R21s should be tested, shared, and made available through open access software whenever possible.

For the scientific community to benefit the most from this NIH initiative, investigators of this funding opportunity are expected to provide available user-friendly software packages and documentation that can be used jointly by researchers with expertise in experimental biology and researchers with expertise in statistics and computer science.

Meetings will be held once a year to encourage sharing of statistical methods and approaches for different study designs. Applicants are advised to include the cost for such a meeting in the budget.

Given budget constraints, this FOA will support the use of existing human population studies only. Applications that include the recruitment of human subjects, new collection of biological samples, and/or new collection of phenotypic and other medical data are not appropriate for this announcement. Applicants are expected to document access to existing DNA samples, environmental exposures, and phenotypic data from existing human studies. Applications that do not have a clear environmental exposure identified are not appropriate for this announcement. 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.

Additionally, applicants should provide strong justification for the choice of study design and methodological, analytical, or bioinformatics strategy proposed.

Although simulated datasets can be utilized in the application for development of methods and approaches for detecting gene-environment interactions, all applications must also include appropriate existing human population datasets as well to apply the methods or approaches proposed. (The use of simulated data alone is not appropriate for this announcement.

Resource Sharing Plan

Individuals are expected to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS) as provided in the SF424 (R&R) Application Guide.

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix

Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

Applicants are responsible for viewing their application in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD/PIs must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the Central Contractor Registration (CCR). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s)

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

Innovation

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

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

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

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.

Protections for Human Subjects

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

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable.

Renewals

Not Applicable.

Revisions

Not Applicable.

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

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review (assignments will be shown in the eRA Commons), in accordance with NIH peer review policy and procedures, using the stated review criteria.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review), will be discussed and assigned an overall impact/priority score.
• Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA . Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board . The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. 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.

Any application awarded in response to this FOA will be subject to the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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 and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

Not Applicable.

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

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

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

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Contact Center Phone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: [email protected]

Kimberly A. McAllister, PhD
National Institute of Environmental Health Sciences (NIEHS)
Telephone: (919) 541-4528
Email: [email protected]

Leah Mechanic, PhD, MPH
National Cancer Institute (NCI)
Telephone: 301-496-8105
Email: [email protected]

Dina N. Paltoo, PhD, MPH
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: (301) 435-0513
Email: [email protected]

Erin M. Ramos, PhD, MPH
National Human Genome Research Institute (NHGRI)
Telephone: (301) 451-3706
Email: [email protected]

Grace C.Y. Peng, PhD
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Telephone: (301) 451-4778
Email: [email protected]

Joni L. Rutter, PhD
National Institute on Drug Abuse (NIDA)
Telephone: (301) 435-0298
Email: [email protected]

Emily L. Harris, PhD, MPH
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: (301) 594-4846
Email: [email protected]

Jane Ye, PhD
National Library of Medicine (NLM)
Telephone: (301) 594-4882
Email: [email protected]
Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Wanda Boggs
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 919-316-4638
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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 Part 52 and 45 CFR Parts 74 and 92.