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 Aging (NIA), (http://www.nia.nih.gov/)
Title: Stem Cells and Cancer (R21)
Announcement Type
This is a reissue of PA-05-086, which was previously
released April 12, 2005.
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 applicants are highly encouraged to start the process at least 4 weeks prior to the grant submission date. See Section IV.
Two steps are required for on time submission:
1) The application must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the submission/receipt date (see Key Dates below); and
2) Applicants must complete a verification step in the eRA Commons within 2 business days of notification from NIH. Note: Since e-mail can be unreliable, it is the responsibility of the applicant to periodically check on their application status in the Commons.
Program Announcement (PA) Number: PA-06-282
Catalog of Federal Domestic Assistance Number(s)
93.396, 93.866
Key
Dates
Release/Posted Date: March 28, 2006
Opening Date: May 2 , 2006 (earliest date an application may be
submitted to Grants.gov).
Letters of Intent Receipt Date(s): Not
applicable.
Application Submission
Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
AIDS Application Receipt Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#AIDS.
Peer Review Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
Council Review Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
Earliest Anticipated Start Date: http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
Additional Information To Be Available Date
(URL Activation Date): Not applicable.
Expiration Date: May 2, 2008 (now May 8, 2008 per NOT-OD-07-093)
Due Dates for E.O. 12372
Not Applicable.
Additional Overview
Content
Executive Summary
Stem
cells play a crucial role in all aspects of biology from the development of
early embryos to the repair and maintenance of adult tissues. Embryonic stem
cells can give rise to all the tissue types in the adult organism. Adult stem
cells residing in a number of adult tissues are important to tissue self
renewal and repair. These somatic stem cells are unique among adult cells, in
that they can undergo self renewal divisions, although they have a limited
capacity for multi-lineage differentiation. Examples of such stem cells are the
hematopoietic stem cells that are crucial to the success of bone marrow
transplantation in the therapy of cancer.
Recently, a new type of stem cell has been isolated and characterized from a
number of solid and liquid tumors. These tumor stem cells are a rare population
of tumor cells that can reconstitute a new tumor with all the cell types
represented in the tumor of origin. These tumor stem cells are putatively
responsible for the transplantability and metastatic properties of tumors. The
cells are capable of self renewal and asymmetric cell division, as are normal
adult and embryonic stem cells. The isolation of such tumor stem cells is
important to more completely understand the progression of malignant disease,
as well as to the development of improved specific therapies for cancer. Thus
far, tumor stem cells have been isolated from only a small number of
histological tumor types, and stem cells from a greater spectrum of tumors must
be isolated and biologically characterized. In addition, more research is
needed to understand the genetic and biochemical regulatory mechanisms that
control the self-renewal phenotype, asymmetric cell division, and the role of
the stem cell niche in regulating the biological properties of both normal and
tumor stem cells.
The National Cancer Institute is interested in stimulating research on all
aspects of stem cell biology, including research into the molecular and
biochemical regulation of embryonic and adult stem cell behavior. We anticipate
that the results of such research will ultimately improve the specificity and
long-term effectiveness of cancer therapy, through the targeting of those cells
most responsible for disease progression and metastasis. The Research Objectives
section of this announcement will focus on the most recent research on tumor
stem cells, because of the importance of these stem cells to understanding
tumor biology. However, it should be emphasized that the purpose of this
announcement is to encourage research on all aspects of stem cell biology.
The clonal nature of most malignant
tumors is well established. Experiments spanning several decades have shown,
however, that as many as 1 million murine or human tumor cells are required to
transplant a new tumor from an existing one. Two theories have been developed
to account for the observation that apparently not every tumor cell is a tumor
initiating cell (T-IC). The stochastic theory predicts that every tumor cell
can form an entirely new tumor; however, entry into the cell cycle is a
stochastic event with low probability. Alternatively, tumor cells may exist in
a hierarchical state in which only a small number of cells possess tumor
initiating potential. If the stochastic model is correct then tumor cells are
biologically homogeneous and genetic or epigenetic programs that allow for
tumorigenesis are operative in the majority of cells that comprise a tumor. The
hierarchical model, however, predicts the tumor cells possess a functional
heterogeneity and that quantitatively the cells capable of tumorigenesis are a
relatively minor population among the bulk of tumor cells.
Recent data from both hematologic malignancies and solid tumors have suggested
that there are only minor populations of cells in each malignancy that are
capable of tumor initiation. These T-ICs have the functional properties of
tumor stem cells. They appear to be capable of asymmetric division and self
renewal, are only a minor faction among the bulk of more differentiated cells
in the tumor, and can reconstitute all the cell types in the tumor of origin.
