Part I Overview Information


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.nci.nih.gov)

Title: Tumor Microenvironment Network (TMEN) (U54)
  
Announcement Type
New

Update: The following update relating to this announcement has been issued:

Request For Applications (RFA) Number: RFA-CA-06-014

Catalog of Federal Domestic Assistance Number(s)
93.393, 93.394, 93.395, 93.396, 93.399

Key Dates
Release Date: February 1, 2006
Letters of Intent Receipt Date(s): April 10, 2006
Application Receipt Dates(s): May 10, 2006
Peer Review Date(s): July–August 2006
Council Review Date(s): September 5-7, 2006
Earliest Anticipated Start Date: September 30, 2006
http://grants.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Additional Information To Be Available Date (URL Activation Date): NA
Expiration Date: May 11, 2006

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

Section II. Award Information
   1. Mechanism of Support  
   2. Funds Available

Section III. Eligibility Information
  1. Eligible Applicants
    A. Eligible Institutions
    
B. Eligible Individuals
  2. Cost Sharing or Matching

  3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
  1. Address to Request Application Information
  
2. Content and Form of Application Submission
  
3. Submission Dates and Times
    A. Receipt and Review and Anticipated Start Dates
      1. Letter of Intent
    B. Sending an Application to the NIH
    C. Application Processing
  4. Intergovernmental Review
  5. Funding Restrictions
  6. Other Submission Requirements

Section V. Application Review Information
  1. Criteria
  2. Review and Selection Process
    A. Additional Review Criteria
    B. Additional Review Considerations
    C. Sharing Research Data
    D. Sharing Research Resources
  3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
  1. Award Notices
  2. Administrative and National Policy Requirements
    A. Cooperative Agreement Terms and Conditions of Award
      1. Principal Investigator Rights and Responsibilities
      2. NIH Responsibilities
      3. Collaborative Responsibilities
      4. Arbitration Process
  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

The National Cancer Institute (NCI) invites cooperative agreement applications from groups of investigators interested in becoming components of the NCI Tumor Microenvironment Network (TMEN, also referred to as the “Network”). TMEN will consist of inter-connected, multidisciplinary teams of investigators and collaborative groups that will work together on projects focused on the tumor microenvironment.

The main objective of the TMEN initiative is to delineate mechanisms of tumor-stroma interactions in human cancer. Such an effort is likely to generate a more comprehensive understanding of the composition(s) of the stroma in normal tissues as well as of the role(s) of the stroma in tumor initiation, progression, and metastasis. Through use of the NIH U54 cooperative agreement mechanism, this funding opportunity is intended to support a network of up to six individual Research Programs, each consisting of multi-disciplinary teams of investigators with expertise in specific tumor site(s) and using human cancer samples and/or well-defined vertebrate models.  

Outside of the set-aside funds for the U54 mechanism, up to two NIH intramural Research Programs are anticipated to be funded as additional non-U54 components of TMEN. NIH intramural project applications will be reviewed and scored with the U54 applications.  The NIH intramural projects selected by the NCI to be components of the TMEN will participate in a manner that is analogous to the U54 awardees.

Investigators funded via this funding opportunity will be part of the TMEN. As members of the Network, grantees will also be expected to participate in collaborative efforts developed within TMEN that are directed at: (1) developing critical resources and reagents; (2) developing novel technologies; and (3) outreach activities to ensure dissemination of such resources and technologies to the broader research community. It is intended that such an infrastructure will not only establish repositories of critical reagents, resources, and information, but also promote and facilitate interdisciplinary collaborations and progress in understanding the role of host stroma in tumorigenesis.

Background

Complex intrinsic and extrinsic influences transform a normal epithelial cell into a malignant one.  Significant advances have been made over the last decades in identifying and understanding the molecular and genetic changes associated with this neoplastic transformation.  This progress involves the identification of oncogenes and tumor suppressor genes and the elucidation of associated signaling mechanisms that modulate growth, survival and proliferation.  These discoveries made it possible to design and develop various novel therapeutic agents that target defined molecular changes in the cancer cell.

