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)
Title: Tumor Stem Cells in
Cancer Biology, Prevention, and Therapy (P01)
Announcement Type
New
Request For Applications (RFA) Number: RFA-CA-08-020
Catalog of Federal Domestic Assistance Number(s)
93.393, 93.394, 93.395, 93.396, 93.399
Key Dates
Release Date: March 26, 2008
Letters of Intent Receipt Date: June 10, 2008
Application Receipt Date: July 10, 2008
Peer Review Date: October/November
2008
Council Review Date: January 2009
Earliest Anticipated Start Date: April 2009
Additional
Information To Be Available Date (URL Activation Date): Not Applicable
Expiration Date: July 11, 2008
Due Dates
for E.O. 12372
Not Applicable.
Additional Overview Content
Executive Summary
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(s) 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. Address to 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. Sending an Application to
the NIH
C. Application Processing
D. Application Assignment
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 Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)
Section VIII. Other Information
- Required Federal Citations
Part II
- Full Text of Announcement
Section I. Funding Opportunity Description
1. Research Objectives
Purpose
This Funding Opportunity Announcement (FOA) for P01 applications is intended to stimulate innovative, multidisciplinary, interactive, and synergistic program projects that integrate basic and translational aspects of tumor stem cell biology. An improved understanding of the biology of tumor stem cells is expected to facilitate the development of effective preventive and therapeutic strategies. The identification of new biomarkers for improved cancer detection, diagnosis, and prognosis is also possible.
The goal is the translation of basic research findings into clinical practice in the context of both hematological and solid tumor malignancies. Applications submitted in response to this FOA must propose interdisciplinary Program Projects that comprehensively address novel aspects of the biology of tumor stem cells (tumor initiating cells) combined with the meaningful translation of basic research findings into clinical-relevant context. For these goals, it is essential that each proposed Program Project is based on appropriate substantive collaborative arrangements between basic and translational researchers,
In addition to this RFA for Program Project (P01) Grants, another RFA of essentially identical scientific scope (RFA-CA-08-019), uses the NIH Research Project (R01) grant mechanism. To inspire new research and facilitate dissemination of the results within the entire stem cell research program, the NCI will encourage (and facilitate) interactions among both the R01 and P01 awardees associated with both Stem Cell initiatives via periodic joint meetings.
Background
Despite progress in the early detection and treatment of malignant disease, existing cancer therapies are limited in their ability to completely eradicate tumors or to prevent recurrence and progression to metastasis. Tumors and distant metastases frequently recur, even after completion of therapy. In addition, existing therapies are relatively non-specific and highly toxic, often killing normally proliferating cells as well as tumor cells. New cellular and mechanistic insights are required to understand why current preventive and therapeutic interventions have limited efficacy, and why tumor metastases recur. The concept of a self-renewing population within the tumor, the tumor stem cells, offers the potential to provide these insights. Ongoing characterization of tumor stem cells promises to be highly translational, providing new targets for early detection and for preventive and therapeutic interventions.
Although the concept of a tumor stem cell has been postulated for many years, only in the last decade has the existence of rare populations of self-renewing cells been demonstrated within hematopoietic and some epithelial cancers. These cells, referred to by various terms such as tumor initiating, tumor stem, or cancer initiating cells, may be responsible for driving tumor development, progression, and metastasis. In many cases, these cells comprise only a small sub-population within the tumor, but have the potential to propagate the tumor. Thus, human tumor stem cells can recapitulate the complete phenotype of the original human tumor following serial xenografts into immune-compromised mice. In contrast, the bulk of the cells in the tumor lack this capacity.
