Part I Overview Information

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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: Transdisciplinary Cancer Genomics Research: Post-Genome Wide Association (Post-GWA) Initiative (U19)

Announcement Type

New

Request For Applications (RFA) Number: RFA-CA-09-002

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

Key Dates
Release Date: January 12, 2009
Letters of Intent Receipt Date: April 29, 2009
Application Receipt Date: May 29, 2009
Peer Review Date: October/November, 2009
Council Review Date:January 2010
Earliest Anticipated Start Date: April 2010
Additional Information To Be Available Date (URL Activation Date): Not Applicable
Expiration Date: May 30, 2009

Due Dates for E.O. 12372

Not Applicable.

Additional Overview Content

Executive Summary

• Purpose. The purpose of this funding opportunity announcement (FOA), issued by the National Cancer Institute (NCI), is to promote thorough and efficient identification of genomic regions associated with cancer susceptibility. The FOA specifically solicits applications proposing transdisciplinary research projects designed to: a) take advantage of the existing Genome Wide Association Studies (GWAS) of cancer by exploiting previously generated “initial scan” GWAS data; and b) accelerate and coordinate integrative post-GWAS discovery research. To address these goals, each application should consist of two to three component sub-projects closely pertinent to a single unifying research theme. At least one of these sub-projects must address the replication or expansion of prior GWAS findings and at least one sub-project must center on epidemiologic aspects. In addition, biological and/or mechanistic studies complementing and connecting the required sub-projects are strongly encouraged as a third sub-project. The long-term goal is to provide a rigorous knowledge base that would enable clinical translation and public health dissemination of the GWAS findings. It is anticipated that these goals will require collaboration of multi-center teams comprising both epidemiologists and basic scientists.
• Mechanism of Support. This FOA will utilize the NIH Cooperative Agreement (U19) award mechanism.
• Funds Available and Anticipated Number of Awards. The NCI intends to commit up to $24 million in total costs in FY 2009, and up to $96 million over the planned 4-year project period, to support five to eight awards
• Budget and Project Period.  The total project period for applications submitted in response to this FOA may not exceed 4 years. 
• Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
• 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/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.
• Number of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs) may be designated on the application.
• Number of Applications. Applicants may submit only one U19 application per institution in response to this FOA..
• Resubmissions Resubmission applications are not permitted in response to this FOA
• Renewals Renewal applications are not permitted in response to this FOA. 
• Special Date(s). This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates
• Application Materials. See Section IV.1 for application materials.
• Hearing Impaired.  Telecommunications for the hearing impaired are available at: TTY 301-451-5936.

Table of Contents

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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

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Section I. Funding Opportunity Description

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1. Research Objectives

Purpose

The purpose of this funding opportunity announcement (FOA), issued by the National Cancer Institute (NCI), is to promote rigorous and efficient investigations on genomic variants tentatively implicated in cancer susceptibility to establish with confidence their significance in cancer. This post-Genome Wide Association (post-GWA) initiative specifically solicits applications proposing collaborative and transdisciplinary research projects addressing two overall goals:

1.     To pursue promising scientific leads from initial Genome Wide Association Studies (GWAS) of cancer (exploiting previously generated “initial scan” GWAS data); and

2.     To accelerate and coordinate integrative post-GWAS discovery research, which could provide the basis for expediting clinical translation and public health dissemination of the findings.

To address these goals, each application should consist of two to three component sub-projects closely pertinent to a single unifying research theme. At least one of these sub-projects must address replication and/or expansion of prior GWAS findings and at least one sub-project must center on related epidemiologic aspects. In addition, biological and/or mechanistic studies complementing and connecting the required sub-projects are strongly encouraged as a third component sub-project.

Because of the transdiciplinary nature, it is anticipated that these goals will require collaborative research involving multi-center teams comprising both basic scientists and epidemiologists. It is also expected that applicants will take advantage of the multiple Project Directors/Principal Investigators (multiple PDs/PIs) option.

Within the scope of this FOA, GWAS is defined as “any study of genetic variations monitored across the entire human genome that is designed to identify associations of specific genetic variants with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition.” This definition is consistent with that used in the NIH Guide Notice announcing the policy for sharing GWAS data (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html). Post-GWAS research phase is defined as the transition from the initial GWA discovery to replication studies, to the epidemiologic examination of gene-gene and gene-environment interactions, and to the biological validation of the GWAS findings.

