RFA-CA-08-005: Advanced Genomic Data Analysis and Visualization Methods for the Cancer Genome Atlas (TCGA) Data (R21)

Department of Health
and Human Services (HHS)

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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: Advanced Genomic Data Analysis and Visualization Methods for the Cancer Genome Atlas (TCGA) Data (R21)

Announcement Type

New

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least 4 weeks prior to the grant submission date. See Section IV.

Request For Applications (RFA) Number: RFA-CA-08-005

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

Key Dates
Release/Posted Date: August 28, 2007
Opening Date: November 10, 2007 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date: November 10, 2007.
NOTE: On-time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization).
Application Submission/Receipt Date: December 10, 2007
Peer Review Date(s): February/March 2008
Council Review Date: May 2008
Earliest Anticipated Start Date: July 2008
Additional Information To Be Available Date (Activation Date): Not Applicable
Expiration Date: December 11, 2007

Due Dates for E.O. 12372

Not Applicable.

Additional Overview Content

Executive Summary

This NCI-sponsored funding opportunity announcement (FOA) is a request for grant applications that describe exploratory projects aimed at the development of highly innovative and novel advanced genomic data analysis methods and visualization technologies. This FOA is a component of The Cancer Genome Atlas (TCGA; http://cancergenome.nih.gov) Pilot Project, which tests the technical feasibility and clinical relevance of conducting a systematic, comprehensive large-scale analysis of genomic alterations found in human cancers.
The purpose of this FOA is to stimulate the development of new and improved computational and statistical tools for integrative analysis of the TCGA data sets covering alterations in the cancer genome, epigenome, and/or transcriptome (e.g.,somatic mutations, changes in DNA segment copy number, translocations, loss of heterozygosity, epigenomic modifications, and gene expression profiles from multiple platforms) and linked pathological/clinical information. Of particular interest is the development of tools and methods for analyzing, mining, and visualizing TCGA data to reveal previously unknown associations between genomic alterations, pathways, and cancer. Proposed projects should facilitate extensive evaluation and visualization of molecular changes that occur in human cancer through cross-domain queries to interrogate diverse sets of genomic data as well as clinical, laboratory, and pathology data from patients. All projects must adhere to the cancer Biomedical Informatics Grid (caBIG) standards.
Mechanism of Support. This FOA will utilize the NIH R21 award mechanism for pilot exploratory research projects.
Funds Available and Anticipated Number of Awards. NCI intends to commit approximately $2,000,000 in FY 2008 to fund six to ten new grants in response to this funding opportunity.
Budget and Project Period. The total project period for an application submitted in response to this FOA may not exceed 2 years. Direct costs are limited to $275,000 during a 2-year funding period, with no more than $200,000 in direct costs allowed in any single year.
Eligible Institutions/Organizations. Public/State Controlled Institution of Higher Education; Private Institution of Higher Education; Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education); Nonprofit without 501(c)(3) IRS Status (Other than Institution of Higher Education); Small Business; For-Profit Organization (Other than Small Business); State Government; U.S. Territory or Possession; Non-domestic (non-U.S.) Entity (Foreign Organization); Eligible agencies of the Federal government.
Eligible Project Directors/Principal Investigators (PDs/PIs): Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
Number of Applications. Applicants may submit more than one application, provided each application is scientifically distinct.
Application Materials. See Section IV.1 for application materials.
Renewals and Resubmissions. Neither renewals nor resubmissions are allowed for this FOA.
Number of PDs/PIs. More than one PD/PI, or multiple PDs/PIs, may be designated on the application.
General Information. For general information on SF424 (R&R) Application and Electronic Submission, see these Web sites:

SF424 (R&R) Application and Electronic Submission Information: http://grants.nih.gov/grants/funding/424/index.htm
General information on Electronic Submission of Grant Applications: http://era.nih.gov/ElectronicReceipt/

Hearing Impaired. Telecommunications for the hearing impaired is available at: TTY 301-451-5936.

Exceptions:

All applicants must include a Data Sharing Plan and a Resource Sharing Plan in their application.

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

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

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2. Cost Sharing or Matching
3. Other - Special Eligibility Criteria

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

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
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

PURPOSE

This funding opportunity announcement (FOA) is part of The Cancer Genome Atlas (TCGA; http://cancergenome.nih.gov/) Pilot Project, which is a collaborative effort between the National Cancer Institute (NCI) and National Human Genome Research Institute (NHGRI). The overall goal of the TCGA initiative is to enhance the overall and specific understanding of genomic alterations associated with the initiation and pathological progression of human cancers. The TCGA Pilot Project is exploring the feasibility and benefits of a large-scale systematic effort to rigorously and comprehensively characterize molecular alterations of specific tumor types and sub-types.

