USDA (US Department
of Agriculture) Nutrient
Data Laboratory Home Page http://www.ars.usda.gov/main/site_main.htm?modecode=12354500
USDA
(US Department of Agriculture) Beltsville Human Nutrition Research Center (BHNRC)
http://www.ars.usda.gov/main/site_main.htm?modecode=12-35-00-00
Journal Watch
http://www.jwatch.org/
PubMed
http://www.ncbi.nlm.nih.gov/PubMed/
Virtual Library of Mycology
http://mycology.cornell.edu
Infotrieve
http://www.infotrieve.com/newmedline/search.asp
National Institute of General Medical Sciences
http://nigms.nih.gov/news/Proteinproduction
Detection of Cereal Proteins and DNA Using MS, ELISA, and PCR
http://www.cfsan.fda.gov/~dms/gluthurk/gluhur1.htm
_____________________________________________________________________________________
SAMPLE GRANT PROPOSAL FROM NIH
Executive Summary - This funding opportunity announcement (FOA), issued by the
National Cancer Institute (NCI), is designed to stimulate research efforts aimed at establishing the physiological significance
of dietary components in modulating the tumoricidal cell activity of natural killer (NK) cells for cancer prevention. The
focus of research projects proposed in response to this FOA should be on defining the minimum quantity and duration of exposure
to specific dietary components to modulate tumoricidal cell activity of NK cells for cancer prevention and the underlying
mechanism(s) accounting for this response. Proposed projects must include animal and/or human investigations to be considered
responsive to this announcement. Highly purified populations of immune cells, specific tumor cells such as RMA-S that
lack class I MHC expression, target cell-free system, or single-cell assays may be used to define the molecular basis for
the diet-induced changes in tumoricidal activity. However, the in vitro studies are only to be used to support in
vivo studies and should not constitute the primary focus of the application. Molecular targets for food components may
be examined at the sites of the tumoricidal cell receptors and cancer cell specific ligands, the output of tumoricidal cytokines
(e.g., IFN-g), and the release of lytic granules such as a granulysin, perforin, and serine proteases (granzymes).
- Mechanism
of Support. This FOA will utilize the NIH research project R01 grant mechanism and runs in parallel with an
FOA of identical scientific scope, PA-08-132, that solicits applications for exploratory, pilot projects under
the NIH R21 grant mechanism.
- Funds Available and Anticipated Number of Awards. Awards
issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious
applications.
- Budget
and Project Period. The total project period for an application submitted in response to this funding opportunity
may not exceed 5 years. Applicants for an R01 award are not limited in dollars but need to reflect the actual needs of
the proposed project.
- Application
Research Plan Component Length: The R01 application Research Plan component of the PHS398 (Items 2-5) may not exceed
25 pages, including tables, graphs, figures, diagrams, and charts. See http://grants.nih.gov/grants/funding/funding_program.htm
- Eligible Institutions/Organizations.
Institutions/organizations listed in Section III, 1.A. are eligible to apply.
- Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals
with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/
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.
- Number of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs) may be designated on the application.
- Number of Applications.
Applicants may submit more than one application, provided each application is scientifically
distinct.
- Resubmissions.
Applicants may submit a resubmission application, but such application must include an
Introduction addressing the previous peer review critique (Summary Statement).
- Renewals. Applications can be renewed by competing for additional project periods.
- Application Materials.
See Section IV.1 for application materials.
- General Information.
For general information on SF424 (R&R) Application and Electronic Submission, see these Web
sites:
- Hearing Impaired. Telecommunications
for the hearing impaired are available at: TTY 301-451-0088.
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. Receipt,
Review, and Anticipated Start Dates
1. Letter of Intent
B.
Submitting an Application Electronically to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements and Information
Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional
Review Considerations
C. Resource Sharing Plan(s)
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 Contacts
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
This
NCI-sponsored Funding Opportunity Announcement (FOA) promotes research to characterize the significance of dietary components
in regulating the tumoricidal activity of natural killer (NK) cells for cancer prevention. Specifically, this FOA encourages
studies that can establish the physiological significance of dietary components in modulating the tumoricidal activity of
NK cells. Research projects proposed in response to this FOA should focus on defining the minimum quantity and duration of
exposure to specific dietary components to modulate tumoricidal activity of NK cells for cancer prevention and the underlying
mechanism(s) accounting for this response.