Research on tumor-host interactions collectively reveals that: (a) tumors are not masses of autonomous cells, but function like organs composed of many interdependent cell types that contribute to tumor development and metastasis; (b) the interactions between the tumors and their microenvironments are bidirectional and dynamic; and (c) the tumor and its stroma co-evolve during tumor initiation and progression.  The microenvironment is known to be composed of stromal cells that include fibroblasts, immune and inflammatory cells, adipocytes, glial cells, smooth muscle cells, and resident and recruited vascular cells.  Additional components are: the extracellular matrix, growth factors/cytokines, and other proteins produced locally and/or systemically.  Microbial flora may also be present in the tumor microenvironment.

The microenvironment can exert both stimulatory and inhibitory influences on proliferation and malignant properties of tumor cells.  For example, the negative influence is demonstrated in mouse embryos containing teratocarcinoma cells. In this model, the malignant potential of the tumor cells is restrained by the stromal environment, resulting in cancer-free adult mice.  Conversely, numerous examples document the involvement of stroma in pro-neoplastic effects.  Stromal changes play roles in inflammation, which stimulates tumor cell proliferation, angiogenesis, invasion and metastasis which are mediated by cytokines and proteases; and the interaction of host immune cells with the tumor vasculature, which facilitates metastasis.  Stromal cells can also influence organ-specific metastasis as evidenced by the role of stromal-derived chemokines and growth factors (e.g., PTHrP, CXCR4, SDF1, TGF-beta, and RANKL) in metastasis to bone originating from breast and prostate cancers and multiple myeloma.  Finally, an interaction of bone marrow stromal cells with multiple myeloma cells has been shown to contribute to the development of drug resistance.

Evidence is steadily emerging that critical stromal elements of the tumor are attractive targets for cancer prevention, because they primarily influence tumor cells in the early stages of tumor progression.  As targets for therapy, cells in stromal elements of the tumor are less likely to be genetically unstable than tumor cells and are therefore probably less susceptible to the emergence of drug resistance.  Manipulating host-tumor interactions has the potential to reverse the malignant phenotype and reestablish normal control mechanisms.  Recent evidence indicates that stromal cells co-evolve at the earliest onset of cancer, as indicated by genetic or epigenetic changes in stroma, and these changes can specifically be targeted for therapy.  For example, in patients with multiple myeloma, targeting bone marrow stroma with a proteasome inhibitor may attenuate bone metastasis.  In addition, the development of anti-angiogenic drugs (and thalidomide) demonstrates the anti-tumor efficacy of targeting host endothelial cells.

Scientific Goals of Individual Research Programs within the Network:

The NCI has promoted and supported research in the general area of tumor microenvironment for many years.  The NCI has also been receptive to direct input from NCI-funded investigators as well as from participants in various workshops and “think tanks,” all of whom have pointed to the challenges and opportunities in studies of tumor-stromal interactions and related topics.  A major theme that has emerged as a consensus among experts in the field is the need for integrated efforts to define the composition of the stromal compartments in normal and malignant tissues, to delineate how the stroma co-evolves with the tumor, and to assess the impact of the stroma in the cancer initiation-progression-metastasis continuum.

Several recent developments point to considerable potential for fundamental discoveries in the research area pertinent to tumor-host interactions.  These favorable developments include: (a) the availability of various experimental animal and organotypic models; (b) advances in high throughput molecular technologies and laser capture micro-dissection technology that enable molecular analysis of complex tumor-stroma interactions; and (c) concurrent developments in in vivo imaging and microscopy, which provide unique opportunities to delineate the roles of stromal cells in tumor progression and metastasis.

The overall goal of the NCI Tumor Microenvironment Network (TMEN) initiative is to address the emerging opportunities by fostering an integrated collaborative effort among various groups of researchers. It is requested that individual Research Programs propose multidisciplinary approaches for the purposes of understanding the interactions between the cells of the stroma and the tumor, and of delineating their function(s) as they relate to cancer development, progression, and metastasis. Under the auspices of the TMEN, the individual Research Programs need to focus both on defining the mechanisms of tumor-stroma interactions and on studying the normal tissue microenvironment.