As a component of the TCGA initiative, this FOA solicits applications for research projects aimed at the development of highly innovative computational analysis and visualization tools for the characterization and integrative analysis of large, complex genomic datasets arising from different technology platforms.

This FOA is designed to support the development of new analytical methods and visualization technologies pertinent to TCGA-generated data. The main desired attributes of such tools include:

(i) Robust and reproducible detection of patterns reflecting changes in the cancer genome, epigenome, and/or transcriptome and relating those patterns to the linked pathological/clinical data; and

(ii) Greater specificity, sensitivity and accuracy than current technologies.

Definitions. In the context of this FOA, the terms analyses and analytical methods refer to computational methods used to evaluate data generated during the TCGA project, i.e., data derived from the cancer genome and/or epigenome and/or transcriptome, and/or DNA sequences along with underlying pathological/clinical data as well as analogous data sets for matched normal clinical samples. The term visualization encompasses methods that enable researchers to integrate data generated by various platforms into interpretable graphical formats that facilitate the understanding of the results. Analytical methods and visualization technologies include, but are not limited to, techniques and software applications. The term genomic level in expressions such as genomic level alterations is used in a broader sense to encompass not only DNA sequences/variants but also changes in epigenomic and transcriptomic aspects as well.

Main Required Characteristics of the Solicited Projects. Technologies and methodologies solicited include those that are suitable to identify and extract patterns from comprehensive genomic level data that would help determine and/or predict relationships between defined genomic level parameters and pathological/clinical data. These technologies and methodologies should be designed to integrate and analyze the data in a fashion that would yield new insights into the relationships among the different data components (e.g., those relating to clinical information, gene expression, methylation patterns, and DNA sequences).

In addition, TCGA data are being made available through infrastructure that adopts standards defined by the cancer Biomedical Informatics Grid (caBIG) program (https://cabig.nci.nih.gov). Tools developed under this FOA are expected to take advantage of the caBIG infrastructure where appropriate, and to conform to caBIG standards and principles.

To meet the goals of this FOA, applicants should focus on approaches that increase the ability to examine genomic level data generated from multiple platforms that are integrated with pathological/clinical data in a given dataset, so that reliable and informative analyses can be performed to yield new insights into cancer biology. Significant improvements of current integrative genomic level data analysis methodologies and visualization technologies will also be considered. For example, technologies that enable novel pattern recognition from large datasets or that employ novel data mining procedures would be appropriate.

This FOA is not intended to support projects focused on databases, data curation, and basic analysis methods. Applications for the development of such tools and methods will not be considered responsive and will be returned to applicants without peer review.

Also, this FOA will not support projects addressing the basic analysis of genes, genomic sequences, other regions of the genome or transcriptome, proteins or peptides, clinical correlative studies of biomarkers, or hypothesis-driven analysis that are primarily oriented toward the understanding of the roles of specific genes and/or gene products in cancer.

BACKGROUND

Cancer is a complex and heterogeneous disease whose initiation and pathological progression are influenced by a variety of molecular changes, including chemical alterations to nucleic acids, proteins, and other biomolecules. The complete characterization of the genomic changes that distinguish any particular cancer type may, therefore, help to predict the pathologic behavior of that cancer as well as its responsiveness to particular modes of treatment. Such knowledge signifies the potential for a better understanding of cancer biology and aids in the accelerated discovery of new tools and biomarkers for detection, diagnosis, treatment, and prevention. This knowledge may also lead to the identification of new targets for therapeutic intervention and a refined clinical understanding of patient stratification in cancer therapy. Thus, further progress in innovative technologies for molecular feature detection and characterization is crucial to the emergence of new directions and paradigms in cancer research.

Among the molecular alterations that occur in the pathogenesis of cancer are an increasing number of somatic mutations. Inherited genetic variants can also contribute to cancer susceptibility. Understanding these cancer-associated mutations provides important insights into the molecular processes underlying the development and progression of certain tumors. Moreover, encouraging clinical results with drugs designed to directly target protein products of cancer-associated and altered genes have provided proof-of-principle that these alterations identify valuable targets for drug therapy.