Currently, tumor stem cells have been isolated and characterized in several
hematologic malignancies and some solid tumors. One of the first tumors in
which a stem cell was identified was acute myeloid leukemia (AML). In this
disease, the frequency of the leukemic stem cell (LSC) was approximately 1 per
million AML blasts, establishing that not every AML cell had T-IC capacity. A
CD34 positive/CD38 negative cell fraction representing 0.1 to 1 percent of the
tumor cells possessed all the leukemia initiating activity in the NOD/SCID
transplantation model. By contrast, the major fraction of the CD34
positive/CD38 positive cells and the majority of CD34 negative cells, which
comprise most of the cells in the tumor, could not initiate leukemia. A
multiple myeloma stem cell has also been characterized. Multiple myeloma cell
lines and primary patient derived cells express the cell surface marker
syndecan-1 (CD138). A population of cells representing less than 5 percent of
the cells in the bulk population of multiple myeloma cells was found to be
CD138 negative, and possessed in vitro clonogenic potential. These cells also
engrafted successfully into Non-obese Diabetic/Severe Combined Immunodeficient
(NOD/SCID mice), whereas CD138 positive cells did not engraft.
Recently, a mammary carcinoma stem cell has been isolated from primary mammary
carcinomas using four cell surface markers (CD44; CD24; a mammary tumor marker,
and epithelial specific antigen). The tumor initiating capacity of the cells
was again verified in an in vivo NOD/SCID engraftment assay. The mammary tumor
stem cells represented only 2 percent of the unfractionated bulk tumor cells.
Finally, a putative brain tumor stem cell has also been isolated. These cells
appear to be between 0.3 to 25 percent of the cells in the brain tumors
examined. They are positive for the neural stem cell marker CD133 and have a
marked capacity for self renewal and differentiation. Transplantation of these
putative neural tumor stem cells into the forebrains of NOD/SCID mice yields
tumors phenotypically resembling the tumors from which the stem cells were
isolated.
Isolation of tumor stem cells from a larger spectrum of solid tumors and
characterization of markers for such cells will be important in understanding
how general the role of tumor stem cells are in the pathogenesis of cancer.
In addition to isolating and characterizing tumor stem cells themselves, it is
also important to identify the genes and proteins that facilitate the self
renewal phenotype that characterize all stem cells. The proteins involved in
self renewal in embryonic and adult stem cells appear to be subverted in
tumorigenesis to allow the tumor-initiating cells to maintain self renewal
capacity. Two families of proteins related to self renewal, the polycomb gene
Bmi-1 and the Wnt signaling pathway proteins, have been related to the
maintenance of the tumor stem cell phenotype.
The polycomb genes have an essential role in embryogenesis, regulation of the
cell cycle, and lymphopoieisis. These genes are transcriptional repressors that
are essential for the silencing of other families of genes. Deletion of
polycomb gene Bmi-1 in mice results in a progressive loss of all hematopoietic
lineages. This loss results from the inability of the Bmi-1(-/-) stem cells to
self renew. Introducing genes known to produce AML into Bmi-1(-/-)
hematopoeitic stem cells (fetal liver cells), induced AML with normal kinetics;
however, the Bmi-1(-/-) leukemic stem cells from primary recipients were unable
to produce AML in secondary recipients. These results demonstrate that Bmi-1 is
also required for self renewal of leukemic stem cells in the murine AML model.
Another group of genes involved in self renewal are those involved in the Wnt
signal transduction cascade. The Wnt protein binds to a receptor called
Frizzled and activates cell fate decisions during tissue development.
Inhibitors of Wnt signaling produce inhibition of hematopoietic stem cell
growth in vitro and reduce hematopoietic reconstitution in vivo. Activation of
Wnt signaling in hematopoeitic stem cells leads to increased expression of Hox
B4 and Notch-1 genes previously implicated in self renewal of hematopoietic
stem cells. The Wnt signaling pathway is involved in both hematopoietic
malignancy and colon carcinoma. Although the Wnt ligands themselves are only
rarely involved in tumorigenesis, mutations mimicking Wnt receptor (Frizzled)
activation induce a set of genes associated with repression of differentiation
and potentiation of self renewal. In general, these mutations involve Wnt
signal transduction proteins including the activation of beta- catenin and
inactivation of the (APC) adenomatosis polyposis coli protein. In myeloid
leukemia, non-phosphorylated beta_catenin accumulates in granulocyte-macrophage
progenitors as they progress toward leukemia. These normally more committed
progenitors can thus acquire self-renewal properties. A similar accumulation of
unphosphorylated beta- catenin has also been observed in multiple myeloma
cells. In colon cancer, the APC gene is mutated early in the development of
about 90 percent of the colon carcinomas. Similarity in gene expression
patterns between populations of colon cancer cells and colon epithelial stem
cells has also been observed by DNA microarray analysis. It is possible that
mutations in the Wnt signaling pathway maintain the program of stem cell genes
in the transcriptionally active state.