It is requested that individual Research Programs proposed in applications responding to this initiative are centered on multidisciplinary approaches aimed at understanding the interactions between the cells of the stroma and the tumor, and at delineating their function(s) as they relate to cancer development, progression, and metastasis. Moreover, these Research Programs should be organized around specific tumor site(s).  It is expected that all Research Programs funded as part of the TMEN initiative will address one or more of the following major scientific areas:

a) the roles of tumor-stroma interactions in tumor initiation and progression, with a focus on characterization of constituent stroma and stromal cells;

b) the roles of inflammatory and other immune cells in tumor initiation and progression; and

c) identification of tumor stem cells and/or other relevant stem cells within the stroma and characterization of their interactions with stromal cells.

Applications responsive to this initiative are expected to be focused on human cancer and/or on well-defined vertebrate models of human cancer.

Specific objectives to achieve the broad goal of characterizing the tumor microenvironment and its interactions with the tumor may include, but are not limited to, the following examples.

a) Characterization of the functions of and interactions among the component cells and matrix molecules in normal organ and tumor-associated stroma, including:

 b) Characterization of the role of the inflammatory and immune cells in the initiation, progression and metastasis of the tumor, including:

 c) Identification of tumor stem cells (and other relevant stem cells within the stroma) and characterization of the interactions between stromal cells and tumor stem cells, including:

d) Identification of alterations in the microenvironment which are critical for tumor development, progression, and metastasis, and elucidation of the mechanisms responsible for these changes, including:

 e) Development of novel technologies and model systems for the study of the microenvironment, including:

Network Goals and Structure:  The overall TMEN goal is to achieve a high-level understanding of stromal composition and tumor-stromal interactions in clinically important tumor sites.  In addition to high scientific productivity of individual Research Programs, this goal requires ensuring that results, ideas, and resources are shared freely within the Network, promoting trans-Network collaborative projects.  Therefore, the TMEN strategy attempts to maximize the benefits of the combined expertise and technological capabilities present in all of the Research Programs (to be represented by the extramural U54 awardees and the NIH intramural research teams) as well as the organizational and programmatic assistance provided by NCI program staff.

To implement the Tumor Microenvironment Network, the NCI will select as components up to six U54 applications, and up to two NIH intramural projects, each supporting a multi-disciplinary team.  Each team will be a self-assembled group of investigators who contribute to the TMEN effort a unique blend of complementary research experience.  It is anticipated that an applicant team will incorporate an appropriate mix of expertise that the team believes is needed to achieve their own goals, and which will contribute substantially to achieving the overall TMEN goals.  Areas of expertise may include, but are not limited to: pathology, cancer biology, cell biology, oncology, engineering, physics, bioinformatics, and experimental models of human diseases.  NCI encourages investigators to use state-of-the-art experimental models such as [animal models with fluorescent markers], and existing technologies for visualizing the components of the stroma at the levels of individual cells and molecules. These technologies include, but are not limited to: multiphoton and deconvolution microscopy, selection of live cells from tumors, stromal markers, 3D matrix reconstitution, and organotypic models.  Collaborations with engineers and physicists who can apply the most current imaging technologies to studies of normal and tumor microenvironments in experimental models or in human cancers are encouraged. 

Through the Network, the individual Research Programs and thereby the investigators, will have access to resources, information, technologies, ideas, and expertise that are beyond the scope of any single research team.  While each funded Program will be largely self-sufficient, investigators will be expected to devote a portion of their effort to participating in collaborative activities with other Network members to improve existing technologies in the field, develop novel reagents, and disseminate information to the research community at-large.  Additional support for these activities will be made available by the NCI as appropriate.  Examples of such collaborative activities include, but are not limited to: (a) developing reagents that will allow identification, purification, and quantitation of the component cells and matrix molecules in normal organ and tumor-associated stroma, so that they may be used as biomarkers of stromal composition and alterations; (b) developing reagents that permit identification and isolation of tumor stem cells; (c) developing reagents that will allow for the identification of stromal stem cells; and (d) developing repositories of stromal cell lines from normal and malignant tissues.

The Network will provide an appropriate venue for close interactions among investigators; facilitate frequent exchange of data and comparison of results obtained across a variety of tumors; and disseminate expertise that may be initially concentrated within a single Research Program.

Individual programs funded through this initiative will operate independently, but they will be linked through a central focus on the tumor microenvironment, a common NCI-supported bioinformatics infrastructure, and a Steering Committee.