Given the complexity and heterogeneity of cancer, it is generally believed that only a fraction of the alterations that may be useful as characteristic markers of specific tumor types and/or potential molecular targets have been identified to date. Consequently, one of the major hurdles in conducting a comprehensive genomic level analyses of cancer will be to overcome the limitations of current technologies in the examination of complex and heterogeneous tumor specimens as well as the various types and subtypes of cancer. Examples of limitations include, but are not exclusive to, the ability to: comprehensively identify all of the transcripts and their variants in cancer cells; determine the boundaries of amplified or deleted regions; identify molecular networks that are important in cancer progression; and relate specific identified molecular changes to concrete and meaningful clinical parameters. Such limitations must be overcome if the identification of all genomic level alterations that contribute to cancer pathology and/or susceptibility is to be successful. TCGA projects (especially those from this particular FOA) are designed to directly address these limitations.

Overall Objectives of The Cancer Genome Atlas Pilot Project. In 2005, the NCI and the NHGRI announced a joint effort to pursue a pilot project to determine the feasibility of identifying and cataloging the genomic level alterations associated with human cancers. This pilot project is focused on three tumor types with the goal of assessing the technical feasibility and clinical relevance of conducting a comprehensive analysis of cancer-associated genomic level alterations. The three tumor types are: glioblastoma multiforme, squamous cell lung carcinoma and serous cystadenocarcinoma of the ovary.

The comprehensive genomic level data generated by this pilot project (including DNA sequence variants, DNA segment copy number alterations, epigenomic and transcriptomic changes), combined with the clinical information about the cancer samples, will provide the initial contribution to a comprehensive resource that describes the genomic fingerprints associated with specific cancer types. This resource will be known as The Cancer Genome Atlas (TCGA;
home page: http://cancergenome.nih.gov; data page: http://tcga-data.nci.nih.gov).

The TCGA Pilot Project is designed to verify:

(1) whether or not genes and other defined types of genomic regions contributing to cancer causation, pathology, and/or susceptibility can be comprehensively identified by combining information from diverse approaches to genome analysis, including transcription profiling, methylation analysis, and copy number alteration analysis; and

(2) whether or not the large-scale genomic level characterization and sequencing can be efficiently and cost-effectively achieved.

TCGA Data Coordinating Center (DCC) is using caBIG-compatible infrastructure to host and distribute the data. Data standards adopted by caBIG include both structural and semantic specifications. Thus, the use of TCGA data should be straightforward to scientists who are not currently involved in the program. In addition to bulk data downloads, the DCC's caBIG data systems provide dynamic access to data through well defined application programming interfaces (APIs). These APIs can be leveraged to interrogate and retrieve subsets of data, and to correlate data from one resource with data from others.

OBJECTIVES AND SCOPE

As a TCGA component, this FOA seeks to broaden the involvement of computational scientists in TCGA and have them apply their expertise to develop novel approaches to data analysis and visualization of genomic level alterations that are relevant to the TCGA Pilot Project. Whereas high-throughput, cost-effective technologies to survey specific types of genomic level alterations exist, there is a great need for significantly improved methods to perform cross-platform analyses on genomic level alterations through unbiased, unsupervised queries. There is also a need for meta-analysis tools that would perform integrative analysis of genomic level alteration data derived from different platforms with clinical and non-genomic data.

Projects proposed for this FOA should be designed to identify and overcome the critical limitations of current basic genomic level analysis methods. These projects must be directly applicable to the TCGA data collected from various genomic level analysis methods (sequence variants, copy number and/or epigenomic changes, expression profiling) along with associated pathological/clinical data for the biospecimens (http://tcga-data.nci.nih.gov/tcga/findArchives.htm). It is thus crucial that computational analysis methods and visualization technologies proposed for support under this FOA achieve the level of performance required for the characterization of large, complex datasets that contain various types of genomic level data and linked pathological/clinical, information.

Priorities of this FOA. Projects sought must center on the development of novel or significantly improved analytical methods or visualization technologies that would be suitable for large, complex datasets. Potential applicants should consider in particular innovations in analysis methods and visualization technologies aimed at:

reducing bias introduced into analysis methods and visualization technologies (e.g., by improving approaches to formulating unsupervised queries to replace subjective, human intelligence-driven queries);
integrating various types of data;
enhancing the analysis and visualization of numerous types of genomic and clinical data;
integrating statistical analytical methods with meta-data analysis;
increasing the comprehensiveness of genomic level analyses; and
increasing sensitivity and specificity.