Tumor stem cells have been characterized and isolated based on their expression of various cell surface molecules. These phenotypic markers vary among tumor stem cells of differing origin. Tumor stem cells were first characterized in acute myeloid leukemia (AML) and found to have the characteristic phenotype of CD34+, CD38-, CD123+. Subsequently, tumor stem cells have been identified in mammary carcinoma (CD44+, CD24lo), several brain tumors (CD133+, nestin+), and in colon cancer and melanoma (CD133+). It is still not clear whether tumor stem cells are present in all tumors. In a transgenic mouse model, most of the cells of a lymphoma (driven by the oncogene E -myc) had the ability to recapitulate the tumor in transplantation models. However, the possibility could not be excluded that, in this E -myc transgenic mouse model, the lymphoma consists of a homogenous population of less differentiated cells exhibiting a greater proliferative capacity greater than the human models previously examined.
Various questions remain unanswered about the prevalence of tumor stem cells in specific tumor types. Nonetheless, the already collected data in various models begin to implicate stem cells in the resistance of tumors to complete eradication by current therapies. Tumor stem cell populations may have inherent resistance to chemotherapeutic agents that efficiently target the bulk of tumor cells. In support of this interpretation, normal stem cells demonstrate a resistance to current chemotherapeutic agents through the expression of several ATP binding cassette (ABC) transporters. Among these transporters is breast cancer resistance protein (BCRP), which is expressed in normal hematopoietic CD34+ stem cells. The presence of BCRP-1 mRNA is associated with a subpopulation of tumor cells that includes tumor stem cells. These populations are capable of ex vivo expansion and show evidence of asymmetric cell division. Importantly, these cells have the enhanced capacity to expel cytotoxic drugs. Thus, several aspects of tumor stem cell biology could be extremely important for understanding the basis for the limitations in current cancer therapies.
The central feature of tumor stem cells is their relatively unlimited self-renewal capacity and their asymmetric cell division. These properties can contribute to tumor expansion, as well as account for tumor metastasis. However, the molecular and biochemical mechanisms providing self-renewal capacity to tumor cells are incompletely understood. Since self-renewal is also a defining characteristic of normal stem cells, studies with normal cells can provide some insights into tumor stem cell biology. A number of genes have been implicated in regulating asymmetric division in normal stem cells. Among those genes are BMI-1, Wnt, -catenin, Notch, Hedgehog, and members of the HOX gene family. Interestingly, alterations in these genes also have been observed in epithelial and hematological malignancies. BMI-1 is a member of the polycomb family of transcriptional repressors that are essential for the silencing of other families of genes. A deletion of the BMI-1 gene in mice results in the progressive loss of all hematopoietic lineages due to the inability of BM-1-deficient stem cells to self renew. Introducing genes known to cause AML into BMI-1-deficient murine hematopoietic cells (i.e., fetal liver cells) induced AML with normal growth kinetics. However, the BMI-1-deficient leukemic stem cells were unable to produce AML in secondary transplant recipients. Thus, BMI-1 is required for the self-renewal capacity of these AML stem cells.
Another example of the similarities between normal and tumor stem cell regulation is the shared importance of the Wnt/ -catenin signaling pathway in both types of stem cells. Activation of the Wnt receptor causes accumulation of -catenin in the cytoplasm, which eventually translocates into the nucleus. The nuclear translocation of -catenin drives the expression of genes associated with self-renewal. In the development of AML, -catenin accumulates in the nucleus of granulocyte macrophage progenitors, as they progress toward leukemia. Therefore, these normally more committed progenitors can acquire self-renewal properties. A similar accumulation of -catenin also has been observed in multiple myeloma, suggesting that aberrations in this pathway may be more broadly associated with the acquisition of self-renewal properties. Mutations in the Wnt signaling pathway may maintain stem cell related genes in the on position. Understanding the role of the Wnt signaling pathway in promoting self-renewal already promises to result in translational applications. A small molecule inhibitor of the Wnt signaling pathway, PKF 115-584, decreases Wnt target gene expression, induces in vitro cytotoxicity in myeloma cell lines, and retards growth of multiple myeloma xenograft models in vivo.
