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 on Alcohol Abuse and Alcoholism (NIAAA), (http://www.niaaa.nih.gov/)
National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), (http://www.niddk.nih.gov/)
Office of Dietary Supplements (ODS), (http://dietary-supplements.info.nih.gov)
Title: Diet, Epigenetic Events, and Cancer Prevention (R03)
Announcement Type
This is a reissue of PA-04-099,
which was previously released April 30, 2004, and now is divided into
separate FOAs for R03, R21, and R01 grant funding mechanisms.
Update: The following update relating to this announcement has been issued:
NOTICE: Applications submitted in response to this 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 should be started at least 4 weeks in advance of the planned submission. See Section IV.
Program
Announcement (PA) Number: PA-06-414
Catalog of Federal
Domestic Assistance Number(s)
93.393, 93.396, 93.273, 93.848
Key Dates
Release/Posted Date: May 16, 2006
Opening Date: May 16, 2006 (earliest date an application may be submitted to Grants.gov).
Letters of Intent Receipt Date(s): Not
applicable.
NOTE: On time submission requires that applications be successfully
submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant
institution/organization).
Application Submission/Receipt Date(s): Standard dates
apply, please seehttp://grants1.nih.gov/grants/funding/submissionschedule.htm
AIDS
Application Submission/Receipt Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#AIDS.
Peer Review
Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council
Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest
Anticipated Start Date(s): Standard
dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Additional Information To Be Available Date
(URL Activation Date): Not applicable.
Expiration Date: September 2, 2009 (now September 8, 2009 per NOT-OD-07-093)
Due Dates
for E.O. 12372
Not Applicable.
Additional Overview
Content
Executive Summary
The aim of this funding opportunity announcement (FOA) is to promote clinical and preclinical research to determine how diet and dietary factors, including dietary supplements, impact DNA methylation, histone posttranslational modification, and other epigenetic processes involved in cancer prevention and development. Another important aim of this FOA is to encourage collaborations between nutrition and epigenetic experts to study bioactive food components with cancer-preventative properties and to examine key epigenetic events in cancer processes (e.g., carcinogen metabolism, cell division, differentiation, and apoptosis) in order to begin to establish linkages between epigenetics, methylation patterns, and tumor incidences/behaviors. NIAAA is specifically interested in receiving applications that examine the impact(s) of chronic alcohol consumption on levels of SAM, betaine, and folate, and possible associations with DNA methylation and cancer. NIDDK is particularly interested in receiving applications that address normal and neoplastic conditions focusing on the impact of epigenetics on cell division, differentiation, and/or apoptosis in the GI tract and related organs.
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. Sending an Application to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements
Section V. Application Review
Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Sharing Research Data
D. Sharing Research Resources
3. Anticipated Announcement and Award Dates
Section VI. Award Administration
Information
1. Award Notices
2. Administrative and National Policy
Requirements
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
The purpose of this funding opportunity announcement (FOA) is to promote innovative preclinical and clinical research to determine how diet and dietary factors, including dietary supplements, impact epigenetic processes involved in cancer prevention. Although much evidence exists that dietary components are linked to cancer prevention, the specific nutrients and sites of action remain elusive. Diet, in fact, has been implicated in many of the pathways of cancer, including apoptosis, cell cycle control, differentiation, inflammation, angiogenesis, DNA repair, and carcinogen metabolism. These are also processes that are likely regulated by epigenetic events to impact gene function and chromatin stability. Thus, research supported by this initiative could address one of the following issues: how bioactive food components regulate epigenetic events for cancer prevention, how bioactive food components might alter aberrant epigenetic patterns or events and restore gene function, and how these components might circumvent or compensate for genes and pathways that are altered by epigenetic events. Another important aim of this FOA is to encourage collaborations between nutrition scientists and experts in epigenetics to study bioactive food components with cancer-preventative properties and to examine key epigenetic events in cancer processes (e.g., carcinogen metabolism, cell division, differentiation, and apoptosis) in order to begin to establish linkages between epigenetic events and patterns, and tumor incidences/behaviors. NIDDK is particularly interested in receiving applications that address normal and neoplastic conditions focusing on the impact of epigenetics on cell division, differentiation, and/or apoptosis in the gastrointestinal (GI) tract and related organs. It is also expected that each application demonstrate experience in nutrition and cancer prevention as well as in epigenetic research.