Steering Committee Structure and Function:  Both the U54-funded extramural investigators and the NIH intramural investigators will be represented in the TMEN Steering Committee along with NIH representatives. Among its main duties, Steering Committee will: (a) optimize the information flow among the funded Programs and the NCI; (b) provide a central conduit for information dissemination to other NCI- and NIH-funded programs and to the cancer research community; (c) encourage the development of new methodologies and experimental models to be shared among the Network members and with the research community at-large; and (d) identify areas of opportunity that can be best exploited with a group effort via the Network.  Steering committee meetings will be convened twice a year. For details on Steering Committee composition and functions see SectionVI.

The NCI will ensure common access to Network-generated resources and reagents for broader cancer research community. Once TMEN is established, the NCI will also encourage the Network members to interact with existing NCI-supported multidisciplinary groups, such as the Early Detection Research Network, the Mouse Models of Human Cancer Network, the Integrated Cancer Biology Program, and others.

NCI strongly encourages interested investigators to discuss their ideas with involved NCI program staff persons prior to submission of an application to ensure that the proposed research priorities will be responsive to the NCI mission and the intent of this funding opportunity.

Each applicant group should provide evidence of on-going relevant research and institutional resources that augment and sustain the research strengths of the team.  Applicant institutions are encouraged to commit additional dedicated resources in support of any group from their institution that is responding to this funding opportunity announcement.  Applicants are encouraged to seek partners or collaborators from the for-profit private sector where their participation is appropriate.  In structuring these partnerships or collaborations, applicants should take into account pre-existing intellectual property rights associated with the use of existing models/reagents and make appropriate licensing arrangements.  Applicants and their technology licensing offices are encouraged to seek assistance as needed from the NCI Technology Transfer Branch (http://www-otd.nci.nih.gov/) in determining whether such arrangements are appropriate and/or adequate.

In assembling their teams, applicants are encouraged to consider the availability of research expertise, technologic innovations, and potential collaborations from NCI-funded networks and consortia.  These include:  MMHCC (Mouse Models for Human Cancer Network, http://emice.nci.nih.gov/), SPORE (Specialized Programs of Research Excellence) programs (http://spores.nci.nih.gov), Early Detection Research Network (http://www3.cancer.gov/prevention/cbrg/edrn), Small Animal Imaging Resource Program (http://www3.cancer.gov/dip/sairp.htm), the Cancer Genetics Network (http://epi.grants.cancer.gov/CGN), the Cancer Family Registries programs (http://epi.grants.cancer.gov/CFR), The Integrative Cancer Biology Program (http://icbo.nci.nih.gov) and others, which are listed on the NCI website (http://cancer.gov/research_programs/extramural).

To facilitate communications among the participants in the TMEN and between the TMEN and the NCI, the NCI will establish and maintain an Internet-based information technology solution for rapid data and document transmission and electronic communications for the TMEN.

See Section VIII, Other Information - Required Federal Citations for policies related to this announcement.

Section II. Award Information


1. Mechanism(s) of Support

As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity will use the NIH U54 award mechanism. The NIH U54 is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award."

 This funding opportunity uses the just-in-time budget concepts. It also uses the non-modular budget format described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). A detailed categorical budget for the "Initial Budget Period" and the "Entire Proposed Period of Support" is to be submitted with the application.

 The anticipated award date is September 30, 2006.  At this time, it is not known if this RFA will be reissued.

 The source of support for NIH intramural components will be from existing intramural resources.  Extramural grant funds will not be expended to support the intramural components that are selected as part of the TMEN, or extramural collaborations that are part of intramural applications.

 2. Funds Available

NCI intends to commit a total of approximately $12 million in FY 2006 extramural funds to support up to six U54 grants and the development of common resources in response to this RFA.  An applicant for a U54 grant may request a project period of up to 5 years and a budget for total costs (direct and indirect) not to exceed $1.3 million/year or $6.5 million for the duration of the award.  Budgets for out-years may not exceed [the usual?] incremental increase of 3%.  Because the nature and scope of the proposed research will vary from application to application, the NCI anticipates that the size of each award may also vary.  In addition, the NCI anticipates incorporating up to two NIH intramural projects as components of the Network.  No funds from the amount set aside for this RFA will be used to support intramural projects.  For further budget information pertaining specifically to NIH intramural applications, see the SUBMITTING AN APPLICATION section below regarding "Additional Instructions for NIH Intramural Project Applicants."

