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.cancer.gov/

Title: Genome Characterization Centers and Genome Data Analysis Centers for The Cancer Genome Atlas Research Network (TCGA)[U24]

Announcement Type
New

Update: The following update relating to this announcement has been

Request For Applications (FOA) Number: RFA-CA-09-010

Catalog of Federal Domestic Assistance Number(s)
93.393, 93.394, 93.395, 93.396, 93.397, 93.399, 93.398

Key Dates
Release Date: January 7, 2009
Letters of Intent Receipt Date: February 13, 2009
Application Receipt Date: March 13, 2009
Peer Review Date(s): June-July 2009
Council Review Date: August 2009
Earliest Anticipated Start Date: September 2009
Additional Information To Be Available Date (Url Activation Date): Not Applicable
Expiration Date: March 14, 2009

The NCI will hold a pre-application meeting several weeks before the application submission deadline to which all interested prospective applicants are invited (either in person or via videocast). NCI program and review staff members will make presentations to explain the goals and objectives for The Cancer Genome Atlas Research Network, to discuss the application peer review process, and to answer questions.  An NCI Grants Management Specialist will be available to answer financial questions.  A Notice with the details of the meeting will be issued in the NIH Guide for Grants and Contracts (go to http://grants.nih.gov/grants/guide/index.html).

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Purpose. This funding opportunity announcement (FOA) is designed to support The Cancer Genome Atlas (TCGA) research network. The overall goal of this phase of the TCGA initiative is to provide genome-wide catalogs of genomic alterations in 20-25 different types of human cancer that could be used to identify and accelerate the development of new diagnostic and prognostic markers, new targets for pharmaceutical interventions, and new cancer prevention and treatment strategies.  Under this FOA, the NCI solicits applications for two types of centers. (1) Genome Characterization Centers (GCCs); and (2) Genome Data Analysis Centers (GDACs, that must be oriented on one of two permissible types of analytical pipelines). An applicant/institution may submit one application for either type of centers or two applications for two different types (with certain restrictions regarding subtypes of GDACs). GCCs will utilize novel high-throughput, high resolution technologies to comprehensively (i.e., genome-wide) detect genomic, epigenomic and transcriptome aberrations including: alterations in chromosome segment copy numbers, translocations, loss of heterozygosity, altered DNA methylation patterns and changes in gene expression, which may play a role in cancer. GDACs will focus on the integration and analysis of data generated by the GCCs and other TCGA components, development of innovative bioinformatic and computational tools and the performance of advanced bioinformatic analyses including, but not limited to: systems biology approaches to discovery, pathway analysis models, and integrative data analysis methods with accompanying visualization tools to identify complex genomic changes; and integrated cancer biology and translational discovery models that will increase our understanding of cancer as a disease process.  Prior contribution to the TCGA Pilot Project is not required and all qualified institutions and individuals are encouraged to apply to this FOA.

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                                                             

Purpose:

This FOA is part of The Cancer Genome Atlas (TCGA) Research Network and is an extension of The Cancer Genome Atlas (TCGA) Pilot Project (http://cancergenome.nih.gov/), co-funded by the NCI and the National Human Genome Research Institute (NHGRI).  The overall purpose of TCGN is to improve our understanding of the genomic alterations associated with the onset and progression of human cancers. This knowledge is expected to lead to novel translational approaches and, ultimately, to accelerate the development of new cancer diagnostic, prevention, and treatment strategies.  It is not the intent of this FOA to fund follow-up translational and functional studies, but rather to enable the cancer research community to develop a new generation of studies that will leverage TCGA findings for the benefit of cancer patients. TCGA data will provide a unique reference resource on cancer-specific genomic aberrations for the cancer research community at large. 

To serve the overarching goals of TCGA, this FOA solicits applications for two types of highly collaborative Centers, both of which will be important components of TCGA:

1.     Genome Characterization Centers (GCCs) and

2.     Genome Data Analysis Centers (GDACs, two sub-types).

An additional component of TCGA, a Data Coordinating Center (DCC), will serve as the hub and central repository of characterization data from the GCCs as well as processed and integrated data from GDACs.

Main Goals for GCCs.  It is expected that an interactive group of multidisciplinary Genome Characterization Centers (2-4) will be funded under this FOA. The GCCs will use various genomic and/or epigenomic analysis technologies for the high-resolution, systematic, comprehensive (genome-wide) characterization of cancer-related genomic alterations. The GCCs will apply appropriate optimized and standardized high-throughput technologies to the analyses of defined sets of cancer biospecimens (to be provided by the Biospecimen Core Resource of TCGA).  GCCs will generate data at four levels (defined at http://tcga-data.nci.nih.gov/docs/TCGA_Data_Primer.pdf), which include: (a) raw, “level 1” data; (b) processed “level 2” data; (c) segmented “level 3” data; and (d) summary of all cases “level 4” data. GCCs will submit their data at levels 1-4 to DCC.