Examples given below are only illustrative of the types of capabilities that are of interest for the analyses of datasets generated from TCGA’s large-scale characterization of cancers, their genomes (chromosomal segment copy number alterations and sequence variants), epigenomes, and/or transcriptomes. Applicants are expected and encouraged to propose integrative analysis methods that take advantage of and utilize several or, ideally, all TCGA data types. The following list is not intended to be all-inclusive:

Mapping possible connections between expression, sequence, and/or clinical data patterns (from multiple pathological and normal samples) and specific metabolic and signaling pathways;
Top-down or bottom-up successive clustering of data from multiple platforms. (In a top-down approach, an overview of the system is first formulated, specifying but not detailing any first-level subsystems. In a bottom-up approach, the individual base elements of the system are first specified in great detail);
Temporal cause-and-effect relationships between genes and pathways;
Prediction of gene expression patterns based on the statistical analysis of TCGA datasets and the identification of transcripts that deviate from the predicted normal pattern;
Identifying non-serial linkage and/or networks between groups of genes, pathways or genomic regions based on partition clustering of clinical and genomic level data; and
Finding correlations between specific expression patterns (and/or other genomic level data) and distinct clinical stages or aspects of a cancer (e.g. correlation with age at cancer onset, cancer subtypes, etc.)

Applicants should include a description of plans for the specific data types that will be handled, the types of methods that will be applied, and the software tools or resources that will be produced.

A description must be provided of how caBIG systems will be accessed and used to advance the proposed project. If a new software tool is being proposed, a description of how caBIG standards and compatibility will be incorporated is required.

This FOA will NOT support efforts in the following areas:

Data management, data warehouse, and related technologies (as applicants are expected to use caBIG infrastructure for these needs);
Workflow engines, analysis pipeline construction tools;
Point solutions or methods for analyzing a single data type (i.e., methods that do not integrate at least several TCGA data types) unless they are highly novel and/or represent exceptional improvements over current methods);
Methods to analyze a single gene, its transcription, or its non-coding functional element(s) (because analytical approaches should accommodate representation of all genes covered in TCGA data resources);
Basic software development tools and/or computer programming toolkits; and
Minimal improvements on current data analysis visualization methods or technologies.

To encourage the consideration of novel approaches, applicants responding to this FOA are not required to have preliminary data. However, the research project must be scientifically and technically sound. Also alternative solutions must be proposed for high risk steps in the research plan. In the absence of preliminary data, applicants are encouraged to present any other information that may be relevant to the assessment of project feasibility, for example, the track record of the PI s accomplishments in similar endeavors.

Plans for Method/Tool Validation. For any computational approach/method/tool proposed, a description in the application must include specific plans for experimental validation of the approach. These plans must enable a clear (and quantitative if appropriate) demonstration of technological improvements to be developed upon the project completion. Applicants are thus expected to propose developmental benchmarks and timeline to meet these benchmarks (for details, see SectionIV.6. Other Submission Requirements).

For this validation, it will be important to substantiate the ultimate value and role of the new or improved technology in the analysis of genomic level datasets linked to pathological/clinical data and how this technology would aid the achievement of the goals of TCGA in the future. Applicants should outline how the new technology will be superior compared to existing tools and methods. Applicants should also discuss both the ultimate potential applicability of the technology. The inclusion of sound plans for experimental validation will significantly strengthen merit of the application.

Dissemination of new technology/improvements. An important feature of any newly developed method or tool is the ease with which it can be disseminated and utilized by other laboratories and investigators. Therefore, the issues of access to the invention(s), documentation, and/or technology transfer, should be described in the Research Plan section of the application. These aspects should be addressed in Data and Resource Sharing Plans (see Section IV.6. Other Submission Requirements).

Collaboration with Other Organizations. Collaborations between private sector (for-profit) organizations and not-for-profit/academic institutions may facilitate various projects pertinent to the goals of this FOA. Although a for-profit organization is not a required component, the NCI encourages applicants responding to this FOA to consider such collaborations. Investigators from both not-for-profit and for-profit institutions/organizations can submit applications as the Principal Investigators (PIs). Alternatively, sub-contract relationships with other institutions submitting applications are also possible. Please see Section IV.2. Content and Form of Application Submission for additional information,

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 Announcement (FOA) will use the NIH Exploratory Research Grant (R21) award mechanism. The applicant will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses Just-in-Time information concepts. It also uses the modular as well as the non-modualar budget formats (see the Modular Applications and Awards section of the NIH Grants Policy Statement. Specifically, if you are submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs), use the PHS398 Modular Budget component provided in the SF424 (R&R) Application Package and SF424 (R&R) Application Guide (see specifically Section 5.4, Modular Budget Component, of the Application Guide).

