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 http://www.cancer.gov/

Title: The Integrative Cancer Biology Program (ICBP): Centers for Cancer Systems Biology (CCSB) (U54)

Announcement Type
This funding opportunity announcement (FOA) is a reissue of RFA-CA-04-013.

Request For Applications (RFA) Number: RFA-CA-09-011

Catalog of Federal Domestic Assistance Number(s)
93.396

Key Dates
Release Date: March 6, 2009
Letters of Intent Receipt Date: May 18, 2009
Application Receipt Date: June 18, 2009
Peer Review Date(s): October-November 2009
Council Review Date: January 2010
Earliest Anticipated Start Date: February 2010
Additional Information To Be Available Date (URL Activation Date): Not Applicable
Expiration Date: June 19, 2009

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
     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

The purpose of this funding opportunity announcement (FOA) is to promote research on cancer as a complex biological system. The specific goal is to develop reliably predictive in silico or computational models of aspects of cancer initiation and progression that would ultimately lead to a better understanding and management of the disease.  To address these goals, the National Cancer Institute (NCI) solicits applications for interdisciplinary Centers for Cancer Systems Biology (CCSB) that will be established within the context of the Integrative Cancer Biology Program (http://icbp.nci.nih.gov/).  The proposed centers must focus on the integration of experimental and computational approaches towards the understanding of cancer biology.   Through this FOA, the NCI intends to enhance the application of computational models and systems approaches to questions of human cancer across the various sectors of the cancer research spectrum, specifically in the areas of: (a) cancer biology; (b) experimental therapeutics; (c) early interventions; and (d) cancer susceptibility.  By utilizing the power and flexibility of mathematical insights and modeling tools, the ICBP is expected to provide scientific understanding that is crucial for linking basic cancer biology and translational/clinical science.  The CCSBs will also develop an integrated educational and training program to enhance and further develop the field.  In addition, the funded centers will act in concert with other centers and NCI programs to advance the mission of the Institute.

This initiative is an open competition FOA and all qualified applicants are invited to apply.  Under the previous ICBP RFA (CA-04-013), six full and three planning centers were funded.  Existing ICBP U54 grantees may apply for the continuation of their centers under this FOA. ICBP U56 grantees may apply as new, U54 applicants.  All prospective applicants are reminded that although the overall theme of this FOA is very similar to the previous issuance, with an emphasis on predictive computational and mathematical modeling, this FOA has modified requirements for center structure. Specifically, there is an explicit emphasis on predictive computational or mathematical modeling. 

For the purpose of this FOA, specific required types of expertise, activities, and thrust of effort needed to pursue the Center’s research objectives are referred to as “components”.  The three components that are required for each proposed CCSB include:

Component 1: Experimental Systems Biology;

Component 2: Mathematical modeling and/or computational simulation; and

Component 3: Education, Training, and Outreach.

All components should be aligned with a common scientific theme of the proposed Center that should be in the broad area of cancer biology ranging from basic research to translational applications.  The research goals are to be addressed through the coordinated interactions of Components 1 and 2 in conducting Center’s research projects. Applicants may propose one broadly defined, overarching research program or multiple smaller circumscribed research projects. All projects proposed must contain joint contributions of Component 1 & 2.

Background

Cancer remains one of the most complex and devastating diseases in terms of both lives affected individually and negative socioeconomic impact on a global scale.  Despite advances in understanding the mechanisms of cancer and progress in its management, we still lack basic knowledge of some of the fundamental processes of the cancerous cell as well as full appreciation of the success and failure of therapeutic and preventive measures.  Indeed, advances in cancer biology and biomedical sciences over the past fifty years have consistently illustrated and highlighted the inherent complexity of this disease.