Proposed projects must include animal and/or human investigations
to be considered responsive to this announcement. In vitro models can be used only to support in vivo studies,
and therefore, should not constitute the primary focus of the application. Molecular targets for food components may be examined
at the sites of: 1) the tumoricidal cell receptors and cancer cell specific ligands; 2) the release of tumoricidal cytokines
such as IFN-g; and 3) the release of lytic granules such as granulysin, perforin, and serine proteases (granzymes).
Using the NIH Research Project Grant (R01) funding mechanism, this FOA focuses on discrete, specified, circumscribed
projects based upon strong preliminary data.
Related Funding Opportunity: Investigators, who
are interested in proposing exploratory and developmental research projects, should submit applications in response to the
partner FOA of identical scientific scope (PA-08-132), which uses the NIH R21 grant mechanism.
Background
The growth and spread of cancer depend not only on the biological characteristics of the tumor per se but also on
the host responses. NK cells represent one significant venue for influencing tumor growth and metastasis. NK cells are large
granular lymphocytes without B or T cell characteristics; these cells are highly effective killers of both tumor cells and
virally infected cells without the need for prior sensitization or recognition of a specific antigen. An important characteristic
of cancer is that the disease can overcome the surveillance of the immune system. One possible explanation for this resistance
(to immune surveillance) arises from the ability of tumor cells to inactivate the tumoricidal activity of host’s NK
cells, thereby evading this first-line immune defense mechanism. Furthermore, inappropriate changes in microenvironment caused
by treatment with various drugs, such as interferons (IFNs), and Interleukin-2 (IL-2) that can up-regulate NK cell activity,
result in their attacking both “self” and “non-self” cells. Thus, it is extremely important to understand
the early stage(s) of tumor-host interactions, and redirect these events from a pro-tumor to an anti-tumor state. Diet may
represent a subtle approach to regulating NK cells without losing their self-tolerance mechanism.
Several lines
of preliminary evidence suggest that a number of bioactive food components can induce tumor cell death, possibly by enhancing
NK cell activity. For example, extracts of the Maitake- (Grifola frondosa) and Brazilian sun- mushrooms (Agaricus Blazei)
can enhance the cytolytic activity of NK cells in tumor-bearing mice. Likewise, dietary supplementation with 250 mg vitamin
E/day (for 2 weeks) can enhance NK cell cytolytic activity in advanced colorectal cancer patients. In addition, the supplementation
of vitamin E (administered at 100 mg/day for 8 weeks) restored NK cell activity in a 16 month-old boy with Shwachman-Diamond
syndrome that is classically associated with a persistent reduction in NK cytolytic activity. However, these preliminary findings
and rare cases are only suggestive of the involvement of dietary components in regulation of the tumoricidal activity of NK
cells. The precise role(s) by which these and other dietary components influence NK cells, such as modulation of receptor-ligand
interactions and/or the release of cytokines and lytic enzymes, remains largely unknown.
Interaction of
bioactive food components with NK cell receptors and their ligands. Both experimental and clinical data indicate
an important role for NK cells in early neoplastic development, possibly by either responding to specific ligands generated
by cancer cells, or to various types of extracellular or cell-associated proteinases. NK cells are known to exert their activity
through a diverse repertoire of activating (e.g., NKG2 receptor family) and inhibitory (e.g., killer immunoglobulin-like receptor
[KIR] family) receptors that recognize specific ligands on the surface of target cells. Many of the KIRs recognize major histocompatibility
(MHC) class I molecules, which in humans are human leukocyte antigen (HLA) class I molecules. The KIRs provide protection
for cells that express normal levels of MHC class1 molecules on their surface. In general, the co-ligation of activating and
inhibitory receptors results in a net negative (i.e., no cytotoxicity) reaction. In contrast, the down-regulation of MHC class
I in cancer, together with expression of specific ligands for activating receptors such as MICA, MICB, or UL16-binding proteins,
enhances the sensitivity of target cells to NK cell-mediated cytotoxicity.
There is some evidence to suggest that certain dietary components may modulate the NK cell activity
in response to antigen stimuli. For example, when C57BL/6J mice were maintained for eight weeks on Selenium (Se)-deficient
(~0.02 ppm), Se-normal (~0.20 ppm), or Se-supplemented (~2.00 ppm) diets, lymphocyte activity was differentially modulated;
lymphocytes isolated from animals maintained on the Se-supplemented diets had an enhanced ability to destroy tumor cells compared
with lymphocytes from animals that were maintained on either a normal or Se-deficient diet. While these studies support the
general concept that specific dietary components can modify tumoricidal activity of NK cells, the evidence largely remains
indirect. Therefore, the underlying mechanisms deserve additional study in order to develop and optimize future intervention
strategies.
