and Human Services (HHS)
EXPIRED
Department of Health and Human Services
Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)
Components of Participating Organizations
National Cancer Institute (NCI), (http://www.cancer.gov/)
National Institute of Environmental Health Sciences (NIEHS), (http://www.niehs.nih.gov/)
Office of Dietary Supplements (ODS), (http://dietary-supplements.info.nih.gov/)
Title: In Utero Exposure to Bioactive Food Components and Mammary Cancer Risk (R21)
Announcement Type
This is a reissue of PA-05-059, which was previously released March 1, 2005.
Update: The following update relating to this announcement has been issued:
NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.
APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.
This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).
A registration process is necessary before submission and applicants are highly encouraged to start the process at least 4 weeks prior to the grant submission date. See Section IV.
Two steps are required for on time submission:
1) The application must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the submission/receipt date (see Key Dates below); and
2) Applicants must complete a verification step in the eRA Commons within 2 business days of notification from NIH. Note: Since e-mail can be unreliable, it is the responsibility of the applicant to periodically check on their application status in the Commons.
Program Announcement (PA) Number: PA-06-277
Catalog of Federal Domestic Assistance Number(s)
93.393, 93.396, 93.113
Key Dates
Release/Posted Date: March 24, 2006
Opening Date: May 2, 2006 (earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): Not applicable
Application Submission Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
AIDS Application Receipt Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm#AIDS.
Peer Review Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council Review Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest Anticipated Start Date: http://grants.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Additional Information To Be Available Date (URL Activation Date): Not applicable
Expiration Date: March 2, 2008 (Expired April 10, 2008 )
Due Dates for E.O. 12372
Not Applicable
Additional Overview Content
Executive Summary
The purpose of this initiative is to invite innovative preclinical R21 applications that promote research that will enhance the understanding of the relationship between exposures to bioactive food components and/or environmental chemicals in utero, hormonal and growth factor response, gene expression or epigenetic changes and subsequent mammary cancer risk in preclinical models. Although much evidence suggests that dietary components are linked to cancer prevention, the specific nutrients, sites of action, and role of exposure in utero remain elusive. Similarly, there are data suggesting a role for environmental agents, such as mycotoxins, heterocyclic amines, and environmental chemicals with endocrine activity in the etiology of mammary cancer, but for which the doses, windows of susceptibility and mechanisms are unclear. This funding opportunity encourages applications that apply new high-throughput genomic, epigenomic, proteomic, and metabolomic technologies to determine how dietary exposures in utero influence adult breast cancer susceptibility. The resulting information will help define effective maternal dietary intervention strategies for breast cancer prevention in her offspring.
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 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. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Submission, Review and Anticipated Start Dates
1. Letter of Intent
B. Electronic Transmission of 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
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
Purpose and background
In utero is a Vulnerable Period
In utero exposures are important determinants of some cancers occurring in children and young adults. For example, exposure to ionizing radiation in utero promotes childhood leukemia and maternal use of diethylstilbestrol during pregnancy has been linked to clear-cell adenocarcinoma of the vagina in their daughters. In addition, maternal diets, specifically the consumption of vegetables, fruits, and protein, are linked to decreased risk of childhood leukemia.
The prenatal period is critical in the development of the mammary gland. During this time, the mammary gland is in a largely undifferentiated state, making it particularly vulnerable to a host of environmental forces. Inappropriate nutritional status or exposure to environmental chemicals and the accompanied alteration in growth and endocrine homeostasis may permanently change the fetus' structure, physiology, and metabolism thereby predisposing it to various diseases in later life including mammary cancer.
In utero Exposures and Human Breast Cancer Risk
Epidemiological studies suggest that altering the intrauterine nutritional status can increase mammary cancer risk. Failure of the materno-placental supply line to satisfy fetal nutrient requirements can result in a range of fetal adaptations and developmental changes. Birth weight is a gross surrogate marker for shifts in a host of metabolic processes. Many, but not all, studies reveal a positive relationship between increased birth weight and breast cancer risk. Likewise, other indicators of fetal size such as increased placental weight and birth length are positively correlated with breast cancer risk in the offspring. Recent studies suggest that birth weight is independent from neonatal growth patterns and the timing of puberty as a risk factor for breast cancer.