The complexity of cancer is manifested on a number of levels and across multiple scales.  First, malignant processes lead to profound changes in the genetic and metabolic networks that control the functioning of the cell. In order to fully understand the development and progression of cancer, we must first understand the networks that govern function in the normal human cell and the changes brought about by oncological transformation.  Second, it is now clear that the biology of a tumor depends not only on the characteristics of the malignant cell, but also on the tissue microenvironment and other characteristics of the host in which the tumor exists.  There are critical reciprocal influences among malignant cells, stromal cells, intercellular matrix components, and a host of soluble mediators, some produced locally and some systemically.  Additional complexity derives from the macro-environmental processes and influences such as the immune response that are known to play a critical role in tumor development and rejection. All of these aspects of biology form a complex interplay driving cancer development, and understanding them is critical to successful management of the disease.

Complete understanding of living processes will certainly come first in systems much simpler than human cancer.  It also follows that the ability to model a process requires a certain level of systems understanding.  Examples of first attempts to understand and model mathematically complex phenomena include the circuitry of bacteria, the yeast cell division cycle, and the quantitation of cellular processes such as cell response to stress stimuli. Nevertheless, despite its complexity, cancer is particularly suited to such systems analyses, given the wealth of information about the underlying genetics, cell biology, and cellular interactions.  Indeed, in recent years, the biomedical sciences have undergone a dramatic shift in both the conceptual and technical approaches that can be brought to bear on the complexity of biological problems.  These problems center on the understanding of the behavior of biological systems whose function is governed by the spatial and temporal ordering of multiple interacting components at the molecular, cellular, and organismal levels.  Systems approaches have resulted in recent advances in modeling specific cancer critical processes, such as apoptosis, cell migration, and cycle.

Part of the impetus for systems-scale approaches in cancer rests on recent advances in acquiring data of the necessary quality and quantity to permit systems-wide analysis, including computer-based modeling.  Besides the more established datasets in genomics, proteomics, and metabolomics, other more descriptive data in cell physiology, imaging, and behavior also exist that contribute or reflect cellular transformation.  In addition, technical advances in imaging, nanotechnology, and physical measurements are providing rich new sets of descriptive and quantitative characteristics of the cell and its components.  Other technical advances have allowed for measurements to be made at the level of single molecules or cells in appropriate temporal and spatial scales.  These advances have made it feasible to generate a more comprehensive “parts list” for any organism or disease state.  Indeed, the NCI, along with other institutions, has generated a large amount of data on the cellular and molecular profiles of normal and cancer cells through such programs as Cancer Genome Anatomy Project (CGAP), Mammalian Gene Collection (MGC), the Tumor Cancer Genome Atlas (TCGA), the NCI Nanotechnology Alliance, Cancer Imaging Program, and the Clinical Cancer Proteomics Program.  These programs and other efforts have supplied considerable data on normal and cancer cells.  Thus, among the diseases, cancer is ideally suited for analysis by a systems, or integrative, biological approach.

Along with advances in biology, equal efforts have been made in the area of applied mathematics and computer simulation.  Mathematical models have found extensive use in describing many complex phenomena in such areas as economics, meteorology, social science, and engineering.  Advances have been seen in applied and theoretical dynamical systems, statistical models, differential equations, game theory, and simulations.  In part, these advances have facilitated the adaptation of these modeling approaches to complex problems including the natural sciences.  Together the availability of these large multi-dimensional datasets and modeling frameworks provide the capability to generate predictive comprehensive models of cancer processes.   

The development of testable models is necessary as a framework for further experimentation, data analysis and validation.  In turn, new experimental data will help to refine model development.  Multi-component, interactive processes at the sub-cellular, cellular, tissue, and organ levels should be amenable to modeling and simulation in ways previously limited by the lack of adequate data.  Because this field is still largely undeveloped and underutilized, there is an opportunity to facilitate its development and application to address fundamental questions in cancer biology.  Traditional molecular and genetic approaches, generally reductionist in nature, will continue to be needed and will be critical aspects of the CCSBs.  However, they will need to be augmented with concepts and methods that will enable global data integration and systems analyses.  This will require the involvement of scientists with new areas of expertise, particularly from the computational disciplines of mathematics, engineering, physics, and computer science.  The need for quantitative data will drive the development of new instrumentation and methods, along with efforts in data and model validation and integration.  The organization and representation of these data streams and their relation to preexisting knowledge will require bioinformatics advances, and the development of computer-based cancer biology hypotheses generated by testable models and intra- and inter-cellular simulations will require mathematical expertise, as will the development of new theoretical frameworks.  It is expected that models, software, and data will be shared through an effort coordinated by the NCI benefiting the general cancer research community.