Influence of bioactive food components on cytokine release from NK cells. Circulating
NK cells are mature, as opposed to dendritic cells, which only mature during inflammation or infection. During early
onset inflammation, immature dendritic cells secrete a variety of cytokines including tumor necrosis factor alpha (TNF-α),
IL-2, and IL-12. These cytokines can induce a rapid expression of IFN-g and subsequently enhance the intrinsic cytolytic
activity of NK cells. However, the response is complex since a T-Helper 2 (TH2) cytokine such as IL-4, which is generally
viewed as an antagonist of IFN-
expression (in T cells), can induce signal transducer and activator of transcription 6 (STAT6)-dependent IFN-g secretion
by NK cells. While some evidence suggests that specific bioactive food components (such as those derived from fermentable
fibers and mushrooms) can modulate the release of various cytokines, it remains unclear whether these changes accompany a
proportional alteration in the NK cell activity. NK cells, which can lyse tumor cells, provide antigenic cellular debris for
mature dendritic cells to present to T cells; in later stages, NK cells terminate the process by lysing the dendritic cells
and halting their ability for antigen presentation.
Dietary modulation of release of lytic granules from NK cells. The lysosomal
release of cytotoxic granules from NK cells, including two membrane-perturbing proteins such as perforin and granulysin, and
a family of serine proteases (also known as granzymes), constitutes the main pathway for the immune system-mediated elimination
of tumor cells. A number of studies indicate that dietary habits, including caloric restriction and alcohol consumption, may
influence the cytolytic activity of NK cells by down-regulating the release, activity, and expression of perforin and granular
proteases. Nevertheless, these observations need to be further characterized in mechanistic studies to establish a link between
dietary modulation and cancer prevention.
Models for examining dietary components on NK tumoricidal activity. NK
cells, once activated, initiate the tumoricidal process through the release of both lytic granules and serine proteases (granzymes)
or tumor-suppressive cytokines such as IFN-g, to mediate transformed cell death. Support for these findings comes from the
inability of cytotoxic T lymphocytes (CTLs) to kill their target cells in either perforin-null or ashen mice that possess
impaired granule pathway. Recently, genetically modified mouse cancer models have been extensively used for analyzing the
occurrence of molecular events during the tumoricidal process. Analogous studies have also been conducted in humans with diseases
caused by defects in tumor cell killing. Since a number of dietary components may influence NK cell tumoricidal activity,
it would be prudent to use various models to establish the physiological significance of dietary components as either cancer
protectants or modulators of cancer risk.
An example of the usefulness of the defined mouse model systems comes from studies using a recombination
activating gene 2-deficient (RAG-2 -/-) mice. These mice fail to produce mature lymphocytes, which are critical for generating
active forms of perforin and IFN-g. Consequently, RAG-2 -/- mice are highly susceptible to spontaneous development of adenocarcinomas
in colon and lungs. Tumor growth in these genetically engineered mice was shown to be suppressed in response to dietary supplementation
with Brazilian sun-mushrooms (Agaricus Blazei). A. blazei is an edible mushroom with anticancer activity native to Brazil;
oral intake of A. blazei can enhance NK cell activation through IL-12-mediated IFN-g production.
Another mouse model includes deficiencies in STAT1 gene that is critical
for the function of IFN-g . Double knockout animals of STAT1 -/- and RAG-2 -/- not only exhibit early onset of malignancy
in colon and lung, but also demonstrate an exaggerated incidence of mammary cancers. In addition, mice with deficiencies in
a subunit of IFN receptor expression (IFNAR -/-) were successfully used to demonstrate that endogenous Type 1 IFN is critical
for controlling NK cell-mediated anti-tumor responses. These findings suggest that both IFN-g and perforin are critical in
regulating some solid tumors. Therefore, the use of these models for determining the influence of bioactive food components
on NK cell activity warrants further studies, given the literature evidence that several food items can modulate cancer risk,
especially in cancers of the colon, lung, prostate, and mammary tissue.
Research Objectives and Scope of this FOA
The goal of this FOA is to encourage studies that can establish the
physiological significance of dietary components in modulating the tumoricidal activity of NK cells for cancer prevention.
The focus of the research should be on defining the minimum quantity and duration of exposure to specific dietary components
to modulate tumoricidal activity of NK cells for cancer prevention and the underlying mechanism(s) accounting for this response.