In addition to nutrition, the hormonal environment in the womb may play an important role in programming lifelong risk for breast cancer in the female offspring. A reduction in circulating levels of estrogens and insulin like growth factor-1 (IGF-1), and/or elevated levels of progesterone, androgens, human chorionic gonadotrophin, IGF-1 binding proteins 1 and 3, cortisol ,and insulin have been associated with reduced risk. Such hormonal and growth factor changes are observed during preeclampsia. Maternal preeclampsia has been associated with a reduction in the female offspring's later risk for breast cancer after adjustment for a variety of potential confounders.
Mammary Gland Development, Dietary Modification, and Breast Cancer Risk
Proliferation of primitive ductal structures in the newborn breast leads to branching and terminal end buds (TEBs). The expansion of TEBs represents an opportunity for malignant transformation because they contain pluripotent mammary stem cells. In fact, in utero exposures that bring about an increase in TEBs coincide with increased mammary carcinogenesis. Evidence exists that providing maternal diets that contain elevated amounts of n-6 polyunsaturated fatty acids (PUFAs) and genistein not only increased TEBs, but also reduced the differentiation of TEBs to lobuloalveolar units. These diets also increased subsequent chemically induced mammary cancer in the offspring. In addition, prenatal exposures to environmental agents, such as bisphenol A or dioxin, results in alteration in the development of the mammary gland that may predispose to the development of cancers later in life. Some of this response may relate to changes in hormonal and growth factor status including estrogen and IGF-1.
Estrogen, Dietary Modification, and Breast Cancer Risk
Greater estrogen exposure throughout a woman's life has been identified as a major risk factor for the development of breast cancer. In utero exposures to the mammary gland can achieve concentrations 10-100 times the estrogen levels occurring later in life. Dietary factors, such as genistein and fat, which influence estrogen exposure to the fetus, are related to subsequent cancer risk in several model systems. However, the response may not be totally explained by estradiol, since n-3 fatty acid rich diets fed to pregnant rats, elevate this hormone, but reduce mammary cancer incidence in the offspring.
It is possible that intrauterine exposure to other hormones or environmental hormone mimics or antagonists may also affect breast cancer susceptibility. Androgen exposure in utero may confer long-term protection against breast cancer by antagonizing the effects of estrogens on fetal breast ductal development. Dietary fatty acids, phytoestrogens, alcohol, and lycopene are among the various bioactive food components reported to influence androgen concentrations. Environmental agents with estrogenic agonist or antagonist activity may also alter gene expression during development that may lead to functional deficits later in life that predispose to cancer development. Thus, there is the need for future studies focusing on uncovering the mechanisms responsible for the protective and detrimental effects of exposure to bioactive food components and other environmental agents in utero on breast cancer risk. These studies should attempt to address more comprehensively the changes in all potentially relevant pregnancy hormones and growth factors.
IGF, Dietary Modification, and Breast Cancer Risk
The IGF-1 system may play a crucial role in the increased risk that heavier newborns have of developing breast cancer later in life. Birth weight is positively associated with increased insulin and IGF-1 concentrations. Analysis of mammary gland development in knockout mice made deficient in IGF-I or in the IGF-I receptor demonstrates the importance of the IGF system for normal mammary gland development because these mice have diminished TEB development. Observational and preclinical studies provided added evidence that one or more components of the IGF-1 system may be intimately linked to the process of carcinogenesis in the mammary gland. Transgenic mice that overexpress IGF-I or -II display specific alterations in mammary gland development such as an inhibition of mammary cell apoptosis following weaning and an increased incidence of mammary tumors. Thus, increased exposure to IGF-1 in utero may serve as a marker for the relationship between fetal growth and adult cancer susceptibility.
Although the effects of in utero exposure to dietary components have been inadequately examined, considerable evidence exists for their ability to modify IGF-1 concentrations and mammary cancer susceptibility postnatally. Postnatal caloric restriction decreases IGF-1 and decreases mammary tumor growth and metastases. Furthermore, postnatal soy phytochemicals combined with green tea synergistically inhibited mammary tumor growth and depressed serum IGF-1 levels in mice. Future studies are warranted to determine whether in utero exposure to dietary manipulations that modulate IGF-1 expression will influence subsequent breast cancer risk.