Objectives and Scope:

All applications submitted in response to this FOA must adhere to the overall goal of the CCSBs to address a critical aspect in cancer biology by developing a comprehensive approach integrating  experimental systems biology and mathematical/computational modeling.  Each awarded CCSB will pursue its own central scientific theme. In addition, each CCSB will also function as part of a coordinated network under the broader auspices of Integrative Cancer Biology Program. The ICBP Steering Committee will oversee the scientific and administrative activities of the CCSB Consortium, consistent with the terms and conditions of the CCSB awards  (for details see Section VI.2 of this FOA).

All applicants must address the following elements:

  1. Scientific theme for the Center within the broad area of cancer biology;
  2. Leadership and coordination of Center efforts (Administrative Core);
  3. Research Program (defined by Components 1 and 2 outlined below); and
  4. Education, Training, and Outreach program for the Center (defined by Component 3 outlined below).

1. Scientific Themes for the Proposed Centers.

It is critical for the proposed CCSBs to include interdisciplinary teams of researchers from an appropriate spectrum of fields, including for example biology, mathematics, imaging, engineering, technology, bioinformatics, and computational modeling.  Each team must be focused on understanding and generating predictive models of specific cancer processes.

The proposed CCSBs are expected to focus on key problems in the broad area of cancer biology that may range from fundamental basic research questions to areas with important translational impact.  Examples of specific mission critical areas that may serve as center themes include but are not limited to the following:

2. Leadership and Coordination of Center Efforts (Administrative Core).

Organizing multiple projects (or one large, complex project), incorporating diverse approaches, and recruiting and training personnel, is a complicated process.  Projects must integrate multi-investigator, multi-disciplinary approaches with a high degree of interplay between cancer biological experimental approaches and computational and theoretical approaches. 

An appropriate Administrative Core must be proposed to define the coordination of Center functioning. CCSB applicants must propose specific leadership and organizational structures and plans to facilitate the integration of all the Center efforts.

Each center should also form an External Advisory Panel (EAP) to include three to five experts in the areas currently being addressed within the centers.  This panel is primarily designed to provide feedback and suggestions to the individual centers and should therefore interact with the center at least once a year.  The Administrative Core will coordinate the interactions between the EAP and the CCSB.

3. Research Program (Projects) reflecting integrated effort of Experimental Systems Biology and Computational Biology: Mathematical Modeling and/or Computer Simulation (Components 1 and 2, respectively)

CCSB applicants may propose either (a) one broadly defined, overarching research project or (b) two to three smaller, circumscribed research projects. All these research efforts must reflect coordinated interaction of Components 1 and 2. Regardless of the specific approaches, and center organization, efforts of both components must be integrated with the goal to develop predictive computational models and to test them experimentally in a highly iterative fashion.

Component 1 -- Experimental Systems Biology

The Experimental Systems Biology component must focus on the complex interactions in biological systems, employing an integrative approach (as opposed to a reductionist approach that typifies most biological studies).  This integrative approach necessitates an examination of numerous aspects of a system in order to identify and characterize the various interactions and network logic of a system.  This knowledge of a system can be extrapolated to predicting system behavior.  A systems approach aims to describe not only interactions within a single dynamic system, but interactions of networks that develop across various scales, and/or evolve over time.  To this end, it is imperative to generate detailed experimental data about the system or disease areas.  In the past, the available datasets have been derived from large “omic” analyses of DNA polymorphisms, gene expression profiling, proteomics, etc.  Whereas these types of datasets are comprehensive within a given parameter, they do not fully describe cellular behavior.  Applicants responding to this FOA are encouraged to incorporate multi-parametric approaches and to consider also non-traditional types of data (for example, descriptive and qualitative parameters).  The choice of data type(s) should be driven by the biological question and modeling approach to be employed.  The issue of sufficient “depth” of data may be addressed “horizontally,” reflecting numerous data points of a specific type of measure (such as all kinases or cell types in a given environment) or “vertically,” reflecting numerous data from diverse types of measure, such as proteomic and cellular phenotypes.  Independent of the source of the “parts list” in a systems biology approach, the data should be well integrated as to address the complexity of the cancer system being studied.