Cancer is a manifestation of both abnormal genetic and epigenetic events. Epigenetic events represent important mechanism(s) by which gene function is selectively activated or inactivated. DNA methylation is the covalent addition of a methyl group to the 5 position of cytosine within CpG dinucleotides and is a fundamental process that not only modulates gene expression, but also is key to regulating chromosomal stability. Fluctuations in the degree of CpG island methylation are key to regulating functional promoters by modifying the binding of transcription factors and methyl-DNA binding proteins. A variety of regulatory proteins including DNA methyltransferases, methyl-CpG binding proteins, histone modifying enzymes, chromatin remodeling factors, and their multimolecular complexes are involved in the overall epigenetic process. Since epigenetic events are susceptible to change, they represent excellent targets to explain how environmental factors, including diet, may modify cancer risk and tumor behavior. Abnormal DNA methylation patterns are a hallmark of most cancers, including those of high prevalence in the United States, i.e., colon, lung, prostate, and breast cancer.
Preclinical and clinical studies provide intriguing evidence that part of the anticancer properties attributed to several bioactive food components, encompassing both essential and non-essential nutrients, may relate to modulation of epigenetic processes, including DNA methylation. There are at least four ways in which nutrients may be interrelated with DNA methylation. The first is that nutrients may influence the supply of methyl groups for the formation of S-adenosylmethionine (SAM). The second mechanism is that nutrients may modify utilization of methyl groups by processes including shifts in DNA methyltransferase activity. A third plausible mechanism may relate to DNA demethylation activity. Finally, the DNA methylation patterns may influence the response to a nutrient.
Emerging evidence indicates that various chromatin states such as histone modifications (acetylation and methylation) and nucleosome positioning (modulated by ATP-dependent chromatin remodeling machines) determine DNA methylation patterning. Histone modifications have recently generated a great deal of excitement in epigenetic research, culminating in the histone code hypothesis. Evidence suggests that butyrate, which is formed in the large intestine by fermentation of dietary fiber, may mediate gene expression by encouraging interactions between a DNA binding protein and a histone acetyltransferase. For example, the zinc-finger binding protein-89, a DNA-binding protein that binds GC-rich sites, has been found to mediate butyrate-induced expression of the p21waf1 gene through interaction of p300 (a histone acetyltransferase) with subsequent recruitment of the transcriptional activator Sp1 to this complex. Recent findings have also implicated bioactive food components, including sulforaphane from cruciferous vegetables, diallyl disulfide from garlic, and genistein from soy, as weak inhibitors of histone deacetylases. More mechanistic studies are needed to characterize additional gene-specific histone modifications brought about by bioactive food components.
Alcohol, DNA
Methylation, and Cancer
In vivo chronic ethanol exposure of animals impairs methionine metabolism by decreasing the activities of methionine synthase and methionine adenosyltransferase (MAT). It also depletes hepatic folate, which is a source of methyl group for remethylation of homocysteine, and depletes liver betaine, an alternate source of methyl groups. The ultimate effect of these changes is decreased levels of SAM and increased levels of homocysteine. Elevated levels of homocysteine results in increased intracellular levels of S-adenosyl homocysteine (SAH) through a reversible reaction catalyzed by SAH hydrolase. Studies in animals have shown that chronic ethanol exposure can increase intracellular level of SAH which is a potent inhibitor of several methyltransferases including DNA methyltransferases, which catalyze the transfer of methyl group from SAM to DNA. Depletion of SAM levels and inhibition of DNA methyltransferases activity by chronic alcohol exposure can lead to DNA hypomethylation, which could in turn play an important role in carcinogenesis. A connection between SAM depletion and cancer has been demonstrated in SAM-deficient MAT1A knockout mice which develop hepatocellular carcinoma (HCC). In addition, dietary SAM supplementation has been shown to reduce hepatic neoplastic nodules in animal models of HCC. Another dietary source of methyl group, betaine (trimethylglycine), has been shown to increase levels of SAM and decrease levels of SAH in livers of rats chronically exposed to alcohol. Thus, betaine is potentially capable of partially improving DNA methylation by increasing SAM levels and by rescuing DNA methyltransferases from the inhibitory effect of SAH.