Specific Requirements, Objectives and Scope
Research projects proposed in response to this FOA may address diverse aspects of tumor stem cell biology, but they must involve interdisciplinary, integrative, and collaborative research with a strong emphasis on the translation of the findings into clinically-relevant applications. Translational research is defined by the NCI as research activities which transform scientific discoveries arising from laboratory, clinical, or population studies into clinical applications to reduce cancer incidence, morbidity, and mortality (for details visit the web site of the NCI Translational Research Working Group, TRWG). Researchers should focus on the unique characteristics of human tumor stem cells and their niche or microenvironment to develop, for example, new markers for early detection, diagnosis, and prognosis as well as identify, characterize, and validate new targets for prevention and/or therapy.
To ensure such integrated, translation-oriented approach, each application must consist of at least three individual research projects, all of which must be pertinent to a single unifying research theme. At least one of these projects must address basic aspects of tumor cell biology and at least one project must center on translation of such basic research findings into clinically-relevant context. The required third project may focus on either basic or translational research or combine both aspects, as appropriate for the overall goal of the Program Project. It is expected that the proposed Program Projects will involve substantive collaborative arrangements between basic and translational researchers. Therefore, applicants are encouraged to consider the Multiple Principal Investigators option.
Examples of pertinent research directions that may be addressed in response to this FOA (provided appropriate translational component is also proposed) include, but are not limited to, the following questions:
Translational studies may exploit in the clinical context basic research advances in any of the above-listed areas or in other areas related to cancer stem cell research.
Although the listed research areas are of definite importance, applications in all areas related to tumor stem cell research with translational impact are encouraged. To be responsive to this FOA, the overarching goal of the entire Program Project must have direct translational relevance to clinical oncology, including prevention, diagnosis, and therapy of malignant disease.
Shared Resource Core(s) (optional)
In addition to individual research projects, the applicants may propose one or more Shared Resource Cores, if needed. Both administrative and research support cores are allowed. Each Shared Resource Core must be designed to provide support and enhance the productivity, cost-effectiveness, and/or research outcome of at least two research projects.
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 Program Project Grant (P01)
mechanism. The P01 supports broadly based multidisciplinary
research programs that have a well defined central research focus or
objective. An important feature is that the interrelationships among the
individual projects will result in a greater contribution to the overall
program goals than if each project were pursued independently. The P01
application requires that each application must propose at least three
individual (albeit connected) research projects pertinent to a single unifying
research theme. At least one of these projects must address basic aspects of
tumor cell biology and at least one project must center on translation of such
basic research findings into a clinically-relevant context. The other projects
may focus on either basic or translational research or combine both aspects. As
an option, and if needed, the application may
request support for certain shared resource cores.
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. It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html).
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 and the receipt of a sufficient number of meritorious
applications.
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:
Whereas Foreign institutions are not eligible to apply, they can be involved in Program Projects proposed by eligible Domestic institutions under subcontractual arrangements, if appropriate.
1.B. Eligible Individuals
Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
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, 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 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 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 multiple PDs/PIs, 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
Resubmission
applications are not permitted in response to this FOA.
Renewal applications are not permitted in response to this FOA.
Applicants may submit more than one application, provided each application is scientifically distinct.
To encourage substantive collaborative arrangements between basic and translational researchers, a minimal commitment of lead basic and translational investigators [PI(s) and Project Leaders] is expected to be not less than 15 percent effort each for the entire P01. The individual percentage effort can be distributed amongst projects and cores. A strong justification must be provided if lesser effort level is proposed.
Section IV. Application and Submission Information
1. Address
to Request Application Information
The PHS 398 application
instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of
the PHS 398. For further assistance, contact GrantsInfo -- Telephone: (301)
710-0267; Email: [email protected].
Telecommunications for
the hearing impaired: TTY 301-451-5936.
2. Content and Form of Application Submission
Applications must be
prepared using the current PHS 398 research grant application instructions and
forms PHS 398 grant
application instructions as modified in the NCI guidelines for the preparation of Program Project P01 applications (NCI P01 Guidelines). For
details not covered in this FOA, all applicants should follow these NCI guidelines.
Applications must have a D&B Data Universal
Numbering System (DUNS) number as the universal identifier when applying for
Federal grants or cooperative agreements. The D&B number can be obtained by
calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number
should be entered on line 11 of the face page of the PHS 398 form.