The activities related to Component 1 must include collaborative efforts on experimental testing and refining of predictive computational models related to Component 2 (see below). 

Component 2 – Computational Biology: Mathematical Modeling and/or Computer Simulation

The second critical approach to be used by the CCSBs is mathematical modeling and/or computational simulation of the fundamental biological processes.  Mathematical modeling involves the use of mathematical equations and relationships to represent biological phenomena.  Complementary to this type of modeling is the use of computer simulations to represent these modeling approaches.  These approaches serve two purposes.  First, they provide a basic framework for the interrogation and integration of data, often providing insight into the type and quality needed for addressing a hypothesis or experimental design.  This feature is especially useful when trying to integrate or analyze the large datasets generally associated with systems biology.  Second, and more important, these models or simulations should allow one to predict the biological state under investigation and predict how the natural process will behave in various circumstances.  It is often easy to vary parameters in the mathematical model over wide ranges, whereas this may be very time consuming or expensive, if not impossible, in an experimental setting.  Indeed, the appropriate computational model can be used as an initial test of a new biological hypothesis concerning cancer biology or make predictions or recommendations concerning an area of treatment.  Similar to a variety of data types, there are a number of currently utilized mathematical modeling approaches, including deterministic models utilizing discreet equations to describe physical reactions and probabilistic models frequently incorporating stochastic simulation and statistical models.  The choice of a modeling strategy is expected to depend on the question to be addressed and the data to be utilized.  Applicants should select appropriate modeling approaches and mathematical tools and provide justification for their selections.  Along with the application of appropriate modeling tools, this FOA encourages further exploration and research in this component of the center.

Pilot Research Efforts

Given the overall purpose of the ICBP to advance the field of systems biology and modeling, CCSBs will be encouraged to explore new opportunities by supporting small innovative pilot projects.   Therefore, flexibility in reallocation of center resources as well as new supplemental funding is expected It is envisaged that each funded Center will identify new opportunities and pursue new theories, ideas, and approaches aligned with the scope of the center. 

4. Education, Training, and Outreach Program (Component 3)

Training of professionals well-versed in bioinformatics and mathematical modeling, and having a deep understanding of the biology of cancer, is critical for current and future progress of the field.  Thus, all the applicants responding to this FOA must propose appropriate educational programs, both internal to the individual CCSBs and external to the greater scientific community.  These educational activities may range from formal undergraduate, graduate, and post-graduate programs to courses and seminars for students and working researchers, visiting-scientist programs, 1- to 2-week-long intensive training programs, and other innovative programs to help spread the knowledge and resources generated.  These educational programs must also help integrate the various scientific disciplines of the individual CCSB.  The Centers will be expected to help “seed” the greater scientific community by disseminating expertise and knowledge, for example, through workshops and/or symposia.  Because the Centers will be pioneering new directions in biological sciences, the CCSB applicants are expected to plan for outreach activities to both traditional and non-traditional research institutions.

The overall proportion of the center effort dedicated to training/outreach activities may vary but should be well justified based on the unique strengths of the applicant team and the scientific profile of the proposed Center.

Other Related Funding Opportunities:  Besides the CCSB applications solicited by this FOA, investigators interested in the ICBP but preferring smaller projects may consider an alternative ICBP-related FOA (PAR-09-026), “Collaborative Research in Integrative Cancer Biology and the Tumor Microenvironment (U01),” which involves use of the U01 funding mechanism.  Prospective applicants should note, however, that PAR-09-026 requires collaborative participation of investigators, who are already affiliated with another ICBP award.