All Domestic applicants must complete and submit modular budgets.

All foreign applicants must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA. See NOT-OD-06-096, August 23, 2006.

Exploratory/developmental grant support is for new projects only; competing renewal (formerly competing continuation ) applications will not be accepted.

2. Funds Available

The total project period for an application submitted in response to this FOA may not exceed 2 years. Although the size of award may vary with the scope of research proposed, it is expected that applications will stay within the budgetary guidelines for an exploratory project. Direct costs are limited to $275,000 over a 2-year period, with no more than $200,000 in direct costs allowed in any single year. Applicants may request direct costs in $25,000 modules, up to the total direct costs limitation of $275,000 for the combined 2-year award period.

The National Cancer Institute intends to commit approximately $2,000,000 in FY2008 to fund six to ten applications.

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 submission of a sufficient number of meritorious applications.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004, November 2, 2004.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit an application(s) if your institution/organization has any of the following characteristics:

Public/State Controlled Institution of Higher Education;
Private Institution of Higher Education;
Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education);
Nonprofit without 501(c)(3) IRS Status (Other than Institution of Higher Education);
Small Business;
For-Profit Organization (Other than Small Business);
State Government;
U.S. Territory or Possession;
Non-domestic (non-U.S.) Entity (Foreign Organization);
Eligible agencies of the Federal government.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a team science approach that clearly does not fit the single-PD/PI model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a single PD/PI or multiple PD/PI grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for multiple PD/PI grants will require additional information, as outlined in the instructions below. The NIH review criteria for approach, investigators, and environment have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PD/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

This program does not require cost sharing as defined in the current NIH Grants Policy Statement.

3. Other-Special Eligibility Criteria

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

Section IV. Application and Submission Information

To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

Grants.gov (http://www.grants.gov/GetStarted); and
eRA Commons (http://era.nih.gov/ElectronicReceipt/preparing.htm).

PDs/PIs should work with their institutions/organizations to make sure they are registered in the eRA Commons.

Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows:

1) Organizational/Institutional Registration in Grants.gov/Get Started

Your organization will need to obtain a Data Universal Number System (DUNS) number and register with the Central Contractor Registration (CCR) as part of the Grants.gov registration process.
If your organization does not have a Taxpayer Identification Number (TIN) or Employer Identification Number (EIN), allow for extra time. A valid TIN or EIN is necessary for CCR registration.
The CCR also validates the EIN against Internal Revenue Service records, a step that will take an additional 1 to 2 business days.
Direct questions regarding Grants.gov registration to:
Grants.gov Customer Support
Contact Center Phone: 800-518-4726
Business Hours: M-F 7:00 a.m. - 9:00 p.m. Eastern Time
Email: support@grants.gov

2) Organizational/Institutional Registration in the eRA Commons

To find out if an organization is already Commons-registered, see the "List of Grantee Organizations Registered in NIH eRA Commons.
Direct questions regarding the Commons registration to:
eRA Commons Help Desk
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Business hours: M-F 7:00 a.m. 8:00 p.m. Eastern Time
Email: commons@od.nih.gov

3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

The individual(s) designated as PDs/PIs on the application must also be registered in the NIH eRA Commons. In the case of multiple PDs/PIs, all PDs/PIs must be registered and be assigned the PI role in the eRA Commons prior to the submission of the application.
Each PD/PI must hold a PD/PI account in the Commons. Applicants should not share a Commons account for both an Authorized Organization Representative/Signing Official (AOR/SO) role and a PD/PI role; however, if they have both a PD/PI role and an Internet Assisted Review (IAR) role, both roles should exist under one Commons account.
When multiple PDs/PIs are proposed, all PDs/PIs at the applicant organization must be affiliated with that organization. PDs/PIs located at another institution need not be affiliated with the applicant organization, but must be affiliated with their own organization to be able to access the Commons.
This registration/affiliation must be done by the AOR/SO or their designee who is already registered in the Commons.

Both the PD/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.

Several of the steps of the registration process could take 4 weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.

For further assistance, contact GrantsInfo -- Telephone: 301-710-0267; Email: GrantsInfo@nih.gov.

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

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide for this FOA through Grants.gov/APPLY.