The title and
number of this funding opportunity must be typed on lines 1 and 2 of the face
page of the application form and the YES box must be checked.
ORGANIZATION OF THE APPLICATION
All the applications must conform to the instructions and obey page limitations as stated in Section V (Items A-I) of the NCI P01 Guidelines SPECIAL INSTRUCTIONS for PREPARATION of PROGRAM PROJECT APPLICATIONS . This section of the NCI P01 Guidelines defines and provides detailed instructions on the preparation of the following main application components:
Note: Each P01 applicant must propose at least three individual (albeit connected) research projects pertinent to a single unifying research theme. At least one of these projects must address basic aspects of tumor cell biology and at least one project must center on translation of such basic research findings into a clinically-relevant context. The other projects may focus on either basic or translational research or combine both aspects.
Applications with Multiple PDs/PIs
When multiple PD/PIs are proposed, use the Face Page-Continued page to provide Items 3a 3h for all PD/PIs. NIH requires one PD/PI be designated as the contact PD/PI for all communications between the PD/PIs and the agency. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PD/PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PD/PI may be changed during the project period. The contact PD/PI should be listed in block 3 of Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in the header of each application page, use the name of the Contact PD/PI, et. al. The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.
All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles such as SO or IAR will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.
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 must be included (within the stated above page limits of the Program Narrative: Overall Program Project). 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.
Note 1: During the funding period, all awardees will be required to participate in periodic (annual) joint meetings to be organized by the NCI to share recent results and progress. Appropriate travel funds must be budgeted for the participation in these meetings of the PIs and Project Leaders.
Note 2: If applicants propose to have and External Advisory Board, they must be prepared to identify non-affiliated experts as potential appointees. The applicants should describe the desired scientific profiles of such external advisors. However, in order not to adversely affect the process of peer review of the applications, names of such individuals must not be provided in the application. Moreover, the applicants must not contact these individuals unless their application is selected for funding after the completion of the peer review process.
3.
Submission Dates and Times
Applications must be
received on or before the receipt date described below (Section
IV.3.A). Submission times N/A.
3.A. Receipt, Review, and Anticipated Start Dates
Letters
of Intent Receipt Date: June 10, 2008
Application Receipt Date: July 10, 2008
Peer Review Date: October/November 2008
Council Review Date: January 2009
Earliest
Anticipated Start Date: April 2009
3.A.1.
Letter of Intent
Prospective
applicants are asked to submit a letter of intent that includes the following
information:
Although a letter of
intent is not required, is not binding, and does not enter into the review of a
subsequent application, the information that it contains allows IC staff to
estimate the potential review workload and plan the review.
The letter of intent is to be sent by the date listed
in Section IV.3.A.
The letter of intent should be sent to:
R. Allan Mufson, Ph.D.
Chief, Cancer immunology and 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 non-USPS delivery)
Telephone:
301-496-7815
Fax: 301-480-2844
Email: [email protected]
3.B. Sending an
Application to the NIH
Applications must be
prepared using the forms found in the PHS 398 instructions for preparing a
research grant application. Submit a signed, typewritten original of the
application, including the checklist, and three signed photocopies in one package to:
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (for U.S. Postal Service
express or regular mail)
Bethesda, MD 20817 (for non-USPS delivery)
Personal
deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).
At the time of submission, two additional paper copies of the application
and all 5 copies of the appendix material on CD only (in the same package) must
be sent to :
Referral Officer
National Cancer Institute
Division of Extramural Activities
6116 Executive Boulevard,
Room 8041, MSC 8329
Bethesda,
MD 20892-8329 (for U.S. Postal Service Express or
regular mail)
Rockville,
MD 20852 (for non-USPS delivery)
Telephone: (301) 496-3428
Fax: (301) 402-0275
Email:[email protected]
3.C. Application
Processing
Applications must be submitted on or
before the application receipt/submission dates described above (Section IV.3.A.). If an application is received after
that date, the application may be delayed in the review process or not
reviewed. Upon receipt, applications will be evaluated for completeness
by the CSR and for responsiveness by the reviewing Institute Incomplete and/or
non-responsive applications will not be reviewed.