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

Section II. Award Information


1. Mechanism of Support

This funding opportunity will use the NIH Specialized Center Cooperative Agreement (U54) award mechanism(s).

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). 

This funding opportunity will use a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) 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 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.

3. Other-Special Eligibility Criteria

Resubmissions. Resubmission applications are not permitted in response to this FOA.

Renewals. Renewal applications are permitted but only for U54 awards funded under the RFA-CA-04-013, Integrative Cancer Biology Program. Note that these renewal applications will be subject to evaluation using additional Review Criteria relative to new applications (see Section V of this FOA).  U56 awardees under the RFA-CA-04-013 must apply as new applicants.

Number of Applications. Applicants may submit more than one application, provided each application is scientifically distinct.

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 current PHS 398 research grant application instructions and forms with the exceptions noted below.  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 in item (box) 2 only of the face page of the application form and the YES box must be checked.

Applicants must demonstrate in the application their ability to meet:

Instructions for the Preparation of CCSB Applications

RESEARCH PLAN: The standard PHS398 Research Plan (Items 2-5 as per Revision 11/07 of the PHS 398 Table of Contents, previously known as “Sections A-D”) is altered as follows:

Specific Sections to be included in Research Plan are described below. (Table of Content should be modified accordingly).

Section N1:  Center Overview and Effort Integration

This section should provide an overview of the entire proposed center including scientific focus, overview of Center components, their integration, and a proposed timeline for the overall 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 proposed projects will be inter-disciplinary and will draw on a variety of resources.  Thus, a well thought out and carefully described organization is required.  The Center PI and project lead investigators will be 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.  The efficient coordination of these efforts will be particularly important for multi-institutional programs.  The management plan should clearly outline the organization and administration of the proposed center.

The U54 grant application should specify the administrative and organizational structure(s) that will be used to support the research.  Projects with the complexity, both scientific and managerial, that NCI anticipates will characterize these Centers will require a substantial amount of the PIs’ effort to achieve success.  Therefore, each PI will be expected tto devote at least 25% effort to the leadership and implementation of the Program.  If well justified, an investigator may be lead investigator of more than one project including the overall Center PI.  To provide the necessary interdisciplinary perspective and insights, the lead investigators must demonstrate distinct areas of expertise for their Center responsibilities.  If additional core facilities or shared resources are required, these should be described, as should their management and service to the research projects. 

The applicant should explain how different elements of the organization, including key personnel, will interact, why they are essential to accomplishing the research, and how the combined resources create capabilities that are more than the sum of the parts.  "Centers-without-walls" or multi-institutional programs are welcome under this solicitation.  If any of the elements are physically separated from each other (i.e., located in different departments or institutions), the applicant should address how interactions will be facilitated.  Within the confines of the above specifications, the NCI is not specifying a defined organizational structure, allowing applicants to develop the structure that would best promote their research.  However, applicants should note that the effectiveness of the proposed structure will be a criterion of the evaluation prior to an award and will be monitored after an award is made.  It is essential that the center proposed have strong well-integrated programs of cancer biology and in silico modeling.  In addition, these areas should be balanced in effort.  Each component should not only apply current approaches, but develop new insights in keeping with the overall mission of the Center and the ICBP consortium.

Section N2:  Administrative Core

It is expected that each Center will organize an administrative core. Summarize in this section the proposed administrative structure for the Center, concisely defining the leadership structure and propose specific activities to coordinate Center’s efforts. Interaction with ICBP Steering Committee should also be described. In addition, relationships between the proposed Center and other research, academic, and administrative units of the applicant institutions and the central administration should be described in this section.

This section should also describe the structure and function of the External Advisory Panel. 

Section N3:  Preliminary Results/Progress Report

For new applications (applicants with no previous ICBP grant support and current ICBP U56 awardees), this section should include preliminary results that demonstrate progress in both experimental and computational approaches proposed to be carried out in the center.  It should also describe existing education and outreach activities being conducted by the applicant hat relate to the goals of the CCSB.