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH (e.g., the Credential log-in field of the Research & Related Senior/Key Person Profile component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

The SF424 (R&R) application is comprised of data arranged in separate components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY will include all applicable components, required and optional. A completed application in response to this FOA will include the following components:

Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget (Domestic applicants) or Research & Related Budget (Foreign applicants), as appropriate (See Section IV.6., Special Instructions, regarding
ppropriate required budget component.)
Research & Related Budget (required for foreign applications)

Optional Components:
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form

Foreign Organizations (Non-Domestic [non-U.S.] Entity)

NIH policies concerning grants to Foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.

Applications from Foreign organizations must:

Request budgets in U.S. dollars.
Prepare detailed budgets for all applications (that is, complete the Research & Related Budget component of the SF424 (R&R) application forms not the PHS398 Modular Budget component). See NOT-OD-06-096, August 23, 2006.
Charge back of customs and import fees is not allowed.
U.S. Government grants cannot pay taxes in foreign countries, including VAT tax.
Format: Every effort should be made to comply with the format specifications, which are based upon a standard U.S. paper size of 8.5 x 11 within each PDF.
Funds for up to 8% administrative costs (excluding equipment) may be requested. See NOT-OD-01-028, March 29, 2001.
Organizations must comply with Federal/NIH policies on human subjects, animals, and biohazards.
Organizations must comply with Federal/NIH biosafety and biosecurity regulations. See Section VI.2., Administrative and National Policy Requirements.

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the "Contact PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered in Item 15 of the SF424(R&R) Cover component. All other PDs/PIs should be listed in the Research & Related Senior/Key Person component and assigned the project role of PD/PI. Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the Credential field of the Research & Related Senior/Key Person component. Failure to include this data field will cause the application to be rejected.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership of the project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled Multiple PD/PI Leadership Plan (Section 14 of the Research Plan Component in the SF424 (R&R)), must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, including communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

Applications Involving a Single Institution

When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide.

Applications Involving Multiple Institutions

When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution.

When submitting a modular budget, the prime institution completes the PHS398 Modular Budget component only. Information concerning the consortium/subcontract budget is provided in the budget justification. Separate budgets for each consortium/subcontract grantee are not required when using the Modular budget format. See Section 5.4 of the Application Guide for further instruction regarding the use of the PHS398 Modular Budget component.

3. Submission Dates and Times

See Section IV.3.A for details.

3.A. Submission, Review, and Anticipated Start Dates
Opening Date: November 10, 2007 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date: November 10, 2007
Application Submission/Receipt Date: December 10, 2007
Peer Review Date(s): February/March 2008
Council Review Date: May 2008
Earliest Anticipated Start Date: July 2008

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

Descriptive title of proposed research;
Name, address, and telephone number of the PD/PI;
Names of other key personnel;
Participating institutions; and
Number and title of this funding opportunity.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Daniela S. Gerhard, Ph.D.
Director
Office of Cancer Genomics
National Cancer Institute
Building 31, Room 10A07, MSC 2580
31 Center Drive
Bethesda, MD 20892-2580
Telephone: (301) 451-8027
FAX: (301) 480-4368
Email: gerhardd@mail.nih.gov

3.B. Submitting an Application Electronically to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/Apply and follow Steps 1-4. Note: Applications must only be submitted electronically. PAPER APPLICATIONS WILL NOT BE ACCEPTED.

3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application submission/receipt date(s). (See Section IV.3.A. for all dates.) f an application is not submitted by the receipt date(s) and time, the application may be delayed in the review process or not reviewed.

Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have 2 business days to view the application image.

If everything is acceptable, no further action is necessary. The application will automatically move forward for processing by the Division of Receipt and Referral, Center for Scientific Review, NIH, after 2 business days.
Prior to the submission deadline, the AOR/SO can Reject the assembled application and submit a changed/corrected application within the two-day viewing window. This option should be used if the AOR/SO determines that warnings should be addressed. Reminder: warnings do not stop further application processing. If an application submission results in warnings (but no errors) it will automatically move forward after two business days if no action is taken. Please remember that some warnings may not be applicable or may need to be addressed after application submission.
If the two-day window falls after the submission deadline, the AOR/SO will have the option to Reject the application if, due to an eRA Commons or Grants.gov system issue, the application does not correctly reflect the submitted application package (e.g., some part of the application was lost or didn t transfer correctly during the submission process). The AOR/SO should first contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine the best course of action. NIH will not penalize the applicant for an eRA Commons or Grants.gov system issue.
If the AOR/SO chooses to Reject the image after the submission deadline for a reason other than an eRA Commons or Grants.gov system failure, a changed/corrected application still can be submitted, but it will be subject to the NIH late policy guidelines and may not be accepted. The reason for this delay should be explained in the cover letter attachment.
Both the AOR/SO and PD/PI will receive e-mail notifications when the application is rejected or the application automatically moves forward in the process after 2 days.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH and responsiveness by the NCI. Incomplete applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons . Information related to the assignment of an application to a Scientific Review Group is also in the Commons.