Main Goals for GDACs.  It is expected that 2-6 multi-disciplinary, interactive GDACs will be established under this FOA. GDACs will develop two types of analytical pipelines. The first goal is to develop and implement appropriate bioinformatic systems using already developed and available analytical tools, quality control measures, and bioinformatic tools for rapid high-throughput processing and analyses of genome-wide data through an analytical pipeline (Type A).  The second goal will be to create a “biology-centric computational” pipeline (Type B) for more advanced analyses designed to provide analysis models and identify potential translational directions and outcomes from TCGA data. The first Type A pipeline is designed to integrate TCGA data via a high-throughput automated pipeline. The second, biology-driven computational Type B pipeline will utilize advanced and novel algorithms, models and other bioinformatics and computational tools to provide biologically relevant results from TCGA standardized molecular data and integrate clinical data. These systems and tools and established analytical pipelines will be used to process analytical data from other data types from the TCGA (primarily GCCs and Genome Sequencing Centers [GSCs, see description below]) deposited in the DCC to generate integrated results that would enable the clinical and translational application of TCGA data.

Reflecting these two types of analytical pipelines, there will be two types of GDACs. Type A GDAC(s) will perform data integration and Type B GDAC(s) will conduct higher levels of translational genomic analysis. All GDACs will work together to: develop a strategy for data flows through the various groups via the DCC; determine the various types of analyses to be performed; and optimize the mechanism(s) for communicating back to the participants in the project as well as the scientific community. GDACs will also be responsible for submitting their results on the identified cancer-associated molecular alterations to the DCC.

This FOA is open to all qualified individuals and institutions and does not require prior participation in the TCGA Pilot Project.

Note 1: In this document, the term “characterization” of cancer-related genomic alterations refers to the generation of molecular data from biospecimens (by the GCCs), whereas “analysis” refers to the bioinformatic analysis and integration of data via bioinformatics approaches and computational tools..

Background

Cancer is a complex and heterogeneous disease in which mutations and other genomic and epigenomic abnormalities play a role in both its initiation and progression.  Accumulated research data implicate numerous somatic mutations and a more limited number of inherited mutations in carcinogenesis.  Understanding cancer-specific somatic mutations can provide important clues regarding the molecular processes underlying the development and progression of certain tumors.  Given cancer’s complexity, it is generally believed that only a fraction of alterations that may be useful as characteristic markers of specific tumor types and/or potential molecular targets have been identified to date.  Therefore, to be successful, comprehensive genomic analyses of cancer must overcome a broad range of challenges stemming from the biological complexity and heterogeneity of human tumors and subtypes.  An important role in tumor heterogeneity is played by the genomic instability, which is inherent to the progression of cancer.  The dynamic changes in tumor genomes are influenced by the cellular and biological context, genetic characteristics of individual persons, and environmental factors.  Certain similarities exist across tumor types, however any effort to characterize the genomes of tumors in a comprehensive, systematic manner must address the heterogeneity across distinct cancer types and subtypes.

Many research groups are working independently to identify cancer-relevant genomic changes (e.g., alterations in expression profiles, chromosome deletions, amplifications, and/or translocations) in a relatively small number of samples.  Cancer-relevant changes have been detected at diverse levels of genomic organization; they include point mutations, chromosomal deletions, amplifications, translocations, and/or changes in the number of individual chromosomes, all of which can, in principle, contribute to transcriptional aberrations.  However, in terms of comprehensive cataloging, these individualized, researcher-initiated and uncoordinated approaches are limited. Such studies are inherently fragmentary (e.g., by technology and/or tumor specimens analyzed) and difficult to integrate because of data compatibility issues across studies and tumor types/sub-types. 

The Cancer Genome Atlas (TCGA) Pilot Project.  In 2006, the NCI and the National Human Genome Research Institute initiated a collaboration to pursue a 3-year pilot project to determine the feasibility of cataloging the genomic alterations associated with a small number of different human cancers. The pilot project focused mainly on three tumor types [glioblastoma multiforme (GBM), serous cystadenocarcinoma of the ovary, and squamous carcinoma of the lung]. The goal was to assess the technical feasibility and clinical relevance of conducting a comprehensive analysis of the associated genomic alterations. The pilot project demonstrated that cancer-associated genes and genomic regions can be identified by combining diverse information from genome analyses (as defined in the previous paragraph), with tumor biology and clinical data, and that the sequencing of selected regions can be conducted efficiently and cost-effectively.  Achievement of the pilot project goals has set the stage for the next phase of TCGA that promises to rapidly and efficiently generate analogous genomic data for all major cancer types and subtypes. The comprehensiveness and rate of progress of TCGA will depend on both optimization of technical issues and resource availability. 