Epigenetics, Dietary Modification, and Breast Cancer Risk
Maternal nutritional status can also alter the epigenetic state of the fetal genome and imprint gene expression levels with lifelong consequences. Loss of imprinting is the silencing of active imprinted genes or the activation of silent imprinted genes, and is one of the most common epigenetic changes associated with the development of a wide variety of tumors. For example, loss of imprinting of IGF-2 has been associated with many different types of cancer including mammary tumor development. H19, a tumor suppressor gene located directly downstream from IGF-2, is also genomically imprinted, and is associated with various cancers. Furthermore, the hereditary disorder Beckwith-Wiedemann syndrome, which predisposes to cancer and causes prenatal overgrowth, involves alterations in IGF-2 and H19 imprinting. Several lines of evidence support the relationship between maternal nutrition and epigenetic changes in their offspring. First, a deficiency of amino acids results in marked reduction in genomic DNA methylation and aberrant expression of the normally silent paternal H19 allele in cultured mouse embryos. Second, uteroplacental insufficenty causes hypomethylation and increased histone acetylation in postnatal rat liver. Third, maternal supplementation of methyl donors and cofactors (folic acid, vitamin B-12, choline and betaine) increases CpG methylation at the Avy locus of agouti mouse pups which causes a shift from a yellow to an agouti coat. The methylation patterns are retained into adulthood and are linked with a lower risk of cancer, diabetes, obesity, and prolonged life. Thus, epigenetic changes may provide a molecular mechanism for the impact of maternal nutrition or environmental chemical exposures on postnatal disease susceptibility and deserves future research.
Objectives and scope
Investigators may choose from the full range of preclinical approaches. The use of genetically engineered animal models including transgenic or knockouts, such as those available through the mouse models of human cancer consortium (MMHCC, http://emice.nci.nih.gov/), are encouraged. Studies are encouraged that apply new high-throughput genomic, epigenomic, proteomic, and metabolomic technologies to determine how dietary and/or environmental chemical exposures in utero influence adult breast cancer susceptibility.
Illustrative examples for the development of R21 applications include, but are not limited to, the following examples:
See Section VIII, Other Information - Required Federal Citations for policies related to this announcement.
Section II. Award Information
1. Mechanism of Support
This FOA will use the NIH Exploratory/Developmental Research Grant (R21) award mechanism. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.
This FOA uses just-in-time concepts. It also uses the modular budget formats (see the Modular Applications and Awards section of the NIH Grants Policy Statement. Specifically, if you are submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs), use the PHS398 Modular Budget component provided in the SF424 (R&R) Application Package and SF424 (R&R) Application Guide (see specifically Section 5.4, Modular Budget Component, of the Application Guide).
Exploratory/developmental grant support is for new projects only; competing renewal (formerly competing continuation ) applications will not be accepted. Up to two resubmissions (formerly revisions/amendments") of a previously reviewed exploratory/developmental grant application may be submitted. See NOT-OD-03-041, which was published in the NIH Guide on May 7, 2003.
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 NIH Institutes and Centers (ICs) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.
The total project period for an application submitted in response to this funding opportunity may not exceed 2 years. Although the size of award may vary with the scope of research proposed, it is expected that applications will stay within the budgetary guidelines for an exploratory/developmental project; direct costs are limited to $275,000 over an R21 2-year period, with no more than $200,000 in direct costs allowed in any single year. Applicants may request direct costs in $25,000 modules, up to the total direct costs limitation of $275,000 for the combined 2-year award period. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this Program Announcement funding opportunity.
Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004, which was published in the NIH Guide.
Section III. Eligibility Information
1. Eligible Applicants
1.A. Eligible Institutions
You may submit (an) application(s) if your organization has any of the following characteristics:
1.B. Eligible Individuals
Any individual with the skills, knowledge, and resources necessary to carry out the proposed research 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.
2. Cost Sharing or Matching
Not applicable This program does not require cost sharing as defined in the current NIH Grants Policy Statement.
The most current Grants Policy Statement can be found at: http://grants.nih.gov/grants/policy/nihgps_2003/nihgps_Part2.htm#matching_or_cost_sharing.
3. Other-Special Eligibility Criteria
Applicants may submit more than one application, provided each application is scientifically distinct.
Section IV. Application and Submission Information
Registration and Instructions for Submission via Grants.gov
To download a SF424 (R&R) Application Package and SF424 (R&R) SBIR/STTR Application Guide for completing the SF424 (R&R) forms for this FOA, link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.