All projects proposed in response to this FOA must address the post-GWAS phase of research efforts as outlined under Specific Research Objectives. These efforts should be well integrated to provide solid evidence on the significance of specific genetic variants in cancer. In the long run, this knowledge should provide a basis for the development of new clinical practices (e.g., in cancer diagnosis and treatment) and/or new cancer prevention strategies.

Studies proposing new “discovery” GWAS are NOT eligible for support under this FOA. Investigators planning new GWAS are encouraged to apply for investigator initiated research project grants (e.g., through the conventional unsolicited R01 applications).

Background

It has become increasingly apparent that genomic association studies provide a powerful method to detect the modest effects of high-frequency genetic variants that are involved in common cancer susceptibility. Initially, genotype-phenotype tests of association were limited to hypothesis-driven studies, which focused on a small number of candidate genes. However, recent advances in high-throughput molecular technologies, and the availability of the human genome sequence, have revolutionized researchers’ ability to catalogue human genetic variations. In addition, the international HapMap project has provided researchers with invaluable information regarding the linkage disequilibrium (LD) structure within the genome, thereby allowing for selection of haplotype tagging single nucleotide polymorphisms (SNPs). These remarkable advances have made large-scale GWAS practical. In 2007 alone, more than 150 studies, which have scanned the whole genome to search for genetic links to complex diseases, have been published. Numerous GWAS conducted to explore susceptibility to common cancers have led to identification of several genomic regions as putatively harboring cancer susceptibility alleles. Such alleles may be responsible for the majority of cancer burden attributable to genetic variants (as opposed to the cancer burden attributable to environmental factors). The effect of these alleles (in terms of cancer risk) is modulated by environmental factors, some of which can be consciously modified. Identification of genes whose variants are associated with cancer susceptibility is likely to uncover previously undetected (or underappreciated) regulatory mechanisms prompting further investigations on their roles in various types of cancer. This type of information is directly relevant to cancer risk assessment, early detection, prevention, drug development, and therapy.

Advances in genomics research have led to high expectations regarding their impact on health care and disease prevention. Still, premature use of GWAS-derived information for genetic testing may lead to confusion and possible harm in terms of public health. Therefore, it is imperative to accelerate the post-GWAS research phase, i.e., transition from the initial GWA discovery to replication studies and to the biological validation of the GWAS findings. Progress in post-GWAS research requires integrated efforts and transdisciplinary approaches.

Specific Research Objectives and Main Requirements

Consistent with the overarching goal of this FOA, all applications submitted in response to this initiative must be focused on the post-GWAS research on the significance of genomic variants in specific cancer types.

A. Tumor Types. Of primary interest are projects to study genetic variations in cancers of the breast, colon, prostate, pancreas, lung, melanoma, and bladder. Studies on other cancer types may also be appropriate.

However, for any cancer type selected, the proposed projects must meet the following preconditions:

a)     Availability of promising leads and substantial data from recent GWAS (i.e., from studies that have been published or will be published within 1 year of the U19 application submittal); and

b)     Existence of well-characterized populations of patient cases and controls, with detailed information on exposures and outcome ascertainment and available biospecimens.

Each proposed component must be based on existing initial GWA datasets used for either pooled analysis or meta-analysis. To qualify as appropriate (and correspond to the GWAS definition above, under “Purpose”), these datasets must have the density of genetic markers and the extent of linkage disequilibrium sufficient to capture a large proportion of the common variations in the genomes of the population under study. Moreover, the number of samples (in a case-control or trio design) should provide sufficient power to detect variants of modest effect.

In general, applications submitted in response to this FOA should be focused on a single cancer type. Nonetheless, it is expected that covering more than one tumor type could be of value in certain situations (e.g., when leads for a specific association exists for two tumor types). Thus, applicants may propose studies involving more than one tumor type, but only when such an approach benefits the overall project (a strong justification must be provided).