During the pilot phase of TCGA the collective genomic and clinical data generated and integrated by all TCGA components, provided the initial contributions to a comprehensive Web-based resource describing the genomic profiles of specific cancer types. This resource is known by the same title as the project - The Cancer Genome Atlas.  Three key “lessons learned” during the TCGA Pilot project were that to be able to interpret the results generated by the various characterization platform the Centers had to utilize high quality molecular analytes; perform experiments utilizing strict standardized protocols; and deposit the results in structured formats.  The last lesson strongly impacted on the ability of the various analytical groups to extract meaningful results from the genomic data generated.  These lessons learned will be applied to this phase of TCGA. 

The Cancer Genome Atlas as a Coordinated Effort. The unique aspect of TCGA Pilot Project was the development and function of an integrated research network. The current phase of TCGA will utilize a similar model. The intent of TCGA is to conduct a coordinated and comprehensive, genome-wide analysis of cancer-relevant alterations by simultaneously applying several technologies to interrogate the genome, epigenome or transcriptome in large collections of quality controlled cancer biospecimens derived from specific cancer types. To accomplish this goal, TCGA includes multidisciplinary teams of investigators and associated institutions that collectively provide biological data, as well as inform strategies for sequencing.  The progress in understanding some cancer-associated molecular alterations and the accompanying advances in technology suggest that it is now possible to obtain comprehensive genomic information from multiple tumor types to catalog most, if not all, of the genomic changes associated with cancer.  Ultimately, in collaboration with and in support of the NCI’s extensive program of individual projects in cancer research, such efforts are expected to accelerate the identification of markers for prevention and diagnosis and novel targets for the development of therapeutic drugs, as well as provide the basis for a refined clinical understanding of patient stratification in therapy.

The TCGA Pilot Project Research Network includes the following major organizational and functional components:

Technology Development:

Overall Research Objectives and Specific Requirements of this FOA

Applicants responding to this FOA may apply for one or two types of centers but must submit a separate application for each specific type of center proposed. See Section II.3. Other-Special Eligibility Criteria of this FOA for permissible combinations.

Specific objectives, requirements, and expectations for both types of centers are given below.

Research Objectives for GCCs:

The overarching goal for the GCCs is the high-resolution, systematic, comprehensive (genome-wide) characterization of cancer-related genomic alterations. These types of characterization should be conducted using validated methods in a high-throughput fashion at the start of the project. The cancer biospecimens for these studies (DNA, RNA, cells [for epigenetic studies of histone modifications] or other types of samples required by a platform) will be provided by the Biospecimen Core Resource of TCGA].  The aim is to have all the characterizations conducted on biomolecules from the same biospecimens for optimal analytical integration for data comparability.  The GCCs are expected to generate these genomic data by using optimized and standardized high-throughput technologies. Based on this premise, tumor sample eligibility for TCGA will be based on the analyte quantity and quality requirements of the technologies, which will be centrally verified by the BCR, but may include any histopathological type of tumor.  Specific goals for GCCs (outlined below) will require interdisciplinary cooperation among cancer molecular biologists, clinical researchers, genomic technology specialists, and bioinformaticians.

GCC Objective 1: Use one or more high-throughput, cost-effective genome characterization technologies to characterize comprehensively (i.e., genome-wide) genomic or epigenomic or transcriptome alterations of any type known to be generally relevant to human cancer.

An appropriate technology may be, for example, an improved version selected from technologies evaluated in the TCGA Pilot Project (http://cancergenome.nih.gov/components/cgcc.asp), those developed through TCGA Pilot Project technology development awards (http://cancergenome.nih.gov/media/news_7_2_2007.asp) or other validated methods that are capable of giving high quality data when used in a high-throughput setting as demonstrated by sufficient data to statistically validate the capabilities of the proposed platform. A technology/method is considered pre-validated if it satisfies at least one of the following: (1) the results of genomic feature detection using the chosen platform have been corroborated (at a statistically significant rate) by at least one alternative technology as evidenced by previously published comparative analyses; (2) for the chosen technology platform, a validated method has been previously established (and can be readily implemented) for accepting or rejecting a data set based on concomitant analyses of appropriate, known positive and/or negative control samples. Other technologies may be eligible as identified in Research Plan below. Desirable characterizations include: the detection of changes in DNA segment copy numbers; aberrant gene expression profiles; detection and defining exact location of translocations and breakpoints; mutation detection; and/or DNA methylation patterns.  Other technologies may be eligible as identified in Research Plan below.

