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: Strategic Partnering to Evaluate Cancer Signatures [SPECS II] (U01)

Announcement Type
New

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

• March 14, 2011 - This PAR has been reissued as PAR-11-151.
• February 23, 2011 The Expiration Date for this announcement has been changed to May 8, 2011 per NOT-OD-11-048, which redefines the U01 activity code and announces the transition of U01 applications to electronic submission through Grants.gov using the SF424 (R&R) forms for due dates on or after May 25, 2011.

Program Announcement (PA) Number: PAR-10-126

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

Key Dates
Release Date: March 8, 2010
Letters of Intent Receipt Dates: May 15, 2010; May 15, 2011, May 15, 2012
Application Receipt Dates: June 15, 2010, June 15, 2011, June 15, 2012
AIDS Application Receipt Dates: Not Applicable
Peer Review Dates: November 2010, November 2011, November 2012
Council Review Dates: January 2011, January 2012, January 2013
Earliest Anticipated Start Dates: April 2011, April 2012, April 2013
Additional Information To Be Available Date (Activation Date): Not Applicable.
Expiration Date:(Now Expired March 15, 2011 per issuance of PAR-11-151); Previously Changed to May 8, 2011 (Per NOT-OD-11-048); Original Date June 16, 2012

Additional Overview Content

Executive Summary

• Purpose. This Funding Opportunity Announcement (FOA), issued by the National Cancer Institute (NCI) of the National Institutes of Health (NIH), encourages the submission of grant applications for support of the clinical application of multi-analyte molecular signatures derived from comprehensive molecular annotation of tumors. There is growing recognition in the clinical cancer research community that annotation of tumor specimens with data that integrates information about molecular alterations at the levels of DNA, RNA, and protein provides not only a more complete understanding of tumor biology but also provides a significant opportunity for developing new clinical tools to improve cancer treatment. Translating the knowledge gained from this molecular annotation into tools that can be used in clinical decision-making remains a major challenge. The purpose of this initiative is to build on recent demonstrations that molecular signatures correlate with important clinical parameters in cancer. The goal of this initiative is also to create publications and data sets that will be available and accessible to the scientific community in order to further the development, design, and conduct of future clinical trials (e.g., incorporation of molecular signatures into future clinical trials and large clinical validation studies) and to encourage appropriate commercialization to benefit the public health. The NCI invites investigators to form strategic partnerships that will bring together the multi-disciplinary expertise and resources needed to determine how the information derived from comprehensive molecular analyses can be used to improve patient care and, ultimately, patient outcomes.
• Mechanism of Support. This FOA will utilize the NIH U01 cooperative agreement mechanism.
• Funds Available and Anticipated Number of Awards. Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.
• Budget and Project Period. The total project period for an application submitted in response to this funding opportunity may not exceed 5 years.
• Application Research Strategy Length: The U01 Research Strategy section may not exceed 12 pages, including tables, graphs, figures, diagrams, and charts. See Table of Page Limits.
• 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 more than one application, provided that each application is scientifically distinct.
• Resubmissions. Applicants may submit a resubmission application, but such application must include an Introduction addressing the previous peer review critique (Summary Statement). See new NIH policy on resubmission (amended) applications (NOT-OD-09-003, NOT-OD-09-016).
• Renewals. Applicants may not submit a renewal application.
• Special Date(s). This FOA uses non-standard due dates. See Receipt, Review, and Anticipated Start Dates.
  • See Section IV.1 for application materials.
• Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY (301) 451-5936.

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

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. Dispute Resolution
3. Reporting

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

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Purpose

This Funding Opportunity Announcement (FOA), issued by the National Cancer Institute (NCI), of the National Institutes of Health (NIH), encourages grant applications for the clinical application of multi-analyte molecular signatures derived from comprehensive molecular annotation of tumors. There is growing recognition in the clinical cancer research community that annotation of tumor specimens with data that integrates information about molecular alterations at the levels of DNA, RNA, and protein provides not only a more complete understanding of tumor biology but also provides significant opportunities for developing new clinical tools to improve cancer treatment. Translating the knowledge gained from this molecular annotation into tools that can be used in clinical decision-making remains a major challenge. The purpose of this initiative is to build on recent demonstrations that molecular signatures correlate with important clinical parameters in cancer. The goal of this initiative is also to create publications and data sets that will be available and accessible to the scientific community in order to further the development, design, and conduct of future clinical trials (e.g., incorporation of molecular signatures into future clinical trials and large clinical validation studies) and to encourage appropriate commercialization to benefit the public health. The NCI invites investigators to form strategic partnerships that will bring together the multi-disciplinary expertise and resources needed to determine how the information derived from comprehensive molecular analyses can be used to improve patient care and, ultimately, patient outcomes.

This FOA will utilize the NIH U01 cooperative agreement mechanism.

Background

Molecular Annotation of Tumors. Through the molecular annotation of tumor specimens, investigators have been able, in retrospective studies, to identify subgroups of patients who have the same diagnosis but have different clinical outcomes. Investigators have had limited success in using standard tumor classification systems to identify such subgroups. The challenge is to translate the information in these molecular signatures into useful assays that can be applied in clinical practice. To meet this challenge, signatures must be confirmed in independent studies. Critical elements of signatures that correlate most strongly with the clinical endpoint of interest must be identified and confirmed. Robust assays suitable for use in the clinical setting must be developed and validated. This iterative process of signature refinement and confirmation and clinical assay development requires diverse scientific and technical expertise and access to significant patient and tissue resources.