Additional Research
Objectives
Studies submitted in response to this FOA should link phenotypic changes to
epigenetic alterations induced by specific bioactive food components. The
resulting information will be critical for optimizing effective dietary intervention
strategies for cancer prevention. Investigators may choose from the full range
of clinical and preclinical approaches. The focus should be on how individual
dietary components influence epigenetic events and how this correlates with
phenotypic change. Very little information currently exists about gene-specific
epigenetic changes as influenced by bioactive food components; furthermore,
very little information exists to adequately evaluate the specificity of
individual nutrients, the impact of intakes/exposures, and any acclimation with
time and/or tissue specificity. Thus, this initiative encourages the submission
of novel approaches to unravel relationships between epigenetic events, diet,
and cancer prevention.
Scope
The common characteristic of the NIH small grant is the provision of limited funding for a short period of time. Examples of the types of projects that NIH ICs support with the R03 mechanism (and that are appropriate for this FOA) include the following:
Examples of Relevant Topics
The following study topics are relevant examples for the development of R03 grant applications in response to this FOA. These examples are not meant to be all-inclusive:
See Section VIII, Other Information - Required Federal
Citations for policies related to this announcement.
Section II. Award
Information
1. Eligible Applicants
1.A. Eligible Institutions
You may submit an application(s) if your
organization has any of the following characteristics:
1.B.
Eligible Individuals
Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with his/her institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
2. Cost Sharing or Matching
This program does not require cost sharing as defined in the current NIH Grants Policy Statement.
3. Other-Special Eligibility Criteria
Investigators wishing to apply for an R03 grant should be aware that not all NIH Institutes and Centers (ICs) accept investigator-initiated R03 applications and that the different NIH ICs may have specific purposes for which they use this funding mechanism. Therefore, all investigators should consult the R03 web site at http://grants.nih.gov/grants/funding/r03.htm as well as the NIH IC staff listed on this web site to determine if an R03 application is appropriate.
Information related to the use of R03 awards by NIH ICs that do not participate in this FOA is also listed on the R03 web site. Additional information about special initiatives involving R03 awards can be found by searching the NIH Guide for Grants and Contracts at http://grants.nih.gov/grants/guide/index.html#search, by examining NIH IC web sites, and by consulting with NIH staff. All investigator-initiated small grant R03 applications described in this FOA will be assigned to the NIH ICs according to standard PHS referral guidelines and specific program interests.
Applicants may submit more
than one application, provided each application is scientifically distinct.
Small grant support may not be used for thesis or dissertation research.
Section
IV. Application and Submission Information
Registration and Instructions for Submission via Grants.gov
To download an Application Package and 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:
Project Directors/Principal Investigators (PDs/PIs) should work with their institutions/organizations to make sure they are registered in the NIH eRA Commons.
Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows:
1) Organization/Institutional Registration in Grants.gov/Get Started.
2) Organization/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
Research & Related Subaward Budget Attachment(s)
Form
Note: While both budget components are included in the SF424
(R&R) forms package, the NIH R03 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 special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.
3.
Submission Dates and Times
See Section IV.3.A for details.
3.A. Submission, Review,
and Anticipated Start Dates
Opening Date:
May 16, 2006
Letters of Intent Receipt Date(s): Not applicable.
Application Submission Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm
AIDS Application Submission Date(s): http://grants1.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 Date(s): 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.
Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two business days to view the application image.
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.
Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing renewal award if such costs: are necessary to conduct the project and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing renewal award.
The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See 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 Guide (MS Word or PDF) are to be followed, with the following requirements for R03 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.