For renewal (competing continuation, U54 ICBP awardees) applications, this section should provide a description of the progress made during the last funding cycle.  It should briefly state the goals of the previous funded project along with a report on the major accomplishments of the Center and should address progress in each of the original Program goals.   

Section N4:  Research Program (integrated research effort of Components 1 and 2).

This section should include a detailed research plan for either: (a) one broadly defined, overarching research program or (b) multiple smaller circumscribed research projects (comparable in scope to a typical R01 project). Applicants should realize that larger number of projects may not necessarily be advantageous and that all the proposed elements of their research program/projects should be cohesive and scientifically comparably well developed. All projects must be well justified in the context of the scientific theme of the proposed Center.

Describe each research program (or projects) in sufficient detail to enable reviewers to judge their scientific merit. All research programs/projects must reflect coordinated interaction of Components 1 and 2 and must focus on predictive computational models and their experimental testing.

Each Research Project must contain the following elements:

Project Face page containing project title, name of Project Leader, Project Summary and Key Personnel (listing percent of effort of each individual); and Research Plan (analogous to Standard items 2-5 in the PHS 398 instructions).

Optional Element – Shared Resources Core(s). Depending on specific needs, one or more research support cores may be proposed. These cores must not duplicate analogous resources already established in the applicant institutions (although supplemental funding to such existing resources may be requested).

Pilot Research Efforts. Each awarded CCSB will be expected to pursue new opportunities pertinent to the scientific theme of the Center. In this section, describe briefly (under a separate heading) how potential pilot projects will be identified, prioritized and administered. (Specific pilot projects need not be identified in the CCSB applications.) 

Section N5:  Education, Training, and Outreach Program (Component 3)

This section should include a description of all activities planned for education, outreach, and training in support of the overall goals of the center including a description of how these activities will enhance the CCSB and benefit the larger cancer systems biology community.  This description should highlight unique opportunities available at the applicant institution and opportunities for leveraging the expertise and research program/projects of the proposed Center.

Additional information is available in the PHS 398 grant application instructions.

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: May 18, 2009
Application Receipt Date: June 18, 2009
Peer Review Date: October-November 2009
Council Review Date: January 2010
Earliest Anticipated Start Date: February 2010

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 NCI 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:

Daniel Gallahan, Ph.D.
Division of Cancer Biology
National Cancer Institute
6130 Executive Boulevard, EPN
Room 5050, MSC 7380
Bethesda, MD 20892
Telephone: (301) 496-8636
FAX: 301-496-8656
Email: gallahad@mail.nih.gov

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 (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 regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-3428

FAX: (301) 402-0275
Email: ncirefof@dea.nci.nih.gov

3.C. Application Processing

Applications must be received on or before the application receipt date 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 or renewal award if such costs: 1) are necessary to conduct the project; and 2) would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or renewal award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the Center (see NIH Grants Policy Statement at http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

6. Other Submission Requirements and Information

Awardees must agree to the “Cooperative Agreement Terms and Conditions of Award” in Section VI2.A “Award Administration Information.”

Site Visits and ICBP Meetings. Because of the complexity and interactions of the CCSBs, NIH/NCI program staff members will conduct administrative site visits.  It is expected that two site visits will be made during the course of the award at mutually agreeable times.  If deemed necessary by NCI staff, additional site visits may be made.  In addition to the site visit, the principal investigators along with key center staff must agree to participate in two annual ICBP meetings of all the funded CCSBs.  The ICBP meetings will be used to assess progress, disseminate knowledge, models, and tools, and to allow for direct interaction of the CCSBs.  Appropriate center staff will also be expected to participate in specialized ICBP group activities, teleconferences, and meetings when appropriate.  While some additional travel funds are expected to be available, Centers should be prepared for scheduled visits and should budget appropriately (including travel for collaborators and other necessary costs).