Requirements for GCC Objective 1:

GCC Objective 2: Improve performance of the large-scale genomic characterization technology platform used in Objective 1. Applicants may propose specific efforts to improve the selected technology platform and/or switch to more advanced platforms as demonstrated appropriate, i.e. the platform is properly validated (as defined above).  In general, improvements/optimization efforts sought include (but are not limited to): (a) enhancing detection sensitivity and/or resolution; (b) increasing throughput; (c) optimizing genome coverage; and (d) reducing unit costs per analysis.

Requirements for GCC Objective 2:

GCC Objective 3: Implementation of quality assurance criteria for platform(s) used in Objectives 1 and 2 and use of these criteria to select data that are of sufficiently high quality to be submitted to the TCGA database.

Requirements for GCC Objective 3:

Research Objectives for GDACs:

This FOA is intended to fund an integrated group of GDACs with each GDAC developing either of the two types of analytical pipelines and performing the integrative analyses outlined in the FOA.  The members of the GDAC group will (1) implement one of two bioinformatic pipelines using existing state-of-the-art tools for timely high-throughput processing and integrated analyses of genome-wide data (Type A and Type B GDACs); (2) develop and implement new bioinformatics and computational tools to capture key biological parameters such as pathway analysis, data integration with visualization, and integrated cancer biology (Type B GDACs); (3) develop pipeline and network-wide quality control methods for the system in (1) and (2) above; and (4) process/integrate analytical data from other components of TCGA to generate disease level findings and interpretations (Type A and B GDACs).  These ambitious goals will necessitate continuous communication and interactions among the members of TCGA network.  Each member of the GDAC group will have distinct functions and capabilities and be responsible for individual analytical components. For example, Type A GDACs would be responsible for developing an integrative analytical pipeline, while Type B GDACs would be responsible for developing an advanced, translational genomics analysis pipeline.  The expectation is that that there may be 1-4 Type A GDACs and 1-4 Type B GDACs (the cumulative number of both GDAC types is expected to be 2-6).  The applications should include suggestions on how the future GDAC awardees would interact as the GDAC working group (GDACWG).

Each GDAC applicant team must have current expertise in computational data analysis and genomics-specific bioinformatics as well as clinical oncology and/or cancer biology.  GDACs would benefit greatly by being jointly led by two investigators: (i) an expert in bioinformatics/computation and (ii) either a clinical oncologist or a cancer biologist who can help to guide the analyses and contribute to the interpretation of the results at the disease-level.  GDACs are expected to be led by two individuals representing the fields mentioned above.

The Type A and Type B GDACs differ by the proportion of the effort devoted to the development of novel analyses, but each GDAC will be required to develop  novel approaches to data analysis and data integration.  The GDACs will generate two analytical pipelines, each of which will be available as a resource to the scientific community for data integration and for advanced translational evaluation of TCGA data.  The analytical pipelines may result in valid conclusions which are not 100% concordant due to the different analytical method used.  The GDACs will need to develop annotation which will be made available along with the pipeline on the DCC to explain any differences in data interpretation to the research community.

GDAC Objective 1: Implement an integrative bioinformatics approach utilizing existing bioinformatic tools for timely high-throughput processing and analyses of genome-wide data (requires a design document). This objective applies to Type A GDACs.

Requirements for GDAC Objective 1:

GDAC Objective 2: Development of innovative bioinformatics and computational tool development (requires drawing clinical and biological correlations) (a design document is expected).  This objective applies only to Type B GDACs..

Requirements for GDAC Objective 2:

GDAC Objective 3: Conduct Integrative analysis of data sets generated by GCCs and other TCGA components using the bioinformatic pipeline developed either under Objective 1 or 2.

Requirements for Objective 3:

caBIG Compatibility (GCCs and GDACs). 

For both GCCs and GDACs, all the proposed data types and outputs must comply with data standards of cancer Biomedical Informatics Grid (caBIG, https://cabig.nci.nih.gov/) as a unified platform for sharing and disseminating information. 