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/index.htm and 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 when making recommendations about funding applications. The effectiveness
of the resource sharing will be evaluated as part of the administrative review
of each non-competing Grant Progress Report
(PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm).
See Section VI.3., Reporting.
Model Organism Sharing Plan: Reviewers are asked to assess the sharing plan in
an administrative note. The sharing plan itself should be discussed after the
application is scored. Whether a sharing plan is reasonable can be determined
by the reviewers on a case-by-case basis, taking into consideration the
organism, the timeline, the applicant's decision to distribute the resource or
deposit it in a repository, and other relevant considerations. For the R03
mechanism, the presence or adequacy of a plan should not enter into the scoring
of the application.
Section
V. Application Review Information
1. Criteria (Update: Enhanced review criteria have been issued for the evaluation of research applications received for potential FY2010 funding and thereafter - see NOT-OD-09-025).
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.
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 R03 small grant is a mechanism for supporting discrete, well-defined projects that realistically can be completed in two years and that require limited levels of funding. Because the research plan is restricted to 10 pages, a small grant application will not have the same level of detail or extensive discussion found in an R01 application. Accordingly, reviewers should evaluate the conceptual framework and general approach to the problem, placing 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 from investigator-generated data. Preliminary data are not required, particularly in applications proposing pilot or feasibility studies.
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 comments, 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. The scientific review group will address and consider each of these criteria in assigning the application's 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 scientific health
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:
Protection of Human Subjects from
Research Risk: The involvement of
human subjects and protections from research risk relating to their
participation in the proposed research will be assessed. See item 6 of the Research
Plan component of the SF424 (R&R)).
Inclusion of Women, Minorities and
Children in Research: The adequacy of
plans to include subjects from both genders, all racial and ethnic groups (and
subgroups), and children as appropriate for the scientific goals of the
research will be assessed. Plans for the recruitment and retention of subjects
will also be evaluated. See item 7 of the Research Plan component of the SF424
(R&R)).
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 SF424 (R&R) will be assessed.
Biohazards: If materials or procedures are proposed that are
potentially hazardous to research personnel and/or the environment, determine
if the proposed protection is adequate.
2.B. Additional Review
Considerations
Budget 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 sharing
research resources plan addressing how unique research resources will be shared
or explain why sharing is not possible.
Program staff will be responsible for the
administrative review of the plan for sharing research resources.
The adequacy of the resources sharing plan will
be considered by Program staff of the funding organization when making
recommendations about funding applications. Program staff may negotiate
modifications of the data and resource sharing plans with the awardee before
recommending funding of an application. The final version of the data and
resource sharing plans negotiated by both will become a condition of the award
of the grant. The effectiveness of the resource sharing will be evaluated as
part of the administrative review of each Non-Competing Grant
Progress Report (PHS 2590). See Section VI.3.
Reporting.
Model Organism Sharing Plan: If applicable, reviewers are asked to assess the sharing plan in an administrative note. The sharing plan itself should be discussed after the application is scored. Whether a sharing plan is reasonable can be determined by the reviewers on a case-by-case basis, taking into consideration the organism, the timeline, the applicant's decision to distribute the resource or deposit it in a repository, and other relevant considerations. For the R03 mechanism, the presence or adequacy of a plan should not enter into the scoring of the application.
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.
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.
The NCI is developing a
policy that will require Clinical Terms of Awards for clinical studies and
trials when they are a component of the proposed research. The policy will
require that studies be monitored commensurate with the degree of potential
risk to study subjects and the complexity of the study. The new policy will be
posted in the NIH Guide within a few weeks. All funded applicants will be
expected to adhere to the new policy.
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:
Sharon A. Ross, Ph.D.
Division of Cancer Prevention
National Cancer Institute
National Institutes of Health
6130
Executive Boulevard, EPN Room 3157, MSC 7328
Bethesda, MD 20892-7328 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery)
Telephone: (301) 594-7547
Fax: (301) 480-3925
E-mail: [email protected]
Vishnudutt
Purohit, Ph.D.