External Advisory Panel (EAP).  Each center should also form an External Advisory Panel (EAP) to include three to five experts in the areas currently being addressed within the centers.  This panel is primarily designed to provide feedback and suggestions to the individual centers and should therefore interact with the center at least once a year.  The selection of the EAP is to be made by the PIs with consent from the NCI program officer.  The applicants are expected to identify the desirable profiles of prospective EAP members. However, to facilitate application review, the applicants must refrain from identifying the names of specific individuals in their application and must not contact such candidates.

ICBP Steering Committee

An ICBP Steering Committee, consisting of representatives from all funded CCSB, will be formed to provide overall leadership of the ICBP.  Details on the composition and responsibilities of the Steering  Committee are defined in Section VI.2.A of this FOA under “Cooperative Agreement Terms and Conditions of Award.”

Participation in evaluation activities.

Each center award and the entire ICBP program will be periodically evaluated by the NIH. Applicants should acknowledge their readiness to participate in such evaluation.

Research Plan Page Limitations

The PHS 398 standard page limit for Items 2-5 is replaced by a new limit of 60 pages for the new Sections N1 through N5.

Appendix Materials

All paper PHS 398 applications must provide appendix material on CD only, and include five identical CDs in the same package with the application (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html).

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: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact.  See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible.  A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (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/.

In addition to the stated above NIH-wide requirements, applicants responding to this FOA must agree to the following requirements:

Plan for Sharing Research Data, Software, and Models:

The NCI is committed to the principle of rapid data and software release to the scientific community.  CCSB awardees are expected to release their data and software in a timely fashion through publicly available databases or other standard mechanisms whenever possible.  It is recognized, however, that standards and methods for model sharing and standards and methods for sharing of less common forms of data are currently lacking.  The development of policies, methods, and standards for model sharing are critically important for the ICBP (e.g., new mechanisms for sharing of less common forms of systems biology data and software).  NCI expects that the ICBP Steering Committee will develop such policies, methods, and standards for the ICBP Consortium.  NCI further expects that any such policies, methods, and standards will remain consistent with NIH-wide policies on data and resource sharing.

In their grant applications, all applicants should provide specific plans for data and software release.  Applicants should also indicate their willingness to abide by the data, software and model release policies that are expected to be developed by the ICBP Steering Committee, to the extent these policies are consistent with the goal’s of the ICBP program, the applicant’s plans for data and software release, and applicable grant regulations.

The reasonableness of the applicant’s data sharing and software release plan will be assessed by the reviewers.  However, reviewers will not factor the proposed data sharing and software release plan into the determination of scientific merit or the priority score.  

After completion of the initial review, NCI program staff will be responsible for any additional administrative review of the data sharing and software release plan.  The adequacy of the data 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 sharing and software release plan with the prospective awardee before recommending funding of an application.  The final negotiated version of the data sharing and software release plan will become a condition of the award of the cooperative agreement.  The applicant’s progress in implementing the data sharing and software release plan will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590).  See Section VI.3. Reporting. 

Section V. Application Review Information


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 mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability.  As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system. 

Overall Impact. Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Center to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five core review criteria, and additional review criteria (as applicable for the Center proposed). 

Core Review Criteria.  Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each.  An application does not need to be strong in all categories to be judged likely to have major scientific impact.  For example, a project that by its nature is not innovative may be essential to advance a field.

Significance.  Does the Center address an important problem or a critical barrier to progress in the field?  If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved?  How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

In addition, specific to this FOA:

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the Center (if applicable)?

In addition, specific to this FOA:

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?

Approach: Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Center?  Are potential problems, alternative strategies, and benchmarks for success presented?   If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment:  Will the scientific environment in which the work will be done contribute to the probability of success?  Are the institutional support, equipment and other physical resources available to the investigators adequate for the Center proposed?  Will the Center benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?   

NIH considers the following in evaluating Center grant applications:

In addition to the above review criteria, the following criteria will be applied to applications in the determination of scientific merit and the priority/impact score.