Although the financial plans of NCI provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds for this purpose in fiscal year 2006, and the receipt of a sufficient number of meritorious applications.

 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:

NOTE: Foreign institutions are not eligible to apply.  Investigators from foreign institutions may participate as a component of an application submitted by a PI from an institution within the United States of America.

NOTE: Intramural components of the Institutes of the National Institutes of Health are eligible to submit applications in response to this announcement. Applications from the NIH investigators will be reviewed for their merits together with applications from extramural investigators using the same set of criteria, although only the extramural applicants will compete for the set-aside funds for the U54 awards.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with his/her institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs.

NIH intramural applicants must be designated by their Institutes as Principal investigators; however, they may not receive salary, equipment, supplies, or other remuneration from the RFA set-aside funds for this program.  An NIH intramural Principal Investigator (PI) must obtain the approval of her/his NIH Institute Scientific Director to allocate resources to the project, and must follow both the general application format instructions and the additional guidelines for NIH intramural project applications under "APPLICATION PROCEDURES."  NIH intramural project applications will be reviewed and scored with the U54 applications.  The NIH intramural projects selected by the NCI to be components of the TMEN will participate in a manner that is analogous to the U54 awardees.  An intramural applicant group may include extramural collaborators as subcontracts, but the resources to support any subcontract must be available from intramural sources and not from any set-aside funds for this RFA.

U54 or Non-NIH applicant teams may identify researchers who are intramural staff of the NIH Institutes or Centers as potential collaborators or consultants.  However, for purposes of this RFA, no NIH intramural scientist may agree to collaborate or consult with, commit time and effort to, or be a co-investigator of, any U54 application except for the following situation.  When the TMEN is assembled from the component projects, there may be NIH intramural investigators whose expertise is identified in the funded U54 applications as necessary or desirable to achieve their individual goals, or those of the TMEN.  Those NIH intramural investigators must then obtain the approval of their Institute's Scientific Director to collaborate with the Network, or one of its U54 components, in a specified role, including time and effort.  NIH intramural investigators who are designated in this manner to collaborate in the Network, will not serve on the TMEN Steering Committee.  The participation of any NIH intramural scientist, including those on the Steering Committee who represent the NIH intramural project components of the TMEN, is independent of, and unrelated to, the role of the NCI Program Director as described under "Terms and Conditions of Award."  The NCI anticipates that NIH intramural investigators will contribute substantially to the breadth of scientific and technical expertise of the TMEN.

2. Cost Sharing or Matching

This program does not require cost-sharing as defined in the current NIH Grants Policy Statement at http://grants2.nih.gov/grants/policy/nihgps_2001/part_i_1.htm.

The most current Grants Policy Statement can be found at: http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#matching_or_cost_sharing.

3. Other-Special Eligibility Criteria

An applicant may submit only one application as the PI in response to this funding opportunity announcement.

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) 435-0714, Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. 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 line 2 of the face page of the application form and the YES box must be checked.

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

Letter of Intent Receipt Date: April 10, 2006
Application Receipt Date(s): May 10, 2006
Peer Review Date: July-August 2006
Council Review Date: September 5-7, 2006
Earliest Anticipated Start Date: September 30, 2006

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 NIH staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed at the beginning of this document.

The letter of intent should be sent to:

Suresh Mohla, Ph.D.
Chief, Tumor Biology and Metastasis Research
Division of Cancer Biology
National Cancer Institute
6130 Executive Boulevard, EPN Room 5038, MSC 7364
Bethesda, MD  20892-7364 (for U.S. Postal Service express or regular delivery)
Rockville, MD 20852 (for express/courier delivery)
Telephone:  (301) 435-1878
FAX:  (301) 480-0864
Email: mohlas@mail.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the research grant applications 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 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

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 copies of the application and all copies of the appendix material must be sent to:

Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329 (for U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (for express/courier delivery)
Bethesda MD 20892-8329

Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf.

3.C. Application Processing

Applications must be received on or before the application receipt date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the NCI. Incomplete and 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.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within 8 weeks.

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 http://grants.nih.gov/grants/policy/policy.htm.

Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing continuation 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 NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.

6. Other Submission Requirements

For U54 and NIH intramural applicants to this RFA, only the "Research Plan" section of the PHS 398 grant application is changed.  The remainder of the PHS 398 application form remains the same.