Division
of Metabolism and Health Effects
National
Institute on Alcohol Abuse and Alcoholism
National
Institutes of Health
5635
Fishers Lane, Room 2035, MSC 9304
Bethesda, MD 20892-9304
Telephone:
301-443-2689
Fax:
301-594-0673
Email: [email protected]
Michael
K. May, Ph.D.
National
Institute of Diabetes and Digestive and Kidney Diseases
National
Institutes of Health
6707
Democracy Boulevard, 2 Democracy Plaza
Room 663, MSC 5450
Bethesda, MD 20892-5450 (for U.S. Postal Service express or regular mail)
Bethesda, MD 20817 (for express/courier delivery)
Telephone:
301-594-8884Fax:
301-480-8300
Email: [email protected]
Rebecca
B. Costello, Ph.D., F.A.C.N.
Office of Dietary Supplements
Office of the Director
National
Institutes of Health
6100 Executive Boulevard, Room 3B01, MSC 7517
Bethesda, Maryland 20892-7517
Telephone: (301) 435-2920
Fax: (301) 480-1845
E-mail: [email protected]
2. Peer
Review Contacts:
Not applicable.
3. Financial or
Grants Management Contacts:
Debbie Dunne
Office of Grants Administration
National Cancer Institute
6120 Executive Boulevard, EPN Room 243, MSC 7150
Bethesda, MD 20892-7150 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery)
Telephone: (301) 496-3154
Fax: (301) 402-4918
E-mail: [email protected]
Judy
Fox
Chief, Grants Management Branch
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, Room 3023, MSC 9304
Bethesda, MD 20892-9304
Rockville, MD 20852-1705
Phone: (301)443-4704
Fax: (301)443-3891
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.
Human Subjects Protection:
Federal regulations (45CFR46) require that
applications and proposals involving human subjects must be evaluated with
reference to the risks to the subjects, the adequacy of protection against
these risks, the potential benefits of the research to the subjects and others,
and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).
Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types
of clinical trials, including physiologic toxicity and dose-finding studies
(Phase I); efficacy studies (Phase II); and efficacy, effectiveness, and
comparative trials (Phase III). Monitoring should be commensurate with risk.
The establishment of data and safety monitoring boards (DSMBs) is required for
multi-site clinical trials involving interventions that entail potential risks
to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for
Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).
Sharing Research Data:
Investigators submitting an NIH application seeking
$500,000 or more in direct costs in any single year are expected to include a
plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).
Investigators should seek guidance from their
institutions on issues related to institutional policies and local 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 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.
Inclusion of Women And Minorities in Clinical
Research:
It is the policy of the NIH that women and members of
minority groups and their sub-populations must be included in all NIH-supported
clinical research projects unless a clear and compelling justification is
provided indicating that inclusion is inappropriate with respect to the health
of the subjects or the purpose of the research. This policy results from the
NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All
investigators proposing clinical research should read the "NIH Guidelines
for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the SF424 (R&R); and updated roles and responsibilities
of NIH staff and the extramural community. The policy continues to require for
all NIH-defined Phase III clinical trials that: a) all applications or
proposals and/or protocols must provide a description of plans to conduct
analyses, as appropriate, to address differences by sex/gender and/or
racial/ethnic groups, including subgroups if applicable; and b) investigators
must report annual accrual and progress in conducting analyses, as appropriate,
by sex/gender and/or racial/ethnic group differences.
Inclusion of Children as Participants in Clinical
Research:
The NIH maintains a policy that children (i.e.,
individuals under the age of 21) must be included in all clinical research,
conducted or supported by the NIH, unless there are scientific and ethical
reasons not to include them.
All investigators proposing research involving human
subjects should read the "NIH Policy and Guidelines" on the inclusion
of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).
Required Education on the Protection of Human
Subject Participants:
NIH policy requires education on the protection of
human subject participants for all investigators submitting NIH applications
for research involving human subjects and individuals designated as key
personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can
be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.