Both animal- and human- based investigations are responsive to this FOA. Highly purified populations of immune cells,
specific tumor cell lines, target cell-free systems, or single-cell assays may be used to define the molecular bases for diet-induced
changes in NK tumoricidal activity. However, in vitro information can be used only to support in vivo
studies, and therefore, should not constitute the primary focus of the application. Molecular targets for food components
may be examined at the sites of: 1) the tumoricidal cell receptors and cancer cell specific ligands; 2) the release of tumoricidal
cytokines such as IFN-g; and 3) the release of lytic granules such as granulysin, perforin, and serine proteases (granzymes).
A variety of technologies including
those of genomics, proteomics, and metabolomics can be used to identify and characterize the molecular targets for dietary
components, as well as the methods for monitoring tumoricidal activity of NK cells, which correlate with cancer prevention.
The use of transgenic and/or conditional knockout mouse models that are associated with alterations in NK cell tumoricidal
function is encouraged; several of these mouse models are available through the Mouse Models for Human Cancer Consortium (MMHCC). The efficient utilization of molecular resources such as gene,
protein, and metabolome databases may be used to expedite the proposed research studies. Bioinformatics-based approaches may
also be necessary to identify the complex patterns of alterations in genes, proteins, and metabolites, which can generate
unique fingerprints for any given dietary treatments. Applicants are encouraged to use research information resources available
at the NCI Center for Bioinformatics (NCICB).
Research topics that are relevant to this FOA include, but are not limited to, the
following examples:
- Define if the
exposure to varying quantities of mushroom-derived β-glucans and vitamin E corresponds to changes in an activation (e.g.
NKG2D) or inhibition (e.g. KIRs) of NK cell receptors and accompanies proportional change(s) in the removal of transformed
cells
- Evaluate if NK cells from MHC1-deficient
mice and humans respond differently to specific bioactive food components and thus examine the importance of MHC1 in target
recognition for pre-neoplastic lesions
- Evaluate
the response to garlic extracts on secretion of specific cytokines (such as TNF-a, IL-6, IL-10, and IL-13), and
its relationship to tumoricidal activity of NK cells following exposure to pathogens
- Evaluate the influence of time and duration of exposure to dietary phytic acids on the
release of lytic enzymes (such as granulysin or perforin) from NK cells derived from cancer cells
- Examine if dietary curcumin can influence interactions between NK and regulatory
T cells, and whether these interactions can partially reverse tumor exosome-mediated inhibition of NK cell activation in
vivo
- Compare the redistribution of tumoricidal
NK cells from bone marrow to blood as a function of the type and quantity of dietary lipids consumed.
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 research project (R01) grant award mechanism. The Project Director/Principal
Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.
This FOA uses “Just-in-Time”
information concepts (see SF424 (R&R) Application Guide). It also uses the modular as well
as the non-modular budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, a U.S.
organization submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities
and Administrative [F&A] costs) must use the PHS398 Modular Budget component.
U.S.
applicants requesting more than $250,000 in annual direct costs and all Foreign applicants must complete and submit budget
requests using the Research & Related (R&R) Budget component.
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 NCI provide support for this program,
awards pursuant to this funding opportunity are contingent upon the availability of funds.
Facilities and Administrative
(F&A) costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response
to this FOA.
Section III. Eligibility Information
1. Eligible Applicants
1.A. Eligible Institutions
The
following organizations/institutions are eligible to apply:
- Public/State Controlled Institutions of Higher Education;
- Private Institutions of Higher Education;
- Nonprofits
with 501(c)(3) IRS Status (Other than Institutions of Higher Education);
- Nonprofits without 501(c)(3) IRS Status (Other than Institutions of
Higher Education);
- Small Businesses;
- For-Profit Organizations (Other than Small Businesses);
- State Governments;
- U.S.
Territories or Possessions;
- Regional Organizations;
- Non-domestic (non-U.S.) Entities
(Foreign Organizations); and
- Eligible Agencies of the Federal Government.
1.B. Eligible Individuals
Any individual(s)
with the skills, knowledge, and resources necessary to carry out the proposed research as the 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.
More than one PD/PI (i.e., multiple
PDs/PIs), may be designated on the application for projects that require a “team science” approach and therefore
clearly do not fit the single-PD/PI model. Additional information on the implementation plans and policies and
procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered
in the NIH electronic Research Administration (eRA) Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).
The decision of whether to apply
for a grant with a single PD/PI or multiple PDs/PIs grant is the responsibility of the investigators and applicant organizations
and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require
additional information, as outlined in the instructions below. The NIH review criteria for approach, investigators, and environment
have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. When considering the multiple
PD/PI option, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills
and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application.
Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually
and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating
organization, for the proper conduct of the project or program, including the submission of required reports. For further
information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.