Additional research on the important genes and proteins that function to
maintain the stem cell phenotype could contribute to increasing the number of
specific targets for which cancer therapeutic agents can be designed.
Recent studies of Helicobacter infection in mice have suggested that bone
marrow hematopoietic stem cells can contribute to repopulating the gastric
mucosal epithelium. These cells can progress, with time, to metaplasia,
dysplasia, and cancer. The possibility of stable fusion between the bone marrow
derived cells and the gastric mucosa was eliminated, suggesting the possibility
of transdifferentiation of hematopoietic stem cells. Research aimed at
establishing whether or not stem cells have the capacity to transdifferentiate
is also encouraged.
Objectives and Scope
This funding opportunity is intended to promote research on all aspects of tumor stem cell biology, and on the genes and proteins responsible for the tumor stem cell phenotype. Research studies on the characterization of tumor stem cells from the broad spectrum of solid and liquid tumors not already examined, on markers potentially shared by tumor stem cells and normal stem cells, and on the biochemical and molecular regulation of normal and tumor stem cell function are encouraged. Such research can and should include research on in vivo assays for the functional identification of such cells. Studies of the genes regulating self renewal, and studies of regulation of stem cell division by the stem cell niche and/or microenvironment are also encouraged. Investigators working on the cell and molecular biology of embryonic stem cells, adult stem cells, and tumor stem cells are encouraged to apply for support under this funding opportunity. The following questions illustrate areas of high interest, but other relevant innovative projects are also encouraged.
Section III. Eligibility Information
1. Eligible Applicants
1.A. Eligible Institutions
You may submit (an) application(s) if your
organization has any of the following characteristics:
1.B.
Eligible Individuals
Any individual with the skills, knowledge, and
resources necessary to carry out the proposed research as the Project
Director/Principal Investigator (PD/PI) is invited to work with his/her
organization to develop an application for support. Individuals from
underrepresented racial and ethnic groups as well as individuals with
disabilities are always encouraged to apply for NIH support.
2. Cost Sharing or
Matching
Not applicable. This program does not require
cost sharing as defined in the current NIH
Grants Policy Statement.
3. Other-Special
Eligibility Criteria
Applicants may submit more
than one application, provided 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, link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.
A one-time registration is required for institutions/organizations at both:
PDs/PIs should work with their institutions/organizations to make sure
they are registered in the eRA Commons.
Several additional separate actions are required before an applicant
institution/organization can submit an electronic application, as follows:
1) Organizational/Institutional Registration in Grants.gov/Get Started.
2) Organizational/Institutional Registration in the eRA Commons
3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.
Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.
Several of the steps of the registration
process could take 4 weeks or more. Therefore, applicants should immediately
check with their business official to determine whether their institution is
already registered in both Grants.gov and
the Commons. The NIH will
accept electronic applications only from organizations that have completed all
necessary registrations.
1. Request Application
Information
Applicants must download the SF424 (R&R)
application forms and SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.
Note: Only the forms package directly attached to a specific FOA can be used.
You will not be able to use any other SF424 (R&R) forms (e.g., sample
forms, forms from another FOA), although some of the "Attachment"
files may be useable for more than one FOA.
For further assistance, contact GrantsInfo; Telephone:
301-710-0267, E-mail: [email protected].
Telecommunications for the hearing impaired: TTY
301-451-5936.
2.
Content and Form of Application Submission
Prepare all applications using the SF424 (R&R) application forms and in
accordance with the SF424 (R&R) Application Guide
(MS
Word or PDF).
The SF424 (R&R) Application Guide is critical to submitting a
complete and accurate application to NIH. There are fields within the SF424
(R&R) application components that, although not marked as mandatory, are
required by NIH (e.g., the Credential log-in field of the Research &
Related Senior/Key Person Profile component must contain the PD/PI’s assigned
eRA Commons User ID). Agency-specific instructions for such fields are
clearly identified in the Application Guide. For additional information, see
Tips and Tools for Navigating Electronic Submission on the front page of Electronic
Submission of Grant Applications.