The standard PHS398 "Research Plan" (Sections A-D) is altered as follows:

The applicant should identify clearly in the abstract and more fully in the research plan the specific questions in tumor-host interactions that are to be explored and the new approaches and collaborations that will result from the establishment of the Research Program.  The synergies to be achieved through the establishment of multi-disciplinary teams and novel collaborations should be fully described.  It is anticipated that the application projects will be multi-disciplinary and will draw on a variety of resources.  Thus, a well thought out and carefully described organization is required.  The PI is responsible for ensuring that scientific goals are met, and for developing and managing a decision-making and administrative structure and process that will allow resources to be allocated (and reallocated, if necessary) to meet those goals.  This will be particularly important for multi-institutional programs.  A management plan outlining the organization and administration of the proposed program should be included.

More detailed instructions are described below:

Section 1: Applicant Group.  Applicants should briefly state the major objectives of the project and describe what expertise the group encompasses, as well as specialized or unique facilities, core resources, and services that are available to support these objectives.  In this section, applicants should describe any ongoing grant-supported, institutional, or private sector resources that augment or complement resources for which funding from this RFA is sought.  The roles of all key personnel, collaborators, and consultants who are associated with the application may be briefly described; however, the full extent of activities for each participant should be covered in Section 2. The Principal Investigator of a Research Program must commit a minimum effort of 25%.

Section 2: Scope of Research.  Depending on the composition and structure of the group, this section should be organized as distinct projects, each led by an independent investigator.  Each project description should include Specific Aims, Background and significance, Preliminary Data, and Experimental plan and Design Sections.  Applicants should define the major research questions and opportunities related to tumor-host interactions that their group effort proposes to undertake, and the importance of those questions to human cancer research.  Applicants should describe how they will function as the group conducting inter-dependent projects. The description should also outline the rationale for approaches to be used or planned for development.  Applicants are encouraged to use this section of the application to highlight how the diverse expertise of the group members contributes to the innovation of which the group is capable, the flexibility they possess to redirect research when scientific progress warrants it, and their ability to anticipate new directions, based on their individual experience and ability to contribute to a collective effort.  The roles and expertise of all key personnel, collaborators, and consultants who are associated with the application should be documented; letters from collaborators and consultants should be included in Section I. of the research plan format as specified in the instructions for the PHS form 398 application.

Section 3: Collaborations and Specific Requirements. This section must contain the following items (all items listed count towards the 100 pages combined limit for Sections 1-3).

ADDITIONAL REQUIREMENTS:

Applicants must budget for travel and per diem expenses for the semi-annual Steering Committee meetings.  In all years, applicants must budget for two investigators, the principal investigator and another senior investigator, to attend two Steering Committee meetings.

In addition, applicants must budget for travel and per diem expenses for participation by at least five members of their group (other than the PI and a senior investigator) in either TMEN Steering Committee meetings or other TMEN-organized workshops and symposia (i.e, a minimum of five trips per year). 

Research Programs will be expected to have a Board of Advisors, drawn from experts outside the project.  These advisors will meet annually to review and provide guidance on Network activities.   While a description of the Board’s activities should be included in the application, potential members should not be named, contacted, or selected until an award has been made.  This situation will allow a wider pool of potential reviewers of the application.  Costs for activities of the Board of Advisors should be included in the budget.  

Applicants are advised to send all appendix material in compact discs (CDs).  Hard copies of appendices will not be accepted by the NCI. After the submission of application, no additional supplementary material of any kind will be allowed.

USING THE RFA LABEL:  The RFA label available in the PHS 398 (rev. 5/2001) application form must be affixed to the bottom of the face page of the application.  Type the RFA number, CA-06-014 on the label.  Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review.  In addition, the RFA title, TUMOR MICROENVIRONMENT NETWORK, and number, RFA CA-06-014, must be typed on line 2 of the face page of the application form and the YES box must be marked.  The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf.

SENDING AN APPLICATION TO THE NIH: For U54 applicants only (NIH intramural applicants must use the address in the Section below entitled "ADDITIONAL INSTRUCTIONS FOR NIH INTRAMURAL PROJECT APPLICANTS"), 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 express/courier service)

At the time of submission, two additional copies of the application must be sent to:

Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda MD 20892-8329 (for U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (express courier)

APPLICATIONS HAND-DELIVERED BY INDIVIDUALS TO THE NATIONAL CANCER INSTITUTE WILL NO LONGER BE ACCEPTED. 