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
Applicants may submit resubmission applications, but any such application must include an Introduction
addressing issues raised in the previous critique
(Summary Statement).
Applicants may submit renewal applications.
Applicants
may submit more than one application, provided that each application is scientifically distinct.
Section IV. Application and Submission Information
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, use the “Apply for Grant Electronically”
button in this FOA or 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 NIH eRA Commons.
Several additional separate actions are required before an applicant
small business concern (SBC) can submit an electronic application, as follows:
1) Organizational/Institutional Registration in Grants.gov/Get Registered
- Your organization will need to obtain a Data Universal Number System (DUNS) number and register with the Central Contractor Registration (CCR) as part of the Grants.gov registration process.
- If your organization does not have a Taxpayer Identification Number
(TIN) or Employer Identification Number (EIN), allow for extra time. A valid TIN or EIN is necessary for CCR registration.
- The CCR also validates the EIN against Internal
Revenue Service records, a step that will take an additional 1 to 2 business days.
- Direct questions regarding Grants.gov registration to:
Grants.gov Customer Support
Contact Center Phone: 800-518-4726
Business Hours:
M-F 7:00 a.m. - 9:00 p.m. Eastern Time
Email: support@grants.gov
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.
- The individual(s) designated as PDs/PIs
on the application must be registered also in the NIH eRA Commons. In the case of multiple PDs/PIs, all PDs/PIs must
be registered and be assigned the PI role in the eRA Commons prior to the submission of the application.
- Each PD/PI must hold a PD/PI account in the Commons.
Applicants should not share a Commons account for both an Authorized Organization Representative/Signing Official (AOR/SO)
role and a PD/PI role; however, if they have both a PD/PI role and an NIH Internet Assisted Review (IAR) role, both roles
should exist under one Commons account.
- When multiple
PDs/PIs are proposed, all PDs/PIs at the applicant organization must be affiliated with that organization. PDs/PIs located
at another institution need not be affiliated with the applicant organization, but must be affiliated with their own organization
to be able to access the Commons.
- This registration/affiliation
must be done by the AOR/SO or his/her designee who is already registered in the Commons.
Both the PDs/PI(s) and AOR/SO need separate accounts in the NIH eRA
Commons since both are authorized to view the application image.
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 organization/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 the 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: 301-435-0714; Email: GrantsInfo@nih.gov.
Telecommunications for the hearing impaired: TTY 301-451-0088.
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 for this FOA through Grants.gov/Apply.
The
SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. Some fields within
the SF424 (R&R) application components, 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 “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”
The SF424 (R&R) application has several components. Some components are required,
others are optional. The forms package associated with this FOA in Grants.gov/APPLY includes all applicable components, required and optional. A completed application in response to this FOA includes the
data in 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
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget or
Research & Related Budget, as appropriate (See Section IV.6., “Special Instructions,” regarding appropriate
required budget component.)
Optional Components:
PHS398 Cover Letter
File
Research & Related Subaward Budget Attachment(s) Form
Foreign
Organizations (Non-Domestic [non-U.S.] Entities)
NIH policies concerning grants to Foreign
(non-U.S.) organizations can be found in the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.
Applications
from Foreign organizations must:
- Request budgets in U.S. dollars;
- Prepare
detailed budgets for all applications (that is, complete the Research & Related Budget component of the SF424 (R&R)
application forms – not the PHS398 Modular Budget component)(see NOT-OD-06-096);
- Not include any charge-back of customs and import fees;
- Comply with
the format specifications, which are based upon a standard U.S. paper size of 8.5” x 11” within each PDF;
- If
appropriate, request funds for up to 8% administrative costs (excluding equipment) (see NOT-OD-01-028, March 29, 2001);
- Comply with Federal/NIH policies on human
subjects, animals, and biohazards; and
- Comply with Federal/NIH biosafety and biosecurity regulations (see Section VI.2., “Administrative
and National Policy Requirements”).
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 (U.S.) or that augment existing U.S. resources.
SPECIAL INSTRUCTIONS
Applications with Multiple PDs/PIs
When multiple PDs/PIs are proposed, NIH requires
one PD/PI to be designated as the "Contact” PI, who will be responsible for all communication between the PDs/PIs
and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project.
The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other
special roles or responsibilities within the project team beyond those mentioned above.
Information for the Contact PD/PI
should be entered in Item 15 of the SF424 (R&R) Cover component. All other PDs/PIs should be listed in the Research
& Related Senior/Key Person component and assigned the project role of “PD/PI.” Please remember that
all PDs/PIs must be registered in the eRA Commons prior to application submission. The
Commons ID of each PD/PI must be included in the “Credential” field of the Research & Related Senior/Key Person
component. Failure to include this data field will cause the application to be rejected.