Data Sharing Requirements for GCCs and GDACs. Public availability of data/information generated by TCGA will be critical to facilitate disease-relevant discoveries of clinical significance. Therefore, sharing as a public resource all rigorously validated data is essential for this initiative. For the entire TCGA, the role of central data repository will be served by the Data Coordinating Center (DCC, http://cancergenome.nih.gov/components/dmbca.asp).  The content of DCC will be continuously updated by GCCs, GSCs and GDACs. Therefore, all GCC and GDAC applicants are required to submit a Data Sharing Plan documenting how and when data will be released and shared.  The Data Sharing Plan must be consistent with the goals of TCGA described in this FOA, with NIH data sharing guidelines and the data sharing procedures developed by TCGA Pilot Project (http://www.genome.gov/Pages/Research/DER/TCGA/TCGABrochure.pdf).

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 U24 cooperative agreement funding mechanism.
The Project Director/Principal Investigator(s) [PD(s)/PI(s)] 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". 

2. Funds Available

The NCI intends to commit up to $18 million in total costs in FY 2009, and up to $90 million over the planned 5-year project period, to support 2-4 GCC awards and 2-6 GDAC awards as a result of this FOA. Future year amounts will depend on annual appropriations. 

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size 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 costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

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

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

Additional requirement: Foreign institutions are eligible to apply only if they are located in Canada. Foreign institutions from other countries may participate only under subcontracts to domestic applicant institutions.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD(s)/PI(s) is/are invited to work with his/her/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.

Both GCC applicants and GDAC applicants are strongly encouraged to take advantage of the multiple PDs/PIs option.  For example, the proposed GDACs may include one PD/PI with primary expertise in bioinformatics and another PD/PI with primary experience in cancer biology or clinical oncology.  , the leadership structure should be defined and justified (in the Leadership Plan and other relevant sections). For GCC applicants, it is expected that one of the PD/PIs is identified as an overall “lead” PI. For GDAC applicants, two lead PIs representing complementary fields are encouraged. Given the large-scale of the projects funded under this FOA, lead PD(s)/PI(s) will be expected to devote at least 20% effort to the project. 

Separately, one PD/PI has to be designated as a contact PI (see details below). For additional clarifications regarding the multiple PI option, please visit respective Frequently Asked Questions web page (http://grants.nih.gov/grants/multi_pi/faq.htm#b6.) 

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

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

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

Number of Applications.  Applicants responding to this FOA may apply for one or two types of centers but (a) each applicant may submit only one application for a specific center type and (b) applicants must submit a separate application for each specific type/sub-type of center proposed (i.e., in aggregate, up to two applications are allowed).

The following applications are permissible from an eligible applicant institution:

  1. One application for GCC; or
  2. One application for GDAC (either Type A or B); or
  3. One application for GCC and another (separate) application for GDAC Type A; or
  4. One application for GDAC Type A and another (separate) application for GDAC Type B.

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

Renewals. Only new applications are permitted in response to this FOA.

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 Grants Info, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

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

2. Content and Form of Application Submission

Applicants responding to this FOA may submit the following types of applications:

1    One application for GCC; or

2    One application for GDAC (either Type A or B); or

3    One application for GCC and another (separate) application for GDAC Type A; or

4    One application for GDAC Type A and another (separate) application for GDAC Type B.

Applications must be prepared using the most current PHS 398 research grant application instructions and forms PHS 398 grant application instructions modified as outlined 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. The applicant must indicate in parenthesis to follow the FOA Title in Box 2, whether the application is intended as a (GCC) or (GDAC).

All U24 applicants responding to this FOA must demonstrate in the application their ability and willingness to meet:

MODIFICATIONS OF PHS 398 INSTRUCTIONS

Table of Content (PHS 398 Form Page 3): Modify the standard PHS 398 Table of Contents to account for the modified sections of the Research Plan (see below).

Budget (PHS 398 Form Pages 4 and 5): Follow the current PHS 398 instructions to provide a detailed budget (direct costs) for the entire application for the first 12-month period (Form page 4) and the entire proposed project period (Form page 5).

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:

Note: Numbers of pages suggested below for individual sections are provided solely as a nonbinding guidance for applicants. Applicants are encouraged to use the minimum number of pages necessary to describe the research plan clearly and succinctly.

Other items of the PHS398 Research Plan remain unmodified.

Block A. Organization of Research Plan for GCC Applications

Section N1. Scope of Research;

Section N2. Analytic Capacity of the Instrumental Resources and the Quality Control Procedures;

Section N3. Technology Improvements, Quality Assurance and Quality Control Sharing Research Data, Resources and Intellectual Property; and

Section N4. Applicant Group.

Section N5. Collaboration with Other Organizations;

These sections must cover the following elements:

Section N1: Scope of Research.