B. Required Research Components. Reflecting the transdisciplinary nature of this FOA, each applicant team is strongly encouraged to propose interrelated component sub-projects, which address all the three main areas identified below. Examples of research pertinent to these three areas include (but are not necessarily limited to) the following types of studies:

Area 1. Discovery Expansion and Replication

1. Finding of new associations through pooled or meta-analyses
2. Independent replication studies to confirm genotype-phenotype associations
3. Fine mapping of association signals

Area 2. Biological Studies

1. Identification of risk-enhancing genetic variants
2. Examination of functional consequence of a genetic variant
3. Determination of biological mechanisms of risk enhancement

Area 3. Epidemiologic Studies

1. Evaluation of gene-gene and gene-environment interactions
2. Assessment of penetrance and population attributable risk
3. Development of complex risk models
4. Evaluation of clinical/analytic validity of risk models in observational studies

Note: Component sub-projects dedicated to Area 1 and Area 3 are the required minimum for applications to be responsive to this FOA. Applicants should be aware, however, that proposing well-integrated sub-projects in all three areas may enhance the overall merit of their applications.

The following types of analytical methods and approaches are expected to be used in the proposed projects:

• Pooled analyses in which multiple “initial GWAS scans” are combined will increase the power of individual GWAS to detect smaller genetic effects or less frequent causal variants. In addition to novel loci of cancer risk, the increased sample size of these pooled analyses means additional phenotypes such as risk of relapse, second cancers or disease severity could be considered using existing data.
• Replication studies are essential to validate previously reported genotype-phenotype associations, particularly in light of the increased rate of false positive results in GWAS due to multiple testing. Both pooled analyses and replication studies need to be performed in a timely and coordinated fashion, and usually involve a large number of institutions. Therefore, particular attention to quality control and data harmonization will be required.
• Fine-mapping studies are necessary to narrow the associated genomic region of interest, and functional studies are essential in order to identify the true causal variant. For example, several reported genotype-phenotype associations localize to regions with no readily identifiable genes, making interpretation challenging.
• Once a susceptibility allele is identified, functional studies are desirable to provide insights into the mechanism of increased risk. These studies can be performed using either cultured cells or animal models.
• Gene-gene interactions and pathway analyses will incorporate multi-gene models to investigate the effects of environmental risk factors.
• Epidemiologic studies will evaluate gene-gene and gene-environment interactions and their association with clinical parameters. This information will be then incorporated into risk models. These studies will be essential to understanding whom to target with public health or clinical interventions, and to translate these results into effective preventive or therapeutic interventions.

C. Data Sharing. To maximize scientific benefits and impact of the program, all Post-GWA Initiative U19 applicants must agree to data sharing requirements as outlined in Section IV. 6. Other Submission Requirements, including the compliance with the general NIH policy for sharing GWAS-related data (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html). Proposed bioinformatic approaches must comply with these requirements, additionally including (but not limited to) the use of and compatibility with the NCI's cancer Biomedical Informatics Grid (caBIG) and/or Center for Biomedical Informatics and Information Technology (CBIIT) for data dissemination.

D. Effort Integration and Post-GWA Initiative Governance. Research supported by this FOA is expected to be complementary and synergistic with other major NCI initiatives such as the Cancer Genome Anatomy Project (CGAP), the Early Detection Research Network (EDRN), the Comparative Systems Genetics of Cancer (CSGC), the Centers for Population Health and Health Disparities (CPHHD), the Mouse Models of Human Cancer Consortium (MMHCC) and the Genes, Environment and Health Initiative (GEI). In their strategic planning, applicants responding to this FOA are encouraged to take advantage of the existing resources provided by these programs, and, reciprocally, should avoid effort duplication.

Post-GWA Initiative Steering Committee (SC). To facilitate the integration of efforts sponsored by the Post-GWA Initiative, awardees (with the participation of the NCI) will form a Steering Committee (SC) as the trans-initiative coordinating and governing body. It is expected that SC will: (a) promote interactions among individual awardees; (b) coordinate efforts; (c) facilitate collaborations if appropriate; and (d) facilitate access to other resources and interactions with other relevant NCI-sponsored programs. Applicants should plan for their participation in these activities.

Awardees will be required to participate in two meetings of the Post-GWA Initiative per year. These events will comprise: (a) SC meetings; and (b) broad meetings that will be open to the representatives of the awardees, the NIH extramural staff, and intramural collaborators (as appropriate).

These Post-GWA Initiative meetings are intended to provide a scientific forum for:

• Updates on the awardees’ research, exchanging ideas and information, and discussing collaborations among the Post-GWA Initiative awardees (across awardee institutions) and with outside investigators;
• Identifying the group's tangible resources, capabilities, and needs to advance overall Post-GWA Initiative goals; and
• Oral presentations by the lead PIs of each Post-GWA Initiative award on project progress and current and planned activities.