The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application.
However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.
Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at https://commons.era.nih.gov/commons/.
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. The Grants Policy Statement can
be found at 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: 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 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 at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.)
6. Other Submission Requirements and Information
During the funding period, all awardees of the program on Tumor Stem Cells in Cancer Biology, Prevention, and Therapy (both R01 and P01) will be required to participate in periodic (annual) joint meetings to be organized by the NCI to share recent results and progress. Applications should include meeting attendance costs in the budget.
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.
Appendix Materials
All paper PHS 398 applications submitted for May 25, 2008, and subsequent due dates must provide appendix material on CD only, and include five identical CDs in the same package with the application.
Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe 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 of, and advance 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 Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.
(a) Data Sharing Plan: Investigators seeking $500,000 or more in direct costs in any year 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 (such as 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, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.
Section V. Application Review Information
1. Criteria
Only the review criteria
described below will be considered in the review process.
2. Review and Selection Process
Applications that are complete and
responsive to the FOA will be evaluated for scientific and technical merit by an
appropriate peer review group convened by the NCI and in accordance with NIH peer review
procedures (http://grants1.nih.gov/grants/peer/),
using the review criteria stated below.
As part of the scientific peer review, all applications will:
The following will be considered in making funding decisions:
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 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.
The following general (NIH-wide) criteria will be used in evaluating applications:
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 PD/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 PD/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, methodologies, tools, or technologies for this area?
Investigators: Are the PD(s)/PI(s) and other key personnel appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Do(es) the PD(s)/PI(s) and 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?
CRITERIA SPECIFIC TO THIS FOA
In addition to the standard NIH-wide criteria, the following FOA-specific criteria will be used to evaluate specific aspects/components of the P01 application.
A. Criteria for the Overall Program Evaluation: The overall application will be evaluated as an integrated research effort focused on a central theme. Individual Research Projects, supporting cores, and the administrative structure are collectively considered. For the program project to receive a priority score, it must consist of at least three projects (each found to have significant and substantial merit) for the duration of the project period. The review criteria for the overall P01 Program are as follows:
B. Criteria for Individual Projects: The relationship and contributions of each research component and core to the overall theme of the program project will be discussed and evaluated. Although projects not recommended for inclusion in the program automatically are removed from consideration as part of the overall program project, such projects will reflect on the leadership capabilities of the Principal Investigator and shall be considered in the overall merit. The individual projects will be evaluated based on the following criteria:
C. Criteria for Shared Resource Core(s) (IF APPLICABLE): Each Shared Resource Core must provide essential functions or services for at least two projects. The merit of each core will be assessed based on the following criteria:
Does the Shared Resource Core match well the needs of the overall program? Does it provide essential facilities or services for two or more scored research project components? Is each Shared Resource Core unique and not duplicative of any other existing and available Cores (e.g., if P01 originates from an institution supported by an NCI Cancer center Support Grant, P30)? Is adequate justification provided for the usefulness of the Shared Resource Cores to the various research projects? What is the relationship of the Shared Resource Core to the central focus of the overall program? What quality control processes are in place for facilities or services provided by the Shared Resource Cores (including procedures, techniques, and quality control)? What are the criteria for prioritization and usage? Is the Shared Resources Core budget appropriate? What are the qualifications, competence, and commitment of the Shared Resource Core leaders and other key personnel?
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:
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 Research Plan section on Human Subjects in the PHS
398 instructions).
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 Research Plan section on Human Subjects in the
PHS 398 instructions).
Care
and Use of Vertebrate Animals in Research: If vertebrate animals are to
be used in the project, the five points described in the Vertebrate Animals
section of the Research Plan will be assessed.
Biohazards: If materials or procedures
are proposed that are potentially hazardous to research personnel and/or the
environment, determine if the proposed protection is adequate.