Note: Since email can be unreliable, it is the responsibility of the applicant to check periodically on their application status in the Commons.

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.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new award.

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

6. Other Submission Requirements

PD/PI Credential (e.g., Agency Login)

The NIH requires the PD/PI to fill in his/her Commons User ID in the PROFILE Project Director/Principal Investigator section, Credential log-in field of the Research & Related Senior/Key Person Profile component. The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Registration FAQs Important Tips -- Electronic Submission of Grant Applications.

Organizational DUNS

The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Warning: Please be sure that you observe the direct cost, project period, and page number limitations specified above for this FOA. Application processing may be delayed or the application may be rejected if it does not comply with these requirements.

PHS398 Research Plan Component Sections

While each section of the Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.

All application instructions outlined in the SF424 (R&R) Application Guide (MS Word or PDF) are to be followed, incorporating "Just-in-Time" information concepts, and with the following requirements for R21 applications:

R21 applications will use the modular as well as the non-modular budget formats and "Just-in-Time" information concepts, with direct costs requested in $25,000 modules, up to the total direct costs limitation of $275,000 over an R21 2-year period. No more than $200,000 in direct costs will be allowed in any single year. All Domestic applicants must use modular budgets. All foreign applicants must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA. See NOT-OD-06-096, August 23, 2006.
Items 2-5 of the Research Plan component of the R21 application may not exceed 15 pages, including tables, graphs, figures, diagrams, and charts.
Preliminary data are not required but may be included (within the page limit) if available.
Renewal (formerly competing continuation or Type 2 ) applications are not permitted.

Timeline to Meet Developmental Guidelines

Research Plan should include a dedicated subsection describing the proposed developmental benchmarks and timeline to meet these benchmarks. Examples of elements and timing that may be discussed in this section include:

Completion of a designing/planning stage to take advantage of caBIG tools and resources and specific TCGA datasets;
Demonstration of partial functionality (generation of an alpha version) of the analytical tool, software, and/or visualization technology (as applicable to a specific project);
Developing and testing of a beta version of the analysis tool, software, or visualization technology that uses actual TCGA data and takes advantage of caBIG infrastructure;
Developing a final, fully functional version of the analytical tool, software, and/or visualization technology;
Validation of final version of the analysis tool, software, and/or visualization technology by comparing it to existing functionalities.
Criteria of successful validation (specific metrics that will be used to demonstrate superiority of the new software or visualization technology over the existing tools); and
Transferring the validated analytical tool, software, and/or visualization technology to appropriate recipients (indicated by OCG) for its public implementation in caBIG infrastructure.

These examples are neither meant to be comprehensive nor uniformly applicable. Applicants are encouraged to propose specific benchmarks and timelines that are deemed most appropriate for their specific projects.

Appendix Materials

NIH has published new limitations on grant application appendix materials to encourage applications to be as concise as possible while containing the information needed for expert scientific review. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-018.html.

Applicants must follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide (see http://grants.nih.gov/grants/funding/424/index.htm).

R21 Appendix materials should be limited, as is consistent with the exploratory nature of the R21 mechanism.

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.

Foreign Applications (Non-Domestic [non-U.S.] Entity)

Indicate how the proposed project has specific relevance to the mission and objectives of the NCI and has the potential for significantly advancing the health sciences in the United States.

Guidelines for Sharing Research Data and Resources. Since TCGA is a scientific community resource project, all data and resources including, methods, tools, software and technologies resulting from this project are expected to be made available for public dissemination. Therefore, all applications proposed in response to this FOA must include Data Sharing Plan and Resource Sharing plan (or explaining why such sharing is not possible). Both plans should be entered under the Resource Sharing Plan component in the SF424 package.

The precise content of these plans will vary depending on the technology, tool and/or method being developed, the data being collected and how the investigator is planning to share the data/resource(s). In this section, applicants may wish to describe briefly the expected schedule for resource sharing, the documentation to be provided, and whether or not a sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can use the resource(s) and whether or not any conditions will be placed on their use), and the mode of 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 technology and/or data-sharing agreement. References to resource sharing may also be appropriate in other sections of the application.