The applicants must describe in detail experimental and developmental activities addressing the Specific Research Objectives for GCCs outlined in Section I.1 Research Objectives of this FOA. Reviewers will evaluate how well the applicants have addressed all the general and objective-specific requirements and obligations. Section N1 needs to contain the following elements:

Section N2. Analytic Capability of the Instrumental Resources and the Quality Control Procedures.

Section N3: Technology Improvements, Quality Assurance and Quality Control Sharing Research Data, Resources and Intellectual Property. 

Section N4: Applicant Group and Environment

In this section, applicants should outline the leadership structure and describe in detail the roles of the key personnel. Details and justification of the proposed leadership structure should be provided in a separate section “Leadership Plan” (item 15 in the standard PHS398 instructions). GDAC applicants using the multiple PD/PIs option are encouraged to identify one investigator as an overall “lead” PI (independent of designating a “contact” PI, who may be the same or another person).  For additional clarifications regarding the multiple PI option, please visit respective Frequently Asked Questions web page (http://grants.nih.gov/grants/multi_pi/faq.htm#b6.)

The applicants are expected to summarize their expertise relevant to the scientific and technical scope of the proposed GCC and specific objectives of their applications, including any pertinent ongoing research.  Emphasize, where applicable, the experience and track record of the group in high-throughput data generation projects and in collaborative programs and activities. The PD(s)/PI(s) of a large-scale project funded under this FOA is/are expected to devote at least 20% effort to the project.  Management and governance plans for the group and the PD(s)/PI(s) relevant experience in this regard should be discussed. The content of Section N4 should avoid redundancy with information that is contained in a Multiple PD/PI Leadership Plan (Section 14).  

Describe unique resources, supportive infrastructure and instrumentation available to the project.

The following expertise components and organizational elements must be addressed:

Section N5: Collaboration with Other Organizations.

Block B. Organization of Research Plan for GDAC Applications

Note:  Applications for Type A GDACs will include sections N1, N2, N4 and N5, whereas applications for Type B GDACs will include sections N1, N3, N4 and N5 as indicated below.

Section N1. Standardization of Input and Output Data Types and Integration of Data Sets;

Section N2. Integrative Analysis of Data Sets (Type A GDACs);

Section N3. Translational Genomics Analysis (Type B GDACs);

Section N4. Plan for Sharing Research Data, Resources, and Intellectual Property; and Collaboration with Other Organizations;

Section N5. Applicant Group.

Section N1. Standardization of input and output data types and integration of data sets;

Data Standardization: Applicants should present detailed plans for the use of existing data formats, generated by the GCCs and GSCs, in the development of standardized data sets required for data integration on the applicant’s integration/bioinformatics platform(s) of choice. These plans must take into account that very large data sets will be generated continuously from the start of the project and will require timely analysis. All proposed solutions must be compliant with the caBIG (see more details below) as a unified platform for data sharing and dissemination.  Data generated by the applicant’s analysis platform must also meet caBIG requirements and be made available to other GDACs who may utilize these data for further development/integration utilizing other bioinformatics tools.  Analytical tools may reconfigure input data into specialized forms required for analysis as long as output data are converted into standard forms. Methods of data standardization should be completed within the first six months of funding in anticipation of starting bioinformatics tool development.

Section N2. Integrative analysis of data sets (Type A GDACs)

·It is expected that the majority of a Type A GDAC’s effort (~80%) will be devoted to analyzing the data, generating an analytical pipeline and making it publicly available, while a minority (~20%) will be used for the improvements of the methods and adjustments to new data types.

Section N3. Novel Translational Genomics Analysis (Type B GDACs)

Section N4: Plan for Sharing Research Data, Resources, and Intellectual Property and Collaboration with Other Organizations  

Section N5: Applicant Group

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:

In addition, for applications from foreign organizations:

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  

Applicants are encouraged to use multi- PD(s)/PI(s) mechanism. Use the Face Page-Continued page to provide Items 3a – 3h for all PD/PIs. NIH requires one PD/PI be designated as the “contact PD/PI” for all communications between the PD/PIs and the agency.  The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PD/PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PD/PI may be changed during the project period.  The contact PD/PI should be listed in block 3 of Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in the header of each application page, use the name of the “Contact PD/PI, et. al.”  The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.

All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles such as SO or IAR will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

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

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a section of the research plan, entitled “Multiple PD/PI Leadership Plan” (section 14), 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, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators. 

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

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: February 13, 2009
Application Receipt Date: March 13, 2009
Peer Review Date(s): June-July 2009
Council Review Date: August 2009
Earliest Anticipated Start Date(s): September 2009

3.A.1. Letter of Intent

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

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

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

The letter of intent should be sent to:

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

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

The incurrence of pre-award costs in anticipation of an award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project (see NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.)