2.B. Additional Review
Considerations
Budget: The reasonableness of the
proposed budget and the requested period of support in relation to the proposed
research. The priority score should not be affected by the evaluation of the
budget.
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 RFA. NCI Program staff members 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 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 (designated in
Item 12 on the Application Face Page). If a grantee is not email enabled, a
hard copy of the NoA will be mailed to the 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 also 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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm)
and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and
Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).
3. Reporting
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.
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 and grants
management.
1. Scientific/Research Contacts:
R. Allan Mufson, Ph.D.
Chief, Cancer Immunology and 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 non-USPS delivery)
Telephone: 301-496-7815
Fax: 301-480-2844
Email: [email protected]
Jacob Kagan, Ph.D.
Division of Cancer Prevention
National Cancer Institute
6130 Executive Boulevard,
EPN, Room 3147, MSC 7362
Bethesda,
MD 20892-7362 (for U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: 301-435-1594
Fax: 301-402-8990
Levy Kopelovich, Ph.D.
Division of Cancer Prevention
National Cancer Institute
6130 Executive Boulevard,
EPN Room 2114, MSC 7322
Bethesda,
MD 20892-7322 (for U.S. Postal Service regular and express mail)
Rockville,
MD 20852 (for non-USPS delivery)
Telephone: 301-594-0467
Jerry Collins, Ph.D.
Division of Cancer Treatment and Diagnosis
6130 Executive Boulevard,
EPN Room 8018, MSC 7450
Bethesda,
MD 20892-7450 (for U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: 301-496-8720
Fax: 301-402-0831
Email: [email protected]
2. Peer Review Contacts:
Referral Officer
National Cancer Institute
Division of Extramural Activities
6116 Executive Boulevard,
Room 8041, MSC 8329
Bethesda,
MD 20892-8329 (for U.S. Postal Service Express or
regular mail)
Rockville,
MD 20852 (for non-USPS delivery)
Telephone: (301) 496-3428
Fax: (301) 402-0275
Email:[email protected]
3. Financial or Grants Management Contacts:
Crystal Wolfrey
Office of Grants Administration
National Cancer Institute
6120 Executive Boulevard,
Room 243, MSC 7150
Bethesda,
MD 20892-7150 (For U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-8634
Fax: (301) 496-8601
Email: [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 IRB rules, as well as local, State, and
Federal laws and regulations, including the Privacy Rule. Reviewers will
consider the data sharing plan but will not factor the plan into the
determination of the scientific merit or the priority score.
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/.
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 public
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 http://grants.nih.gov/grants/policy/nihgps_2003/index.htm).
All investigators submitting an NIH application or contract proposal, beginning
with the October 1, 2004 receipt date, are expected to include in the
application/proposal a description of a specific plan for sharing and
distributing unique model organism research resources generated using NIH
funding or state why such sharing is restricted or not possible. This will
permit other researchers to benefit from the resources developed with public
funding. The inclusion of a model organism sharing plan is not subject to a
cost threshold in any year and is expected to be included in all applications
where the development of model organisms is anticipated.
Inclusion of
Women And Minorities in Clinical Research:
It is the policy
of the NIH that women and members of minority groups and their sub-populations
must be included in all NIH-supported clinical research projects unless a clear
and compelling justification is provided indicating that inclusion is
inappropriate with respect to the health of the subjects or the purpose of the
research. This policy results from the NIH Revitalization Act of 1993 (Section
492B of Public Law 103-43). All investigators proposing clinical research
should read the "NIH Guidelines for Inclusion of Women and Minorities as
Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical
trials consistent with the new PHS Form 398; 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 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html)
investigators must submit or have submitted for them their final, peer-reviewed
manuscripts that arise from NIH funds and are accepted for publication as of
April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available
no later than 12 months after publication. As of May 27, 2008, investigators
must include the PubMed Central reference number when citing an article in NIH
applications, proposals, and progress reports that fall under the policy, and
was authored or co-authored by the investigator or arose from the
investigator’s NIH award. 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 (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
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) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide
any other information necessary for 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% 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® |
||||||