A one-time registration is required for institutions/organizations at both:
PDs/PIs should work with their institutions/organizations to make sure they are registered in the eRA Commons.
Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows:
1) Organizational/Institutional Registration in Grants.gov/Get Started
2) Organizational/Institutional Registration in the eRA Commons
3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.
Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.
Several of the steps of the registration process could take 4 weeks or more. Therefore, applicants should immediately check with their business official to determine whether their institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.
1. Request Application Information
Applicants must download the SF424 (R&R) application forms and SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.
Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.
For further assistance, contact GrantsInfo; Telephone: 301-710-0267, E-mail: [email protected].
Telecommunications for the hearing impaired: TTY 301-451-5936.
2. Content and Form of Application Submission
Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide (MS Word or PDF).
The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH (e.g., the Credential log-in field of the Research & Related Senior/Key Person Profile component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see Tips and Tools for Navigating Electronic Submission on the front page of Electronic Submission of Grant Applications.
The SF424 (R&R) application is comprised of data arranged in separate components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY will include all applicable components, required and optional. A completed application in response to this FOA will include the following components:
Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
Research & Related Budget
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget
Optional Components:
PHS398 Cover Letter File
Note: While both budget components are included in the SF424 (R&R) forms package, the NIH R21 uses ONLY the PHS 398 Modular Budget. (Do not use the detailed Research & Related Budget.)
Foreign Organizations:
Several special provisions apply to applications submitted by foreign organizations:
Proposed research should provide a unique research opportunity not available in the United States.
3. Submission Dates and Times
See Section IV.3.A for details.
3.A. Submission, Review, and Anticipated Start Dates
Opening Date: May 2, 2006
Letter of Intent Receipt Date: Not applicable
Application Submission Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm
AIDS Application Submission Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm#AIDS
Peer Review Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm
Council Review Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm
Earliest Anticipated Start Date9S0: http://grants.nih.gov/grants/funding/submissionschedule.htm
3.A.1. Letter of Intent
A letter of intent is not required for the funding opportunity.
3.B. Electronic Transmission of an Application to the NIH
To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/Apply and follow steps 1-4. Note: Applications must only be submitted electronically.
PAPER APPLICATIONS WILL NOT BE ACCEPTED.
3.C. Application Processing
Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application submission/receipt date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the receipt date(s) and time, the application may be delayed in the review process or not reviewed.
Upon receipt, applications will be transferred from Grants.gov to the NIH Electronic Research Administration process for validation. Both the PD/PI and the Signing Official (SO) for the organization must verify the submission via Commons within 2 business days of notification of the NIH validation.
Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Incomplete applications will not be reviewed.
There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. Information related to the assignment of an application to a Scientific Review Group is also in the Commons.
The NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of an application already reviewed with substantial changes, but such application must include an Introduction addressing the previous critique. Note such an application is considered a "resubmission" for the SF424 (R&R).
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.
6. Other Submission Requirements
The NIH requires the PD/PI to fill in his/her Commons User ID in the PROFILE Project Director/Principal Investigator section, Credential log-in field of the Research & Related Senior/Key Person Profile component. The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Tips and Tools for Navigating Electronic Submission on the front page of Electronic Submission of Grant Applications.
Renewal (formerly competing continuation or Type 2 ) applications are not permitted.
All application instructions outlined in the SF424 (R&R) application are to be followed, with the following requirements for R21 applications:
Note: While each section of the Research Plan needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.
o Up to five publications, manuscripts (accepted for publication), abstracts, patents, or other printed materials directly relevant to this project. Do not include manuscripts submitted for publication.
- Publications in press: Include only a publication list with a link to the on-line journal article or the PubMed Central (PMC) submission identification number. Do not include the entire article.
- Manuscripts accepted for publication, but not yet published: The entire article may be submitted electronically as a PDF attachment.
- Manuscripts published but an online journal link is not available: The entire article may be submitted electronically as a PDF attachment.
o Surveys, questionnaires, data collection instruments, clinical protocols, and informed consent documents.
o Graphic images of gels, micrographs, etc., provided that the image (may be reduced in size) is also included within the 15-page limit of Items 2-5 of the Research Plan. No images may be included in the Appendix that are not also represented within the Research Plan.
o Do not use the Appendix to circumvent the page limitations of the Research Plan. An application that does not observe these limitations may be delayed in the review process.