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

Section II. Award Information

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1. Mechanism of Support

This funding opportunity will use the NIH Cooperative Agreement (U19) award mechanism. The Project Director(s)/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 PD(s)/PI(s) retain(s) 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 PD(s)/PI(s), as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award." 

2. Funds Available

The NCI intends to commit approximately $24M for FY 2009 to support of five to eight awards. Future year amounts will depend on annual appropriations. The duration of each award will be 4 years. Budget requests should not exceed $3M in total costs during any year.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the NCI provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

Facilities and administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

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

Section III. Eligibility Information

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1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

• Public/State Controlled Institutions of Higher Education;
• Private Institutions of Higher Education;
• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education);
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education);
• Small Businesses;
• For-Profit Organizations (Other than Small Businesses);
• State Governments;
• U.S. Territories or Possessions;
• Eligible Agencies of the Federal Government; and
• Units of Local Governments.

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(s) to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs. Given that transdiciplinary efforts are necessary for projects proposed in response to this post-GWA initiative, applicants are strongly encouraged to take advantage of the multiple PDs/PIs option.

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).

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

Applicants may not submit resubmission applications in response to this FOA.

Applicants may not submit renewal applications for this FOA. 

Applicants may submit only one U19 application per institution in response to this FOA. However, if appropriate and desirable, investigators from an institution submitting an U19 application in response to this FOA may participate as collaborators on an U19 application from another institution.

Whereas foreign institutions are not eligible to submit application under this FOA, eligible U.S. applicant institutions may propose subcontractual arrangements with Foreign institutions.

Applicants are strongly encouraged to use this option and include foreign investigators as collaborators and full participants of the transdiciplinary team. However, if the collaboration involves the inclusion of a foreign population of patients/participants, justification of its relevance to the overall purpose of the study must be included.

Section IV. Application and Submission Information

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1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance, contact GrantsInfo -- Telephone: (301) 710-0267; Email: GrantsInfo@nih.gov.

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

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms 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

Post-GWA Initiative U19 applicants must demonstrate in the application their ability to meet:

• Research Objectives defined in Section I of the FOA;
• Data sharing requirements as outlined in Section IV. 6. Other Submission Requirements; and
• Other investigator responsibilities described in Section VI.2.A Cooperative Agreement Terms and Conditions of Award.

SUPPLEMENTARY 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).

Use additional Form Pages 4 and 5 to provide separate budget information for the following individual application components:

• A detailed budget (direct costs) for the Administrative Core (first year and a cumulative budget for the entire project period); and
• Detailed separate budget pages for each component sub-projects (first year and cumulative budgets for the entire project period).

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:

• Standard Items 2-5 of the PHS 398 Research Plan are replaced by the new Sections N1-N4 (specified below).
• The PHS 398 standard page limit for Items 2-5 is replaced by a new limit of 20 pages for the new Sections N1, N3, and N4. For the Section N2, the limit is 20 pages per each component sub-project proposed (i.e., 40 or 60 pages for two or three subprojects, respectively).

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.

Section N1. Overall Description of the post-GWA Project (up to 10 pages suggested)

Present the overall vision for the proposed post-GWA Project including the following segments:

• Long and short-term scientific objectives, specifically addressing the strategic goals and main scientific requirements of the post GWA initiative;
• Background on the leads from prior GWAS that provide the foundation for the proposed post-GWA studies;
• The unifying theme and scientific integration of the proposed component sub-projects; and
• Relevance of the proposed studies to other NCI programs.

Section N2. Individual Component Sub-projects (limited to 20 pages per each sub-project).

Each application should consist of two to three component sub-projects closely pertinent to a single unifying research theme. Each applicant team is strongly encouraged to propose interrelated component sub-projects that address all the three main areas identified in Section II. Research Objectives.

As a minimum, each application must consist of one sub-project dedicated to Area 1 and another sub-project dedicated to Area 3. Applicants should be aware, however, that proposing interrelated sub-projects in all three areas may enhance the overall merit of their applications.

Describe each research project in sufficient detail to enable reviewers to judge its scientific merit.  The description of each component sub-project must contain the following elements:

Sub-project Face Page containing sub-project title, name of Sub-project Leader/PI, Project Summary and Key Personnel (listing percent of effort of each individual);

Research Plan to include the following items (analogous to standard Items 2-5 in the PHS 398 instructions):

i.    Specific Aims;

ii.    Background and Significance;

iii.    Preliminary Studies; and

iv.    Research Design and Methods.