The SF424 (R &R) application is comprised of data arranged in separate
components. Some components are required, others are optional. The forms
package associated with this FOA in Grants.gov/APPLY will include all applicable components, required and
optional. A completed application in response to this FOA will include the
following components:
Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site
Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
Research & Related Budget
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398
Modular Budget
Optional Components:
PHS398 Cover Letter File
Note:
While both budget components are included in the SF424 (R&R) forms package,
the NIH R21 uses ONLY the PHS 398 Modular Budget. (Do not use the detailed
Research & Related Budget.)
Foreign
Organizations:
Several special provisions apply to applications
submitted by foreign organizations:
Proposed research should provide a
unique research opportunity not available in the United States.
3. Submission Dates
and Times
See Section IV.3.A for details.
3.A. Submission, Review,
and Anticipated Start Dates
Opening Date: May 2, 2006
Letter of Intent Receipt Date(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.
Upon receipt, applications will be transferred
from Grants.gov to the NIH Electronic Research Administration process for
validation. Both the PD/PI and the SO for the organization must verify the
submission via Commons within 2 business days of notification of the NIH validation.
Upon receipt, applications will be evaluated for
completeness by the Center for Scientific Review, NIH. Incomplete applications
will not be reviewed.
There will be an acknowledgement of receipt of
applications from Grants.gov and the Commons. Information related to the
assignment of an application to a Scientific Review Group is also in the Commons.
The NIH will not accept any
application in response to this FOA that is essentially the same as one
currently pending initial merit review unless the applicant withdraws the
pending application. The NIH will not accept any application that is
essentially the same as one already reviewed. This does not preclude the submission
of an application already reviewed with substantial changes, but such
application must include an Introduction addressing the previous critique.
Note such an application is considered a "resubmission" for the SF424
(R&R).
4. Intergovernmental
Review
This initiative is not subject to intergovernmental
review.
5. Funding Restrictions
All NIH awards are subject to the terms and
conditions, cost principles, and other considerations described in the NIH Grants
Policy Statement.
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 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 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 are to be followed, with the following requirements for R21
applications:
Note: While each section of the Research Plan needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.
Plan
for Sharing Research Data
Not applicable.
Sharing Research
Resources
NIH policy requires that grant awardee
recipients make unique research resources readily available for research
purposes to qualified individuals within the scientific community after
publication (see the NIH
Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131).
Investigators responding to this funding opportunity should include a plan for
sharing research resources addressing how unique research resources will be
shared or explain why sharing is not possible.
The adequacy of the resources sharing plan and any
related data sharing plans will be considered by Program staff of the funding
organization when making recommendations about funding applications. The
effectiveness of the resource sharing will be evaluated as part of the
administrative review of each Non-Competing Grant
Progress Report (PHS 2590). See Section VI.3.,
Reporting.
Section V. Application Review Information
Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications. The following will be considered in making funding decisions:
The
NIH R21 exploratory/developmental grant is a mechanism for supporting novel
scientific ideas or new model systems, tools, or technologies that have the
potential to significantly advance our knowledge or the status of
health-related research. Because the Research Plan is limited to 15 pages, an
exploratory/developmental grant application need not have extensive background
material or preliminary information as one might normally expect in an R01
application. Accordingly, reviewers will focus their evaluation on the
conceptual framework, the level of innovation, and the potential to
significantly advance our knowledge or understanding. Reviewers will place less
emphasis on methodological details and certain indicators traditionally used in
evaluating the scientific merit of R01 applications, including supportive
preliminary data. Appropriate justification for the proposed work can be
provided through literature citations, data from other sources, or, when
available, from investigator-generated data. Preliminary data are not required
for R21 applications; however, they may be included if available.
The goals of NIH supported research are to advance our
understanding of biological systems, to improve the control of disease, and to
enhance health. In their written critiques, reviewers will be asked to comment
on each of the following criteria in order to judge the likelihood that the
proposed research will have a substantial impact on the pursuit of these goals.
Each of these criteria will be addressed and considered in assigning the
overall score, weighting them as appropriate for each application.
Note that an application does not need to be strong in all categories to be
judged likely to have major scientific impact and thus deserve a high priority
score. For example, an investigator may propose to carry out important work
that by its nature is not innovative but is essential to move a field forward.
Significance: Does this study address an important problem? If the aims
of the application are achieved, how will scientific knowledge or clinical
practice be advanced? What will be the effect of these studies on the concepts,
methods, technologies, treatments, services, or preventative interventions that
drive this field?
Approach: Are the conceptual or clinical framework, design, methods,
and analyses adequately developed, well integrated, well reasoned, and
appropriate to the aims of the project? Does the applicant acknowledge
potential problem areas and consider alternative tactics?