All projects proposing Multiple
PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.
Multiple
PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of
the research plan, entitled “Multiple PD/PI Leadership Plan” [Section 14 of the Research Plan Component in the
SF424 (R&R)], must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance
and organizational structure of the leadership team and the research project should be described, and should include communication
plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative,
technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.
If budget allocation is planned, the distribution of resources to specific components of the project or the
individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be
reflected in a footnote on the Notice of Award (NoA).
Applications Involving a Single Institution
When all PDs/PIs are within a single institution, follow the instructions
contained in the SF424 (R&R) Application Guide.
Applications Involving Multiple Institutions
When multiple institutions are involved, one
institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract
to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget
using the Research & Related (R&R) Budget component. All other institutions should have their individual budgets
attached separately to the Research & Related Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R)
Application Guide for further instruction regarding the use of the subaward budget form.
When submitting a modular budget, the prime
institution completes the PHS398 Modular Budget component only. Information concerning the consortium/subcontract budget
is provided in the budget justification. Separate budgets for each consortium/subcontract grantee are not required when using
the Modular budget format. See Section 5.4 of the Application Guide for further instruction regarding the use of the PHS398
Modular Budget component.
3. Submission Dates and Times
See Section IV.3.A. for details.
3.A. Submission, Review, and Anticipated Start Dates
Opening Date: April
15, 2008 (earliest date an application may be submitted to Grants.gov).
Application Due Dates:
Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm
AIDS Application Due Dates: Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#AIDS
Peer Review Dates:
Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council Review Dates: Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest Anticipated Start Dates: Standard dates
apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
3.A.1.
Letter of Intent
A letter of intent is not required for the funding opportunity.
3.B. Submitting an Application Electronically
to the NIH
To submit an application in response to this FOA, applicants should
access this FOA via http://www.grants.gov/applicants/apply_for_grants.jsp and follow Steps 1-4. Note: Applications must only
be submitted electronically. PAPER APPLICATIONS WILL NOT BE ACCEPTED.
In order to expedite the review, applicants are requested to notify
the NCI Referral Office by email (ncirefof@dea.nci.nih.gov ) when the application has been submitted. Please include the FOA number and title,
PD/PI name, and title of the application.
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 due date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the due 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 weekdays (Monday – Friday, excluding Federal holidays) to view the application image to determine
if any further action is necessary.
- If
everything is acceptable, no further action is necessary. The application will automatically move forward to the Division
of Receipt and Referral in the NIH Center for Scientific Review (CSR) for processing after 2 weekdays, excluding Federal holidays.
- Prior to the submission deadline,
the AOR/SO can “Reject” the assembled application and submit a changed/corrected application within the 2-day
viewing window. This option should be used if it is determined that some part of the application was lost or did not transfer
correctly during the submission process, the AOR/SO will have the option to “Reject” the application and submit
a Changed/Corrected application. In these cases, please contact the eRA Help Desk to ensure
that the issues are addressed and corrected. Once rejected, applicants should follow the instructions for correcting errors
in Section 2.12, including the requirement for cover letters on late applications. The “Reject”
feature should also be used if you determine that warnings are applicable to your application and need to be addressed now.
Remember, warnings do not stop further application processing. If an application submission results in warnings (but no errors),
it will automatically move forward after 2 business days if no action is taken. Some warnings may need to be
addressed later in the process.
- If the 2-day window falls after the submission deadline, the AOR/SO will have the option to “Reject”
the application if, due to an eRA Commons or Grants.gov system issue, the application does not correctly reflect the submitted
application package (e.g., some part of the application was lost or didn’t transfer correctly during the submission
process). The AOR/SO should first contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine
the best course of action. NIH will not penalize the applicant for an eRA Commons or Grants.gov system issue.
- If the AOR/SO chooses to “Reject” the image after the submission deadline for a reason
other than an eRA Commons or Grants.gov system failure, a changed/corrected application still can be submitted, but it will
be subject to the NIH late policy guidelines and may not be accepted. The reason for this delay
should be explained in the cover letter attachment.
- Both the
AOR/SO and PD/PI will receive e-mail notifications when the application is rejected or the application automatically moves
forward in the process after 2 days.
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. The submitting AOR/SO receives the Grants.gov acknowledgments. The AOR/SO and the PI receive Commons acknowledgments. Information
related to the assignment of an application to a Scientific Review Group is also in the Commons.