Section N3.  Project Organization (Administrative Core, up to 5 pages suggested).

It is expected that each awardee will organize an administrative core to support and coordinate project administration across the participating institutions and to interact with the Post-GWA Initiative SC.

In this section, describe administrative structure to support the proposed post-GWA Project.  Define: (a) the organization of the leadership structure; (b) effort distribution across the participating institutions; and (c) any joint activities that will involve investigators from all participating institutions (meetings, teleconferences, etc.), and the coordination of trans-initiative activities (Steering Committee activities, semi-annual Post-GWA Initiative meetings, etc.). Note that if the multiple PD/PI option is used, applicants must also complete Item 14 “Leadership Plan” of the PHS 398 Research Plan (avoid duplication).

Describe the coordination of bioinformatics efforts across the participating institutions. Outline vision for the interaction in this regard with other Post-GWA Initiative awardees and the NCI.

Post-GWA trans-initiative activities. Plans should be made (and appropriate funds budgeted) for the participation in activities shared with other awardees of the Post-GWA Initiative, including (but not limited to):

• Participation in the activities of the Post-GWA Initiative SC (monthly teleconferences and twice-a-year face-to-face meetings).
• Participation in two meetings of the Post-GWA Initiative per year. See Section IV.6. Other Submission Requirements for details.
• Participation in program evaluation activities. Each post GWA Initiative awardee and the entire program will be periodically evaluated by the NCI. Applicants should acknowledge their readiness to participate in and facilitate such evaluation. 

Section N4. Critical Resources and Capabilities (up to 5 pages total suggested)

Describe briefly the critical resources and capabilities available to the project. These resources must be in place by the time of the proposed project start. Applicants should take maximal use of the existing resources, institutional cores, etc. No duplication of existing NIH-funded shared resource cores will be allowed.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs  

Applications must use the multi-P.I.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: April 29, 2009
Application Receipt Date: May 29, 2009
Peer Review Date: October/November, 2009
Council Review Date: January 2010
Earliest Anticipated Start Date: April 2010

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(s), address(es), and telephone number(s) of the PD(s)/PI(s);
• 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 addressed and sent to:

Daniela Seminara, Ph.D., M.P.H.
Epidemiology and Genetics Research Program
Division of Cancer Control and Population Sciences
National Cancer Institute (NCI)
6130 Executive Boulevard, EPN Room 5142, MSC 7395
Bethesda, MD 20892-7395 (for U.S. Postal Service Express or regular mail)  
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 594-7347
Fax: 301-435-6609
Email: seminard@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 (for U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for non-USPS delivery)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Referral Officer
National Cancer Institute
Division of Extramural Activities
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329 (for U.S. Postal service Express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-3428
FAX:  (301) 402-0275
Email: ncirefgrp@mail.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 a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project (see the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.)

6. Other Submission Requirements and Information

The PDs/PIs of awarded Post-GWA Initiative U19 projects will convene twice a year throughout the project life in order for the steering committee to meet as well as to discuss challenges/progress and share findings. All applicants should budget for these travel expenses. For the purposes of estimating budgets, at a minimum all PIs and key scientific personnel should plan on two 2-day meetings each year, alternating between near the NIH Bethesda, MD, campus and a location to be determined.

Awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A. Award Administration Information.

Appendix Materials

All paper PHS 398 applications submitted must provide appendix material on CDs only. Include five identical CDs in the same package with the application. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html.

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community.  If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application.  See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

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

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

(c) Genome-Wide Association Studies (GWAS):  Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible.  A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition.  For further information, see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

Additional Data Sharing Requirements Specific to Post-GWA Initiative

Even though this FOA will not support new GWAS, data sharing will be mandatory for all Post-GWA Initiative U19 awardees. In addition to data sharing terms defined in the NIH-wide policies (see items “a” and “c” above), supplementary requirements specific to this FOA are as follows.

It is expected that data generated by the studies funded by the Post-GWA Initiative (e.g., genotyping, fine mapping, and other data) will be made publicly available. The release for sharing should take place as soon as the data have passed appropriate data quality assessments, and a moratorium period (not to exceed 9 months) has elapsed.