The general, NIH-wide policies and requirements for data and resource sharing plans are summarized below.

Plan for Sharing Research Data

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.

More information on the NIH data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing.

Sharing Research Resources

NIH policy expects that grant 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 http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). 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.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590). See Section VI.3., Reporting.

Section V. Application Review Information

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 National Cancer Institute in accordance with the review criteria stated below.

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

Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score;
Receive a written critique; and
Receive a second level of review by the National Cancer Advisory Board.

Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications. The following will be considered in making funding decisions:

Scientific merit of the proposed project as determined by peer review;
Availability of funds; and
Relevance to program priorities.

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application.

Significance
Approach
Innovation
Investigator
Environment

Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, and/or preventative interventions that drive this field?

Specific to this RFA: Does the applicant describe how the technology developed is an improvement over current tools and technologies? Will these improvements have significant impact on the analyses of the TCGA datasets?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? For applications designating multiple PDs/PIs, does the Leadership Plan ensure that there will be sufficient coordination and communication among the PDs/PIs? Are the administrative plans for the management of the research project appropriate, including plans for resolving conflicts?

Specific to this RFA: Does the technology adequately integrate the different technology platforms, caBIG standards and data types available within the TCGA database? Is there adequate validation plan proposed? How appropriate and realistic are the proposed benchmarks and timelines? How well will the proposed efforts take advantage of caBIG systems and adhere to caBIG standards?

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, and/or technologies for this area?

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

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

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 Human Subjects Sections of the PHS398 Research Plan component of the SF424 (R&R).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated. See the Human Subjects Sections of the PHS398 Research Plan component of the SF424 (R&R)

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the adequacy of the plans for their care and use will be assessed. See the Other Research Plan Sections of the PHS398 Research Plan component of the SF424 (R&R).

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget and Period of Support: The reasonableness of the proposed budget and the appropriateness of the requested period of support in relation to the proposed research may be assessed by the reviewers. The priority score should not be affected by the evaluation of the budget.

Applications from Foreign Organizations: Whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, and/or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources will be assessed.

2.C. Sharing Research Data

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 funding organization will be responsible for monitoring the data sharing policy (http://grants.nih.gov/grants/policy/data_sharing).

2.D. Sharing Research Resources

NIH policy expects that grant 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 http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). 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 and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590), See Section VI.3., Reporting.

3. Anticipated Announcement and Award Dates

Not applicable.

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his/her Summary Statement (written critique) via the NIH eRA Commons.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Section IV.5., Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

Section VII. Agency Contacts

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

1. Scientific/Research Contacts:

Daniela S. Gerhard, Ph.D.
Director
Office of Cancer Genomics
Office of the Director
National Cancer Institute
Building 31, Room 10A07, MSC 2580
31 Center Drive
Bethesda, MD 20892-2580
Telephone: (301) 451-8027
FAX: (301) 480-4368
Email: gerhardd@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 mail)
Rockville, MD 20852 (for non-USPS express/courier delivery)
Telephone: (301) 496-3428
FAX: (301) 402-0275
Email: ncirefof@dea.nci.nih.gov

3. Financial or Grants Management Contacts:

Emily Linde
Office of Grants Administration
National Cancer Institute
3120 Executive Boulevard, EPS Room 243, MSC 7148
Bethesda, MD 20892-7148 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for non-USPS express/courier delivery)
Telephone: (301) 496-8784
Fax: (301) 496-8601
Email: lindee@mail.nih.gov

Section VIII. Other Information

Required Federal Citations

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

Human Subjects Protection:
Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (Phase I); efficacy studies (Phase II); and efficacy, effectiveness, and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants ( NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

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. Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the SF424 (R&R) application; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research. Applications that do not provide this information will be returned without review.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from: 1) currently funded NIH research projects; or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

For more information about the Policy or the submission process, please visit the NIH Public Access Policy Web site at http://publicaccess.nih.gov/ and view the Policy or other Resources and Tools, including the Authors' Manual.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (HHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the HHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission identification numbers must be used for publicly accessible on-line journal articles. Publicly accessible on-line journal articles or PMC articles/manuscripts accepted for publication that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference in either the Bibliography & References Cited section, the Progress Report Publication List section, or the Biographical Sketch section of the NIH grant application. A URL or PMC submission identification number citation may be repeated in each of these sections as appropriate. There is no limit to the number of URLs or PMC submission identification numbers that can be cited.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for 2 years to the research. For further information, please see: http://www.lrp.nih.gov.