Plan for Sharing Research Data
Not applicable
Sharing Research Resources
NIH policy requires that grant awardee 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 at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.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). See Section VI.3., Reporting.
Section V. Application Review Information
1. Criteria
Only the review criteria described below will be considered in the review process.
2. Review and Selection Process
Applications submitted for this funding opportunity will be assigned to the NIH ICs on the basis of established PHS referral guidelines.
Appropriate scientific review groups convened in accordance with the standard NIH peer review procedures (http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific and technical merit.
Applications that are complete will be evaluated for scientific and technical merit by an appropriate review group convened by the NIH Center for Scientific Review in accordance with the review criteria stated below.
As part of the initial merit review, all applications will:
Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications. The following will be considered in making funding decisions:
The NIH R21 exploratory/developmental grant is a mechanism for supporting novel scientific ideas or new model systems, tools, or technologies that have the potential to significantly advance our knowledge or the status of health-related research. Because the Research Plan is limited to 15 pages, an exploratory/developmental grant application need not have extensive background material or preliminary information as one might normally expect in an R01 application. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Reviewers will place less emphasis on methodological details and certain indicators traditionally used in evaluating the scientific merit of R01 applications, including supportive preliminary data. 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.
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?
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?
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?
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 PD/PI 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?
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:
Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under item 11 of the Research Plan component of the SF 424 (R&R) will be assessed.
2.B. Additional Review Considerations
Budget and Period of Support: The reasonableness of the proposed budget and the appropriateness of the requested period of support in relation to the proposed research may be assessed by the reviewers. Is the effort listed for the PD/PI appropriate for the work proposed? Is each budget category realistic and justified in terms of the aims and methods?
2.C. Sharing Research Data
Not applicable
2.D. Sharing Research Resources
NIH policy requires that grant awardee 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 at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.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.
Program staff will be responsible for the administrative review of the plan for sharing research resources.
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), See Section VI.3., Reporting.
3. Anticipated Announcement and Award Dates
Not applicable
Section VI. Award Administration Information
1. Award Notices
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the NIH eRA Commons.
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.
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 e-mail notification from the awarding component to the grantee 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 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 and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities.
2.A. Cooperative Agreement Terms and Conditions of Award
Not applicable.
3. Reporting
When multiple years are involved, awardees will be required to submit the Non-Competing Grant Progress Report (PHS 2590) annually 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:
National Cancer Institute (NCI)
Cindy D. Davis, Ph.D.
Division of Cancer Prevention
National Cancer Institute
6130 Executive Boulevard, EPN Room 3159, MSC 7328
Bethesda, MD 20892-7328 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery)
Telephone: (301) 594-9692
FAX: (301) 480-3925
E-mail: [email protected]
NIH Office of Dietary Supplements (ODS)
Mary Frances Picciano, Ph.D., R.D.
Office of Dietary Supplements
Office of the Director
National Institutes of Health
6100 Executive Boulevard, Room 3B01, MSC 7517
Bethesda, MD 20892-7517 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery)
Telephone: 301-435-3608
E-mail: [email protected]
National Institute of Environmental Health Sciences (NIEHS)
Jerry Heindel, Ph.D.
Cellular, Organs and Systems Pathobiology Branch
Division of Extramural Research and Training
POB 12233 RTP, NC, 27709
79.T.W. Alexander Drive, 4401 bldg. (for express/courier service)
Telephone: 919-541-0781
FAX: 919-541-5064
E-mail: [email protected]
2. Peer Review Contacts:
Not applicable
3. Financial or Grants Management Contacts:
Connie Murphy
Office of Grants Administration
National Cancer Institute
6120 Executive Boulevard
Executive Plaza South, Room 243, MSC 7150
Bethesda, MD 20892-7150 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery)
Phone: (301) 496-8657
FAX: (301) 496-8601
E-mail: [email protected]
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.
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 institutional review board (IRB) rules, as well as local, State, and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan, but will not factor the plan into the determination of the scientific merit or the priority score.
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 at http://grants.nih.gov/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.
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).
URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.
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 percent of their time (at least 20 hours per week based on a 40-hour week) for 2 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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