The expected route for data dissemination is the NCI's cancer Biomedical Informatics Grid (caBIG). Investigators may share data via caBIG’s caGrid utilizing tools, developed by either the caBIG community or other caBIG-compliant software.  Alternatively, data may be submitted to the NCI Center for Biomedical Informatics and Information Technology (CBIIT) for dissemination through an NCI-hosted version of caGWAS. Controlled access to pre-computed summary data, including SNP frequencies and simple unadjusted single SNP association analyses, must be made available, and should be budgeted for.

Budgetary requests in U19 applications submitted in response to this FOA may include funds to support local efforts for standardizing or harmonizing phenotypes and exposure data, registering the harmonized elements within caBIG, as well as coordination of genotype, phenotype, and exposure data sharing within caBIG.

In planning data sharing and dissemination, the applicants should take into account the following considerations. Controlled access to individual genotype data, as well as individual phenotype and exposure data will be available for approved research purposes through a Data Access Committee (DAC) to be organized jointly by the NCI and the Post-GWA Initiative Steering Committee. The Data Access Committee will have balanced representation drawing from the PIs from the awarded projects, NCI staff, and external scientists with internationally recognized expertise in the area of post-GWA research continuum. These external experts will be nominated and appointed by common agreement of the NCI and the Post-GWA Initiative SC. External scientists must not be associated with awarded institutions. Interested researchers will be required to complete a “Data Use Certification” that will include a brief description of the proposed research use, and confirmation that the proposed research use is consistent with any constraints identified by the Study Investigators who submitted the data.

It is expected that in addition to experimental data and related metadata, post-GWA U19 awardees will also share with qualified investigators other high-quality documentation (e.g., protocols, manuals, etc.) that might be needed to facilitate the use of primary data.

Section V. Application Review Information

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1. Criteria

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

2. Review and Selection Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NCI and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

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

• Undergo a selection process in which only those applications deemed to have the highest scientific and technical 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 National Cancer Advisory Board.

This award will include special terms and conditions that differ from the agency's usual terms and conditions.  See also Section IV.5, “Funding Restrictions.”

The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by peer review;
• Availability of funds;
• Relevance of the proposed project to program priorities; and
• Compliance with resource sharing policies.

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

A. Criteria for Overall Evaluation of Post-GWA Initiative Application as Integrated Effort:

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

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

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

In addition, specific to this FOA:

• How likely are the proposed studies to provide conclusive information on the significant associations of specific genomic regions with cancer susceptibility?
• Do the proposed studies have the potential to expedite translation of existing putative GWA leads into clinical practice and/or public health applications?

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

In addition, specific to this FOA:

• Is the composition of the applicant team appropriate for collaborative transdiciplinary research intended to validate with confidence tentative GWA leads? Are both epidemiologists and basic scientists adequately represented for the proposed projects?

Innovation.  Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions?  Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense?  Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

In addition, specific to this FOA:

Is the proposed research innovative in terms of enhanced potential for findings that would not be likely without the coordinated team effort of scientists representing different fields?

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

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

In addition, specific to this FOA:

• How strong is the rationale to pursue genetic variants in the proposed cancer type(s)? Are appropriate leads available from recent GWAS?
• Are the proposed studies based on well-characterized populations of patient cases and controls with detailed exposures and outcome ascertainment and available biospecimens?
• Do the proposed sub-projects adequately address research areas identified as essential for post-GWAS efforts? How well are these sub-projects integrated? Are these sub-projects taken together sufficient to establish with confidence the causality of tentatively identified genomic regions in terms of cancer risk?

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

In addition, specific to this FOA:

Is there sufficient evidence of significant commitment of the participating institutions and documentation of available critical resources needed to fulfill the objectives of the Post-GWA Initiative?

Additional criterion specific for this FOA:

Integration: Is there evidence of scientific and administrative integration of the proposed U19 program?  Is there evidence of coordination, interrelationships, and synergy among the individual research projects and administrative core?  Are there clear advantages or “value added” by conducting the proposed research as an integrated effort rather than through separate research efforts?

B. Criteria for Component Sub-projects.

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

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

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

Investigator(s).  Are the PD/PIs, collaborators, and other researchers well suited to the project?  If Early Stage Investigators or New Investigators, do they have appropriate experience and training?  If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)?  If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation.  Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions?  Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense?  Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach.  Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project?  Are potential problems, alternative strategies, and benchmarks for success presented?   If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

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

C. Criteria for Administration/Administrative Core. Is the organizational, scientific, and operational framework reasonable, well integrated, and appropriate for the objectives of the Post-GWA Initiative? 