Note: Since email can be unreliable,
it is the responsibility of the applicant to check periodically on the application status 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. However,
the NIH will accept a resubmission application, but such application must include an Introduction addressing the critique
from the previous review.
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: 1) are necessary to conduct
the project, and 2) 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 and Information
PD/PI Credential (e.g., Agency Login)
The NIH requires
the PD(s)/PI(s) 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.
Organizational DUNS
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 “Frequently
Asked Questions – Application Guide, Electronic Submission of Grant Applications.”
PHS398 Research Plan Component Sections
Page limitations of the PHS398 Research Plan
component must be followed as outlined in the SF424 (R&R) Application Guide. While each section of the Research Plan component
needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component 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.
All application
instructions outlined in the SF424 (R&R) Application Guide are to be followed, incorporating "Just-in-Time"
information concepts.
Specific Instructions for Applications Requesting $500,000 (direct costs) or More per Year
Applicants requesting $500,000 or more in direct costs for any year (excluding consortium F&A
costs) must carry out the following steps:
1) Contact the NIH IC program staff
person(s) at least 6 weeks before submitting the application, i.e., as plans are being developed for the study;
2) Obtain agreement from the IC
staff that the IC will accept the application for consideration for award; and
3)
Include a cover letter with the application that identifies the staff member and IC that agreed to accept assignment of the
application.
This
policy applies to all new, renewal, revision, and resubmission applications. See NOT-OD-02-004, October 16, 2001.
Appendix Materials
Applicants must follow the specific instructions on
Appendix materials as described in the SF424 (R&R) Application Guide (See http://grants.nih.gov/grants/funding/424/index.htm).
Do
not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not comply
with the required page limitations may be delayed in the review process.
Resource Sharing Plan(s) NIH considers the sharing of unique research resources developed
through NIH-sponsored research an important means to enhance the value and further the advancement of the research. When resources
have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that
they be made readily available for research purposes to qualified individuals within the scientific community. If
the final data/resources are not amenable to sharing, this must be explained in the Resource Sharing section of the application
(see http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm).
(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to
include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact (see Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.)
(b) Sharing Model Organisms: Regardless of the amount requested, all applications where
the development of model organisms is anticipated are expected to include a description of a specific
plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing
is restricted or not possible. See Sharing Model Organisms Policy and NIH Guide NOT-OD-04-042.
(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested,
applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS
data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission
to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the
entire genome that is designed to identify genetic associations with observable traits (e.g., blood pressure or weight) or
the presence or absence of a disease or condition. For further information, see Policy for Sharing of Data Obtained in NIH
Supported or Conducted Genome-Wide Association Studies (go to NOT-OD-07-088 and http://grants.nih.gov/grants/gwas/.)
Foreign Applications (i.e., those from Non-Domestic [non-U.S.] Entities)
Indicate how the
proposed project has specific relevance to the mission and objectives of the NIH/IC and has the potential for significantly
advancing the health sciences in the United States.
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
A
pplications submitted for this funding opportunity will be assigned on the basis of established
PHS referral guidelines to the ICs for funding consideration.
As part of the scientific peer review, all
applications will:
- Undergo
a selection process in which only those applications deemed to have the highest scientific and technical merit, generally
the top half of applications under review, will be discussed and assigned a priority score;
- Receive a written critique; and
- Receive a second level of review by the
appropriate national advisory council or board.
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:
- Scientific and technical merit of the proposed project as determined by scientific peer review;
- Availability of funds; and
- Relevance of the proposed project to program
priorities.
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, and weighted 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 meritorious 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? For applications designating multiple PDs/PIs, is the leadership approach, including the designated roles and
responsibilities, governance, and organizational structure, consistent with and justified by the aims of the project and the
expertise of each of the PDs/PIs?
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 or methodologies,
tools, or technologies for this area?
Investigators: Are the PD/PIs
and other key personnel appropriately trained and well suited to carry out this work? Is the work proposed appropriate to
the experience level(s) of the principal investigator(s) and other researchers? Do the PD/PIs and investigative team bring
complementary and integrated expertise to the project (if applicable)?
Environment:
Do(es) the scientific environment(s) 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(s), 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 rating:
Resubmission Applications: Are the responses to comments
from the previous scientific review group adequate? Are the improvements in the resubmission application appropriate?
Protection
of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation
in the proposed research will be assessed. See the “Human Subjects Sections” of the PHS398 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 the “Human Subjects Sections” of the PHS398 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
adequacy of the plans for their care and use will be assessed. See the “Other Research Plan Sections” of the PHS398
Research Plan component of the SF424 (R&R).