Innovation: Is the project original and innovative? For example: Does
the project challenge existing paradigms or clinical practice; address an
innovative hypothesis or critical barrier to progress in the field? Does the
project develop or employ novel concepts, approaches, methodologies, tools, or
technologies for this area?
Investigators: Are the investigators appropriately trained and well suited
to carry out this work? Is the work proposed appropriate to the experience
level of the PD/PI and other researchers? Does the investigative team bring
complementary and integrated expertise to the project (if applicable)?
Environment: Does the scientific environment in which the work will be
done contribute to the probability of success? Do the proposed studies benefit
from unique features of the scientific environment, or subject populations, or
employ useful collaborative arrangements? Is there evidence of institutional
support?
2.A. Additional Review
Criteria
In addition to the above criteria, the following
items will continue to be considered in the determination of scientific merit
and the priority score:
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 SF 424 (R&R) will be assessed.
2.B.
Additional Review Considerations
Budget and
Period of Support:
The reasonableness of the proposed budget and the appropriateness of the
requested period of support in relation to the proposed research may be
assessed by the reviewers. Is the effort listed for the PD/PI appropriate for
the work proposed? Is each budget category realistic and justified in terms of
the aims and methods?
2.C. Sharing
Research Data
Not applicable.
2.D. Sharing
Research Resources
NIH policy requires that grant awardee recipients make
unique research resources readily available for research purposes to qualified
individuals within the scientific community after publication (see the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131).
Investigators responding to this funding opportunity should include a plan for
sharing research resources addressing how unique research resources will be
shared or explain why sharing is not possible.
Program staff will be responsible for the
administrative review of the plan for sharing research resources.
The adequacy of the resources sharing plan and any related data sharing plans
will be considered by Program staff of the funding organization when making
recommendations about funding applications. The effectiveness of the resource
sharing will be evaluated as part of the administrative review of each Non-Competing Grant
Progress Report (PHS 2590), See Section VI.3.,
Reporting.
3.
Anticipated Announcement and Award Dates
Not
applicable.
Section VI. Award Administration Information
1. Award Notices
After the peer review of the application is completed, the PD/PI will be
able to access his or her Summary Statement (written critique) via the NIH eRA Commons.
If the application is under consideration for
funding, NIH will request "just-in-time" information from the
applicant. For details, applicants may refer to the NIH
Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards,
Subpart A: General.
A formal notification in the form of a Notice of Award
(NoA) will be provided to the applicant organization. The NoA signed by the
grants management officer is the authorizing document. Once all administrative
and programmatic issues have been resolved, the NoA will be generated via
e-mail notification from the awarding component to the grantee business
official.
Selection of an application for award is not an
authorization to begin performance. Any costs incurred before receipt of the
NoA are at the recipient's risk. These costs may be reimbursed only to the
extent considered allowable pre-award costs. See Section
IV.5., Funding Restrictions.
2. Administrative and National Policy Requirements
All NIH grant and cooperative agreement awards include
the NIH Grants Policy Statement as part of the NoA. For these terms of
award, see the NIH
Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards,
Subpart A: General and Part
II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions
for Specific Types of Grants, Grantees, and Activities.
2.A. Cooperative
Agreement Terms and Conditions of Award
Not applicable.
3. Reporting
When multiple years are involved, awardees will be
required to submit the Non-Competing Grant
Progress Report (PHS 2590) annually and financial statements as required in
the NIH
Grants Policy Statement.
Section
VII. Agency Contacts
We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues.
1. Scientific/Research Contacts:
R. Allan Mufson, Ph.D.
Chief, Cancer Immunology Hematology Branch
Division of Cancer Biology
National Cancer Institute
6130 Executive Boulevard, EPN Room 5062, MSC 7388
Bethesda, MD 20892-7388 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery)
Telephone: 301-496-7815
FAX: 301-480-2844
E-mail: [email protected]
Jill Carrington, Ph.D.
Chief, Systems Branch
Director, Musculoskeletal Biology
Biology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue, Suite 2C231, MSC 9205
Bethesda, MD 20892-9205
Telephone: 301-496-6402
FAX: 301-402-0010
E-mail: [email protected]
2. Peer Review Contacts:
Not applicable.
3. Financial or Grants Management Contacts:
Annette Hanapole
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)
Telephone: (301) 496-8627
FAX: (301) 496-8601
E-mail: [email protected]
Linda Whipp
Grants and Contracts Management Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2N212, MSC 9205
Bethesda, MD 20892-9205
Telephone: 301-496-1472
FAX: 301- 402-3672
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. 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.
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
|
| ||||||
|
|
|
Department of Health and Human Services (HHS) |
|
|||
|
NIH... Turning Discovery Into Health® |
||||||