2.A. Additional Review Criteria:

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

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

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

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

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

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

2.B. Additional Review Considerations

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

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

2.C. Resource Sharing Plan(s)

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable:

1) Data Sharing Plan (http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm);

2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and

3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

Reviewers will also be asked to comment on the adherence to additional specific requirements related to data sharing identified in Section IV. 6. Other Submission Requirements (Resource Sharing Plan).

3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information

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1. Award Notices

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

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

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

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

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).
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 Post-GWA Initiative U19 awardees.  All the awardee institution(s), principal investigators (PI/PDs) and other key personnel must agree to collaborate on the goals of the Post-GWA Initiative.

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

The Principal Investigators will have the primary responsibility for:

• Defining the research plan and goals;
• Overseeing/performing the scientific activities of the plan;
• Monitoring the completion of milestones within the timeframe and budget proposed; and
• Cooperating with NCI programmatic, technical, and administrative staff; and administratively managing the U19.

Specific rights and responsibilities of awardees will include the following:

• Each U19 awardee must designate two representatives to serve as voting members of the across-study Post-GWA Initiative Steering Committee (SC). Both representatives could be PDs/PIs (if the multiple PD/PIs option is used) or the PD/PI and another designated senior investigator.
• These and/or other awardee representatives will participate as required on any committees or working groups that may be established by the SC during the course of the project.
• All awardees must agree to abide by the decisions of the SC and follow the policies and procedures developed by the SC.
• The PD(s)/PI(s) will be responsible for providing an annual progress report and other information on study progress as might be needed.
• 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 during the entire project period.
• However, awardees will have to adhere to data and resource sharing plans and policies as defined in this FOA. Thus, the awardees must be committed to making research samples and tools, methods, data, and materials that they develop under their awards to other Post-GWA Initiative awardees and to the general research community.
• The PDs/PIs will be responsible for ensuring that respective data/resources are shared in a timely fashion and in the proper manner (through the NCI caBIG and/or Center for Biomedical Informatics and Information Technology, CBIIT) for dissemination through an NCI-hosted version of caGWAS.
• Controlled access to pre-computed summary data, including SNP frequencies and simple unadjusted single SNP association analyses, must be made available (to qualified external investigators to be granted by the Post-GWA Initiative Data Access Committee).
• Controlled access to individual genotype data, as well as individual phenotype and exposure data must be provided for approved research purposes.
• PDs/PIs on each award will be responsible for forming an appropriate Data Access Committee and then overseeing its operation. It is expected that outside investigators will complete a Data Use Certification, which will include a brief description of the proposed research use and confirmation that the proposed research use is consistent with any constraints identified by the Study Investigators who submitted the data. In addition to experimental data and related metadata, the awardees will be expected to provide additional high-quality documentation (protocols, manuals, etc) that might be needed for outside researchers to take full advantage of the shared data.
• PIs and other representatives of the awardees will participate in two cross-study meetings per year of the post-GWA-Initiative.
• Participation in program evaluation activities. Each post GWA Initiative awardee and the entire program will be periodically evaluated by the NCI. Applicants should acknowledge their readiness to participate in and facilitate such evaluation.

2. A.2. NIH Responsibilities

Two designated NCI Program Directors acting as NIH Project Scientists will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. Additional NCI staff members (e.g., from the NCI Center for Biomedical Informatics and Information Technology, NCI CBIIT) may also have substantial involvement as Project Coordinators.  The NCI Project Scientists and the NCI 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 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 main NCI responsibilities pertinent to the Post-GWA Initiative U19 awards include the following activities:

• In conjunction with other NCI scientific program staff members and the Post-GWA Initiative Steering Committee (SC) (see below), the appointed Project Scientists will provide advice and guidance on technical issues, such as reviewing progress or recommending changes.
• The NIH Project Scientists/Coordinators may also participate in the design of research activities; advise on the availability of resources pertinent to the project; coordinate or participate in the collection and/or analysis of data; or advise on the management and technical performance.
• The NCI Project Scientists/Coordinators will facilitate the process of data dissemination/sharing by coordinating the awardees efforts with the NCI CBIIT and the caBIG™ project.
• The NIH Project Scientists will serve as voting members of the SC.
• The NIH Project Scientists will assist the SC in forming  the Data Access Committee and will serve as voting members of the Data Access Committee;
• The NCI Project Scientists will assist the SC in developing and drafting operating policies;
• The NIH Project Scientists and Project Coordinators will provide scientific and administrative cross-studies coordination of the efforts of all the Post-GWA Initiative awardees.
• The NIH Project Scientists and Project Coordinators will assist the SC in organizing the semi-annual meetings of the Post-GWA Initiative;
• The NCI Project Scientists and the NCI Project Coordinators will review the scientific progress of individual Post-GWA Initiative U19 awardees and their compliance with the operating policies developed by the SC;
• To assess the performance of individual awardees, the NIH Project Scientists will review annual reports, conduct site visits, and take other actions as needed; and
• The NCI Project Scientists may recommend withholding of support, suspension, or termination of a U19 award for lack of scientific progress or failure to adhere to policies established by the SC.

2.A.3. Collaborative Responsibilities

The NCI Project Scientists and the PD/PIs of the Post-GWA Initiative U19 awards will be responsible for forming an across study Post-GWA Initiative Steering Committee (SC), the main governing body of the Post-GWA Initiative, as defined below.

• The Steering Committee will be composed of the following voting members:  The two designated representatives of each Post-GWA Initiative U19 research project awardee (who could include two PD/PIs, if the multiple PD/PI option is used, or the PD/PI and another senior scientist); and two NCI Project Scientists. Each full member will have one vote.
• The Project Coordinators from each NCI Extramural Division and the NCI CBIIT will be non-voting members of the Steering Committee.  One or more patient advocates may also be included as non-voting members of the Steering Committee. 
• The SC Chair and Co-Chair will be elected by majority vote at the first SC meeting. The SC chairperson(s) may not be an NCI representative.  Chairperson will rotate every year.
• The SC may establish sub-committees, as it deems appropriate.  The NCI Project Scientists/Coordinators will serve on sub-committees, as they deem appropriate.
• The SC will meet monthly by teleconference and twice every year, at locations selected by the NCI in consultation with the SC.
• The SC may, when it deems it to be necessary, invite additional, non-voting science advisors to the meetings.  The NCI reserves the right to propose such additional candidates to augment the research when necessary.

The responsibilities of the Post-GWA Initiative SC include the following:

• Evaluate progress of the Post-GWA Initiative projects and provide guidance;
• Work with PDs/PIs to establish goals and promote collaborations among members of the Post-GWA Initiative;
• Ensure the timely release of data to NIH-supported and/or public databases; and
• Assist, as required, in preparing formal reports summarizing activities and/or progress; and
• Organize together with the NCI staff members the semi-annual Post-GWA Initiative meetings

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.

The final Non-Competing Continuation Grant Progress Report for the project period must contain a list of all publications that result from the funding of the U19 research award.

Section VII. Agency Contacts

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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 Seminara, Ph.D., M.P.H.
Epidemiology and Genetics Research Program
Division of Cancer Control and Population Sciences
National Cancer Institute (NCI)
6130 Executive Boulevard, EPN Room 5142, MSC 7395
Bethesda, MD 20892-7395 (for U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 594-7347
Fax: 301-435-6609
Email: seminard@mail.nih.gov

Elizabeth Gillanders, Ph.D.
Host Susceptibility Factors Branch
Division of Cancer Control and Population Sciences
National Cancer Institute (NCI)
6130 Executive Boulevard, EPN Room 5140, MSC 7393
Bethesda, MD 20892-7324 (for U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 594-5868
Fax: 301-435-5477
Email: lgilland@mail.nih.gov

2. Peer Review Contacts:

Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-3428
FAX: (301) 402-0275
Email: ncirefof@dea.nci.nih.gov

3. Financial or Grants Management Contacts:

Crystal Wolfrey
Office of Grants Administration
National Cancer Institute
6120 Executive Boulevard, EPS Room 2433, MSC 7150
Bethesda, MD 20892-7150 (For U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-8634
FAX:  (301)496-8601
Email: wolfrey@@mail.nih.gov

Section VIII. Other Information

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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.
Investigators are expected to have access to phenotypic data and sources of DNA from existing study populations of sufficient size at the time that the application is submitted to adequately address the specific aims.