This policy does not apply to commercial courier deliveries (i.e., FEDEX, UPS, DHL, etc.)

(http://grants.nih.gov/grants/guide/notice-files/NOT-CA-02-002.html).  This policy is similar to and consistent with the policy for applications addressed to Centers for Scientific Review as published in the NIH Guide Notice at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-012.html.

APPLICATION PROCESSING:  Applications must be received by the application receipt date listed in the heading of this RFA.  If an application is received after such date, it will be returned to the applicant without review.

ADDITIONAL INSTRUCTIONS FOR NIH INTRAMURAL PROJECT APPLICANTS:

NIH intramural project applicants must use the PHS 398 application form and the modified format and content of Research Plan as specified above with the following additional modifications.

On the Face Page, fill out only items 1, 2, 3 (leave item 3c. blank), 4, and 5.  The remainder of the items should be left blank, AND THE APPLICATION MUST NOT BE SIGNED BY EITHER THE PI OR AN NIH INSTITUTE OFFICIAL.  The RFA label must be affixed to the bottom of the Face Page, as described above in the section entitled "USING THE RFA LABEL."

Do not submit "Other Support," Checklist," "Personnel Report," or "Personal Data" pages.

The PI must obtain the approval of her/his NIH Institute Scientific Director for applying, for collaboration, for participating as a component of the TMEN under the terms and conditions of the RFA, and for complying with the policies of the Steering Committee.  A copy of that letter of approval must be provided as part of a cover letter, addressed to the NCI Referral Officer, for the application.

The budget pages should supply the time and effort information for each project participant, but no other budget figures should be included.  The resources available for the project and the research environment should be carefully described, but no budget figures should be included.  The NIH Institute Scientific Director, as part of the letter of approval for participation, must verify that appropriate intramural resources will be allocated to the project described in the application if it merits funding, and provide assurance that the conduct of the project will comply with the PHS regulations for research involving human subjects (if applicable), with the PHS policy on vertebrate animal research, and with the PHS policies for data sharing and access to research tools.

Submit an unsigned, typewritten original of the application, and five photocopies to:

Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Blvd., Room 8041, MSC 8329
Bethesda MD 20892-8329 (for U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (for express/courier delivery)

Do not send the application or any copies to the NIH Center for Scientific Review.  NIH intramural project applications must be received at the above NCI address on or before the application receipt date described above Section IV.3.A.).  If an application is received after that date, it will be returned to the applicant without review.

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.

The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

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/archive/archive/grants/policy/nihgps_2003/index.htm and at http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.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, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

Section V. Application Review Information


1. Criteria

Only the review criteria described below will be considered in the review process.

The following will be considered in making funding decisions:

2. Review and Selection Process

Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NCI in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

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.

U54 Review Criteria as applicable to this RFA are presented below. (Note: Applications from the NIH investigators will be reviewed for their merits together with applications from extramural investigators using the same set of criteria)

Significance:

Approach:

Innovation:

Investigators:

Environment:

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 the Research Plan, Section E on Human Subjects in the PHS Form 398).

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 E on Human Subjects in the PHS Form 398).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section F of the PHS Form 398 research grant application instructions 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: For U54 applications, the reasonableness of the proposed budget and the requested period of support in relation to the proposed research will be assessed by the reviewers. The priority score should not be affected by the evaluation of the budget.

Institutional Commitments: For NIH intramural project applications, reviewers will assess the adequacy of effort and resources commitments.

2.C. Sharing Research Data

 Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.

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/archive/grants/policy/nihgps/part_ii_5.htm#availofrr and at http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

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 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 (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

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 14 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/archive/grants/policy/nihgps_2003/index.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/archive/grants/policy/nihgps_2003/index.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement (U54), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined above.

2.A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator of an U54 award under this RFA and the PI on an NIH intramural project under the TMEN auspices will have the analogous primary responsibilities in the following areas:

In addition to these responsibilities and obligations, the PIs and their institutions will be accountable for implementing the approved research resource sharing plan and intellectual property plan for their project.  The NCI anticipates that awardees under the auspices of this RFA will develop unique research resources.  Awardees will be responsible for adherence to the policy of the NIH to make available to the public the results and accomplishments of the activities that it funds.