6. Other Submission Requirements and Information

Capital Equipment Requests. In general, capital equipment, defined as equipment whose unit costs exceed $5,000, may NOT be budgeted under this FOA. Well justified exceptions may be allowed in rare circumstances (assessed on a case by case basis) but solely for the purpose of increasing analytical throughput of a technology platform to reach the minimal processing capacity.  That technology platform must be already in place and operational in the applicants’ organization.  To justify any capital equipment request, applicants must provide compelling evidence (e.g., preliminary data) that they have experience in the respective technology and already use identical and/or similar equipment, and that the necessary arrangements are in place to have such equipment in operation no later than 3 months from the award and start date of the project period.  If the request is granted, the total capital equipment costs should not exceed $500,000 for the entire project period.

Costs of Participation in TCGA Meetings. Applicants should budget for the PIs and/or alternative designated representatives (in aggregate, up to 5 members of each Center) to attend twice a year meetings held by the TCGA Network Steering Committee, as well as for the principal bioinformatics representative of each GCC, GDAC to attend the caBIG annual meeting.

caBIG compatibility. Both GCC and GDAC applicants must adhere to the formats and standards of the NCI’s Cancer Biomedical Informatics Grid (caBIG, http://cabig.nci.nih.gov). caBIG requires that data be represented as aggregations of Common Data Elements (CDEs) that are registered in the NCI’s Cancer Standards Data Repository (caDSR, http://cadsr.nci.nih.gov). These data elements are, in turn, defined using concepts codes that are maintained in the NCI’s Enterprise Vocabulary System (EVS). Data submitted to the DCC must be unambiguously analyzable into CDEs. In the TCGA Pilot Project, this requirement was met by adopting the MAGE-TAB format (Tim F. Rayner et al. (2006) BMC Bioinformatics, 7, 489), a simple tab-delimited spreadsheet-like format for array-based data, and UCSC’s MAF format (http://genome.ucsc.edu/FAQ/FAQformat#format5) for sequence data. It is expected that these formats will continue to be used, although it may be necessary to define additional CDEs and develop new formats to accommodate new kinds of outputs from the GDACs.

Appendix Materials

All paper PHS 398 applications must provide appendix material on CDs 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

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 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/.

Additional Data Sharing Requirements Specific to this FOA to Address in the Data Sharing Plan.

All GCC and GDAC applicants must expressly acknowledge and agree that all data, datasets, algorithms, models, and protocols generated through the GCCs and GDACs will rapidly become available through TCGA for public use in accordance with the data release and sharing plan that was developed during TCGA pilot project (http://cancergenome.nih.gov/media/workshops.asp).  Sharing/dissemination of intellectual property should also be described in the Data Sharing Plan.  Please see the guidelines for the Data Sharing Plans below.

All data acquired by the awarded GCCs and GDACs must be made publicly available through the NCI.  The precise content of the data sharing plan may vary, depending on the data being collected. Nevertheless, all the TCGA awardees will be expected to adhere to the general data sharing principles established by the TCGA Pilot Project.  Applicants should include a description of the criteria for data evaluation, submission, and storage.  Applicants should describe briefly the expected schedule for data sharing, the format of the datasets, the documentation to be provided, and any analytic tools provided.  The NCI requires that throughout each GCC’s and GDAC’s funding period, all data, datasets, and algorithms be immediately released to the caBIG and other public databases (as appropriate) as they are generated and validated.  Algorithms and software tools must be released as open source consistent with caBIG principles.  A plan to release the data upon completion of the funding period is not acceptable.  Data submission release plans should aim for immediate automatic submissions once the data are verified.  In addition, each applicant should outline plans to store and maintain the anticipated large amounts of genomic data in-house on a temporary basis and propose appropriate arrangements with the caBIG for permanent storage and maintenance.

The reasonableness of the data sharing plan will be assessed by the reviewers.  The data sharing plan will not be a factor in the determination of scientific merit. 

Specific Instructions for Foreign Applications

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.

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 and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

The following will be considered in making funding decisions:

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a meritorious priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

The merits of the two types of applications solicited by this FOA (GCC applications and GDAC applications) will be assessed independently using the criteria listed below. Submitting (or not submitting) more than one type of application will not affect in any way the evaluation of these applications.

The following two sets of criteria will be used to assess GCC and GDAC applications:

Criteria for GCC Applications

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

In addition, specific to this FOA:

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, is the leadership approach, including the designated roles and responsibilities, governance, and organizational structure, consistent with and justified by the aims of the project and the expertise of each of the PDs/PIs?