Only research using hESC lines that are registered in the NIH Human Embryonic
Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov).
It is the responsibility of the applicant to provide in the project description
and elsewhere in the application as appropriate, the official NIH identifier(s)
for the hESC line(s) to be used in the proposed research. Applications that do
not provide this information will be returned without review.
NIH Public Access
Policy:
NIH-funded investigators are requested to submit to
the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov)
at PubMed Central (PMC) an electronic version of the author's final manuscript
upon acceptance for publication, resulting from research supported in whole or
in part with direct costs from NIH. The author's final manuscript is defined as
the final version accepted for journal publication, and includes all
modifications from the publishing peer review process.
NIH is requesting that authors submit manuscripts
resulting from: (1) currently funded NIH research projects; or (2) previously
supported NIH research projects if they are accepted for publication on or
after May 2, 2005. The NIH Public Access Policy applies to all research grant
and career development award mechanisms, cooperative agreements, contracts,
Institutional and Individual Ruth L. Kirschstein National Research Service
Awards, as well as NIH intramural research studies. The Policy applies to
peer-reviewed, original research publications that have been supported in whole
or in part with direct costs from NIH, but it does not apply to book chapters,
editorials, reviews, or conference proceedings. Publications resulting from
non-NIH-supported research projects should not be submitted.
For more information about the Policy or the
submission process, please visit the NIH Public Access Policy web site at http://PublicAccess.nih.gov/ and
view the Policy or other Resources and Tools including the Authors' Manual (http://publicaccess.nih.gov/publicaccess_manual.htm).
Standards for Privacy of Individually Identifiable
Health Information:
The Department of Health and Human Services (DHHS)
issued final modification to the "Standards for Privacy of Individually
Identifiable Health Information," the "Privacy Rule," on August
14, 2002. The Privacy Rule is a federal regulation under the Health Insurance
Portability and Accountability Act (HIPAA) of 1996 that governs the protection
of individually identifiable health information, and is administered and
enforced by the DHHS Office for Civil Rights (OCR).
Decisions about applicability and implementation of
the Privacy Rule reside with the researcher and his/her institution. The OCR web site (http://www.hhs.gov/ocr/) provides information
on the Privacy Rule, including a complete Regulation Text and a set of decision
tools on "Am I a covered entity?" Information on the impact of the
HIPAA Privacy Rule on NIH processes involving the review, funding, and progress
monitoring of grants, cooperative agreements, and research contracts can be
found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.
URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be
self-contained within specified page limitations. Unless otherwise specified in
an NIH solicitation, Internet addresses (URLs) should not be used to provide
information necessary to the review because reviewers are under no obligation
to view the Internet sites. Furthermore, we caution reviewers that their
anonymity may be compromised when they directly access an Internet site.
Healthy People 2010:
The Public Health Service (PHS) is committed to
achieving the health promotion and disease prevention objectives of
"Healthy People 2010," a PHS-led national activity for setting
priority areas. This FOA is related to one or more of the priority areas.
Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.
Authority and Regulations:
This program is described
in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive
Order 12372 or Health Systems Agency review. Awards are made under the
authorization of Sections 301 and 405 of the Public Health Service Act as
amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost
principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.
The PHS strongly encourages all grant recipients to
provide a smoke-free workplace and discourage the use of all tobacco products.
In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits
smoking in certain facilities (or in some cases, any portion of a facility) in
which regular or routine education, library, day care, health care, or early
childhood development services are provided to children. This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.
Loan Repayment Programs:
NIH encourages applications for educational loan
repayment from qualified health professionals who have made a commitment to
pursue a research career involving clinical, pediatric, contraception,
infertility, and health disparities related areas. The LRP is an important
component of NIH's efforts to recruit and retain the next generation of
researchers by providing the means for developing a research career unfettered
by the burden of student loan debt. Note that an NIH grant is not required for
eligibility and concurrent career award and LRP applications are encouraged.
The periods of career award and LRP award may overlap providing the LRP
recipient with the required commitment of time and effort, as LRP awardees must
commit at least 50 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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