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. The priority score
should not be affected by the evaluation of the budget.
Applications from Foreign Organizations: Whether the project
presents 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 will be assessed.
2.C. Resource Sharing Plan(s) When relevant, reviewers will be instructed to comment on the reasonableness
of the following Resource Sharing Plans, or the rationale for not sharing the following types of resources. However, reviewers
will not factor the proposed resource sharing plan(s) into the determination of scientific merit or priority score, unless
noted otherwise in the FOA. Program staff within the IC will be responsible for monitoring the resource sharing.
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 email 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 Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.
A
final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a
recipient changes institutions or when an award is terminated.
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 (program), peer review, and
financial or grants management issues.
1. Scientific/Research Contact(s):
Young S. Kim, Ph.D.
Division
of Cancer Prevention
National Cancer Institute
6130 Executive Boulevard, EPN Room 3156, MSC 7328
Bethesda,
MD 20892-7328 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone:
(301) 496-0126
Fax: (301) 480-3925
E-mail: yk47s@nih.gov
T. Kevin Howcroft, Ph.D.
Cancer Immunology and Hematology Branch
Division of Cancer Biology
National Cancer Institute
6130 Executive Boulevard, EPN Room 5060, MSC 7388
Bethesda, MD 20892-7388 (for
U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-7815
Fax: (301) 480-2844
E-mail: Howcrofk@mail.nih.gov
2. Peer Review Contact(s):
Not applicable.
3. Financial/Grants Management Contact(s):
Funmi Elesimogun
Office
of Grants Administration
National Cancer Institute
6120 Executive Boulevard, EPS 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) 496-7245
Fax: (301) 496-8601
E-mail: elesinmf@mail.nih.gov
Section VIII. Other Information
Required Federal Citations
Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with
PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.
Human Subjects Protection:
Federal regulations
(45 CFR 46) 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).
Policy for Genome-Wide Association Studies (GWAS):
NIH
is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health
and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is
defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations
with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications,
regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission
of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository
is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained
in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/.
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. Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal 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.
Access to Research Data through the Freedom of Information
Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised
to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are:
(1) first produced in a project that is supported in whole or in part with Federal funds; and (2) cited publicly and officially
by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through
FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections
for the data and manage the distribution for an indefinite period of time. If so, the application should include a description
of the archiving plan in the study design and include information about this in the budget justification section of the application.
In addition, applicants should think about how to structure informed consent statements and other human subjects procedures
given the potential for wider use of data collected under this award.
Inclusion of Women And
Minorities in Clinical Research:
It is the policy of the NIH that women and
members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless
a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of
the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of
Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women
and Minorities as Subjects in Clinical Research” (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories
in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent
with the SF424 (R&R) application; 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 Requirement:
In accordance with the NIH Public Access Policy, investigators funded by the NIH
must submit or have submitted for them to the National Library of Medicine’s PubMed Central (see http://www.pubmedcentral.nih.gov/), an electronic version of their final, peer-reviewed manuscripts
upon acceptance for publication, to be made publicly available no later than 12 months after the official date of publication.
The NIH Public Access Policy is available at (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html). For more information, see the Public Access webpage at http://publicaccess.nih.gov/.
Standards for Privacy of Individually Identifiable
Health Information:
The Department of Health and Human Services (HHS) 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 HHS Office for Civil Rights (OCR).
Decisions about applicability and implementation
of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I
a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding,
and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.
URLs in NIH Grant Applications or Appendices:
All applications and proposals
for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress
report, Internet addresses (URLs) or PubMed Central (PMC) submission identification numbers must be used for publicly accessible
on-line journal articles. Publicly accessible on-line journal articles or PMC articles/manuscripts accepted for publication
that are directly relevant to the project may be included only as URLs or PMC submission
identification numbers accompanying the full reference in either the Bibliography & References Cited section,
the Progress Report Publication List section, or the Biographical Sketch section of the NIH grant application. A URL or PMC
submission identification number citation may be repeated in each of these sections as appropriate. There is no limit to the
number of URLs or PMC submission identification numbers that can be cited.
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 Part 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 PHS strongly encourages all
grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law
103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility)
in which regular or routine education, library, day care, health care, or early childhood development services are provided
to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American
people.
Loan Repayment Programs:
NIH
encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue
a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP
is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means
for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for
eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may
overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least
50% of their time (at least 20 hours per week based on a 40 hour week) for 2 years to the research. For further information,
please see http://www.lrp.nih.gov/.