1) Performance/Progress (Type 2 renewal applications only from current U54 ICBP awardees):

2) Center Integration/Administrative Core

3) Research Program/Projects

4) Education, Training, and Outreach Program

Is the training and outreach plan appropriate, i.e., is it likely to meet the needs of the Program and the scientific community in cancer and systems biology?  Does it integrate well with and leverage existing educational and training resources at the institution(s)?  Will this Center serve as a model for cross-disciplinary activities?

Additional Review Criteria.  As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, but will not give separate scores for these items.

Protections for Human Subjects.  For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects  and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

Inclusion of Women, Minorities, and Children.  When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

Vertebrate Animals.  The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia.

Renewal Applications.  When reviewing a Renewal application (formerly called a competing continuation application), the committee will consider the progress made in the last funding period.

Biohazards.  Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Additional Review Considerations.  As applicable for the project proposed, reviewers will address each of the following items, but will not give scores for these items and should not consider them in providing an overall impact score.

Budget and Period Support.  Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Select Agent Research. Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans.  Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable:  1) Data Sharing Plan (http://grants.nih/gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

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/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 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 Center as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

These Terms and Conditions of Award apply to all individual CCSB U54 awards.  All the awardee institution(s), principal investigators (PIs/PDs) and other key personnel must agree to collaborate on the goals of the over arching ICBP Initiative.

2. A.1. Awardees and Principal Investigators Rights and Responsibilities

The Principal Investigators will have the primary responsibility for:

Specific rights and responsibilities of CCSB awardees will include the following:

2. A.2. NIH Responsibilities

NIH program directors, acting as Project Scientists, will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

The main NCI staff members’ responsibilities pertinent to the CCSB U54 awards include the following activities:

The NIH Project Scientists will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications.  If such participation is essential, these individuals will seek NCI waiver according to the NIH procedures for management of conflict of interest, as implemented by NCI.

Additionally, an NCI Program Director acting as the Program Official will be responsible for the normal scientific and programmatic stewardship of the awards and will be named in the award notice.  A Program Official may also have substantial programmatic involvement (as a Project Scientist).  In that case, the individual involved will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications, or will seek NCI waiver.

2.A.3. Collaborative Responsibilities

An ICBP Steering Committee will oversee the scientific and administrative activities of the CCSB Consortium.  The ICBP Steering Committee will be jointly established by all the awarded Centers and involved NCI program staff members (i.e., Project Scientists).  The ICBP Steering Committee will consist of: (a) two representatives of each awarded Center (typically PD/PI and other designated senior investigator); and (b) two NCI Project Scientists.  The organizational structure is designed to allow NCI program staff to facilitate and promote inter-Center collaboration pilot projects based on synergistic Center projects.

Each full member of the Steering Committee will have one vote.

In addition, the designated NCI Program Director serving as a Program Official will participate in the activities of the ICBP Steering Committee as a non-voting member.

All ICBP Steering Committee decisions and recommendations that require voting will be based on a majority vote.

The ICBP Steering Committee will have primary responsibility for the overall organizational oversight of the CCSB Consortium and for reviewing the research goals among the Centers.

Responsibilities of the ICBP Steering Committee will include the following:

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 composed of three members will be convened.  It will have three members: a designee of the Steering Committee chosen without NIH 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 Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

Section VII. Agency Contacts


We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.  Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

Daniel Gallahan, Ph.D.
Division of Cancer Biology
National Cancer Institute
6130 Executive Boulevard, EPN Room 5050, MSC 7380
Bethesda, MD 20892-7380
Telephone: (301) 496-8636
FAX: 301-496-8656
Email: gallahad@mail.nih.gov

2. Peer Review Contacts:

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 regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-3428
FAX: (301) 402-0275
Email: ncirefof@dea.nci.nih.gov

3. Financial or Grants Management Contacts:

Crystal Wolfrey
Office of Grants Administration
National Cancer Institute
6120 Executive Boulevard, EPS Suite 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: 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); 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 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/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 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. 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 two years to the research. For further information, please see: http://www.lrp.nih.gov.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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