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?

In addition, specific to this FOA:

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

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

Criteria for GDAC Applications

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

In addition, specific to this FOA:

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, is the leadership approach, including the designated roles and responsibilities, governance, and organizational structure, consistent with and justified by the aims of the project and the expertise of each of the PDs/PIs?

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?

In addition, specific to this FOA:

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

In addition, specific to this FOA:

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 rating:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan section on Human Subjects in the PHS 398 instructions).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan section on Human Subjects in the PHS 398 instructions).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five points described in the Vertebrate Animals section of the Research Plan will be assessed.

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

2.B. Additional Review Considerations

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

Applications from Foreign Organizations: Whether the project presents 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 will be assessed. 

2.C. Resource Sharing Plan(s)   

Relevant, reviewers will be instructed to comment on the reasonableness of the following Resource Sharing Plans, or the rationale for not sharing the following types of resources. However, reviewers will not factor the proposed resource sharing plan(s) into the determination of scientific merit or priority score, unless noted otherwise in the FOA. Program staff within the NCI will be responsible for monitoring the resource sharing.

3. Anticipated Announcement and Award Dates

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 Notice of Award. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

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 project 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 GCC and GDAC U24 awardees.  All the awardee institution(s), principal investigators (PI/PDs) and other key personnel must agree to collaborate on the goals of the Cancer Genome Atlas (TCGA) Research Network.

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

The PD/PIs will have primary responsibility for defining the specifics of the projects within the guidelines of this FOA and for performing all scientific activities. The PD/PIs must accept the close coordination of various aspects of scientific and technical management of the project by the TCGA Steering Committee and the NCI Project Scientists (outlined in the sections below).

The Principal Investigators will have the primary responsibility for:

Specific responsibilities of the GCCs and GDACs awardees will include:

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

2. A.2. NIH Responsibilities

A NCI Program Director(s) (acting as a Project Scientist(s)) will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. These NCI Staff Members will provide substantial input in terms of overall program coordination and directions and serve as voting members of the TCGA Steering Committee,

Additional NIH staff members (e.g., from the NCI Center for Biomedical Informatics and Information Technology, NCI CBIIT) may also have substantial involvement in the role of Project Coordinators.  The NCI staff (NCI Project Scientists, Project Coordinators)  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 NCI procedures for management of conflict of interest.

Additionally, an NCI Program Director(s) 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.

The NCI Project Scientist will:

The NIH reserves the right, with the advice of the TCGA Steering Committee, to suspend or reduce the award of those project participants who fail to share and disseminate data on a schedule established by the TCGA Steering Committee or who are judged by the Steering Committee to make insufficient progress in technology improvements.

2.A.3. Collaborative Responsibilities

TCGA Steering Committee. TCGA Steering Committee will serve as the main governing body of TCGA, including: (a) all awardees of the TCGA Research Network funded by the NCI (i.e., the GCCs and GDACs) and (b) Genome Sequencing Centers (GSCs) funded under the partner NHGRI initiative.  It is anticipated that the TCGA Steering Committee will provide strategic coordination for all activities of the Network.

GCC and GDAC awardees (as well as other voting members of the TCGA Steering Committee) will be required to accept and implement policies approved by the entire TCGA Steering Committee. It is anticipated that decisions for all appropriate activities will be reached by a consensus of TCGA Steering Committee and that NCI and NHGRI program staff will provide the input throughput this process. NCI and NHGRI retain rights to final approval of strategic decisions pertaining to the directions of the TCGA Research Network.

The activities of the TCGA Steering Committee will include the following:

TCGA External Scientific Committee.  The External Scientific Committee will be composed of senior scientists and clinicians with relevant expertise in cancer, genomics, bioinformatics and ethics; the members of the External Scientific Committee must not be PIs of a cooperative agreement involved in TCGA.  The External Scientific Committee may include appointed members as well as ad hoc members, as needed.

TCGA External Scientific Committee will offer input to NCI and NHGRI project leadership on specific scientific issues and overall progress of TCGA toward meeting its goals.  The External Scientific Committee will meet at least once per year; a portion of which will be held jointly with the TCGA Steering Committee.  The External Scientific Committee will contribute expertise and scientific insights on issues and questions as well as offer thoughts on overall progress and alterations to the activities of TCGA that might address specific short term problems and positively impact long term progress.

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:

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
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, Suite 243, MSC 7150
Bethesda, MD 20892-7150 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: 301-496-8634
Fax: 301-496-8601
Email: crystal.wolfrey@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/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.


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