The NCI reserves the right to require the transfer of appropriate reagents, models, and pertinent data that are generated as the result of participation in research supported under these awards to an eligible third party, in order to preserve the data and/or to continue the research.  Third parties supported under these awards must be informed of this right.

Awardees under the auspices of this RFA should obtain appropriate licenses for technologies that are necessary for the conduct of the proposed research. An appropriate statement that the applicant institution is willing to obtain appropriate licenses for technologies that are necessary for the conduct of the proposed research will have to be provided, if the application is selected for funding. 

2.A.2. NIH Responsibilities

An NIH Project Scientist (i.e., the Project Coordinator designated by the NCI) will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

Additionally, an NCI Program Director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The responsibilities of the designated Program Director will include the following activities:

The NCI Program Director may also serve as the NCI Project Coordinator.

The Director, NCI Center for Bioinformatics, will ensure that there are appropriate core services for the integration of data emerging from the TMEN with data from other NCI programs of human cancer research.  Any bioinformatics activities funded on the individual U54 grants or NIH intramural projects will be required to be conducted coordinately with the activities of the NCI Center for Bioinformatics.   

2.A.3. Collaborative Responsibilities

Collaborative Responsibilities

Steering Committee:  The NCI Project Coordinator and a group consisting of two members (the Principal Investigator and another senior Investigator) from each of the funded U54 programs and from each of the NIH intramural programs participating in the TMEN will be responsible for forming a Steering Committee. Steering Committee will be the main governing board of the TMEN, as defined below.

2.A.4. Arbitration Process

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel will be convened composed of three members. one designee of the Steering Committee chosen without NIH extramural staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two. In the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590, annually (http://grants.nih.gov/grants/funding/2590/2590.htm) 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:

Suresh Mohla, Ph.D.
Chief, Tumor Biology and Metastasis Research
Division of Cancer Biology
National Cancer Institute
6130 Executive Boulevard, EPN Room 5038, MSC 7364
Bethesda, MD  20892-7364 (for U.S. Postal Service express or regular delivery)
Rockville, MD 20852 (for express/courier delivery)
Telephone:  (301) 435-1878
FAX:  (301) 480-0864
Email: mohlas@mail.nih.gov

Because of the multi-disciplinary scientific content of the RFA, potential applicants may be referred to additional NCI extramural program staff for further advice and clarification of the intent of the RFA, or for consultation regarding the design and implementation of bioinformatics projects that are intended to coordinate with those developed by the NCI Center for Bioinformatics (NCICB).

Direct questions about intellectual property, technology licensing, data sharing and research tools issues to:

Wendy E. Patterson, Esq.
National Cancer Institute
Technology Transfer Branch
6120 Executive Boulevard, EPS Suite 450, MSC 7182
Bethesda, MD 20892-7182 (for U.S. Postal Service express or regular delivery)
Rockville, MD 20852 (for express/courier delivery)
Telephone:  (301) 435-3110
FAX:  (301) 402-2117
Email:  pattersw@mail.nih.gov

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 delivery)
Rockville, MD 20852 (for express/courier delivery)
Telephone: (301) 496-3428
FAX: (301) 402-0275
Email:  ncidearefof@mail.nih.gov

3. Financial or Grants Management Contacts:

Crystal Wolfrey
Grants Administration Branch 
National Cancer Institute
6120 Executive Boulevard, EPS Room 243, MSC 7150
Bethesda, MD 20892-7150 (for U.S. Postal Service express or regular delivery)
Rockville, MD 20852 (for express/courier delivery)
Telephone:  (301) 496-8634
FAX:  (301) 496-8601
Email:  wolfreyc@mail.nih.gov

Section VIII. Other Information


Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (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 the scientific merit or the priority score.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are: (1) first produced in a project that is supported in whole or in part with Federal funds; and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time, the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh-Dole Act (see the NIH Grants Policy Statement at http://grants.nih.gov/archive/archive/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:
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://www.nih.gov/about/publicaccess/ and view the Policy or other Resources and Tools including the Authors' Manual (http://www.nih.gov/about/publicaccess/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 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. 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 PA 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.


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