Cancer Diagnosis Program and Program for the Assessment of Clinical Cancer Tests. The overall goals of the Cancer Diagnosis Program (CDP) and its Program for the Assessment of Clinical Cancer Tests (PACCT) are to develop more informative laboratory tools to help maximize the benefit of cancer treatments and to ensure the efficient and effective translation of these tools to the clinic. Significant barriers to development, identified by the PACCT Strategy Group, include the difficulty of designing studies with sufficient power to address the hypotheses posed; the need for large numbers of well defined and annotated cases or specimens with long periods of follow-up; a need for standardization of reagents and assay procedures to facilitate comparison of data from multiple studies; and complicated intellectual property (IP) issues that result in tests that cannot be performed for acceptable costs. In order to overcome these barriers, PACCT has defined a pathway for bringing new markers/technologies to the clinic and developed draft guidelines for marker development. The biggest barrier is encountered when large studies need to be performed that by necessity are multi-institutional and multi-disciplinary. The present initiative is designed to address this need. We need to keep the development pipeline flowing by encouraging well-designed studies funded appropriately in a way that will allow investigators to assemble the requisite expertise and the appropriate clinical materials, do the necessary analytical validation of their signatures, and then assess the clinical utility.

Advances in the Previous SPECS Program Funding Period. This FOA is designed to build upon the successes and lessons learned in the original Strategic Partnering to Evaluate Cancer Signatures (SPECS) Program. The SPECS Program has successfully demonstrated that assembling a research team with all of the required expertise for translating a potential diagnostic signature to a clinical assay greatly accelerates the movement of knowledge to clinical application. All six projects of the original SPECS Program have developed signatures that are either being considered for inclusion in clinical trials or are rapidly moving toward clinical validation. The involved investigators have also demonstrated, either within their own projects or as part of the childhood cancer research program called the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) Program (http://target.cancer.gov/), that the integration of molecular data from multiple analytical platforms significantly increases our understanding of both the disease process and the potential clinical utility of these signatures. The NCI intends to continue to provide resources in order to take advantage of new opportunities to move additional multi-analyte signatures toward clinical application.

Specific Research Objectives for SPECS II

The projects funded through this FOA are intended to exploit the successes of the many research projects applying comprehensive molecular analyses to the study of cancer. Comprehensive molecular analysis provides a snapshot of the biological state of a tumor. The challenge is to move beyond the initial discovery of potentially useful profiles, to decide which subset of the elements in the profile needs to be measured, to confirm that the profiles are robust and can be reproducibly measured, and to evaluate the clinical utility of the profiles in clinical trials or other large datasets. Meeting this challenge requires the dedicated cooperation of not only clinicians and laboratory investigators, but also biostatisticians and experts in bioinformatics.

Research topics of interest include but are not limited to:

Applicants will be asked to describe the clinical question(s) or need(s) to be addressed for the benefit of a specific set of cancer patients with one or a closely related set of tumors (i.e., cancer types). These questions may include, but are not limited to:

• Prognosis for the patient at the time of diagnosis;
• Risk of progression in early stage disease;
• Identification of subsets within a tumor classification, stage, or grade where there is known heterogeneity in clinical behavior, including response to treatment with standard drugs or radiation therapy; and
• Prediction of response to targeted therapies.

The questions posed should address a well-defined clinical need so that, if the project is successful, molecular signatures or their derivatives can be considered in planning treatment for individual patients.

Definition of Multi-Analyte Signatures. This initiative will support new projects that have identified multi-analyte and prognostic and/or predictive signatures and are ready to bridge the gap between discovery of signatures and their integration into clinical practice. For the purpose of this FOA, multi-analyte signatures are defined as signatures that result from the measurement of more than one molecular entity. Those molecular entities may be levels of gene or microRNA expression, or genomic alterations including DNA amplifications, deletions, translocations, mutations, single nucleotide polymorphisms (SNPs), and epigenetic events, or levels of protein expression or modifications. The signatures proposed for clinical assay development may consist of multiple examples of a single analyte type or any combination of analytes that have been demonstrated to correlate with clinical parameters of interest.

Intended Scope of the Projects. Applicants will be asked to propose projects that will develop new clinical laboratory assays in the context of clinical needs of a specific group of cancer patients with one or a related set of tumors. Applicants are encouraged to study multi-analyte molecular signatures that have already been shown to address a clinical question(s) or need(s). The proposed studies should be designed to confirm and refine these signatures in order to demonstrate their clinical utility. Applicants are expected to have established the collaborations necessary to bring together all of the expertise and clinical resources required to achieve project goals. It is anticipated that these will be multi-institutional projects involving investigators with expertise in technology development and application, cancer biology, oncology, pathology, clinical cancer research, assay development, biostatistics, and bioinformatics. These collaborations are expected to involve already existing organizations with access to patients or patient specimens (see Tissue Resources, below).

Applicants are encouraged to propose projects that build on previously identified molecular profiles. They are asked to propose evaluation of the potential clinical usefulness of molecular signatures that have already been developed using a variety of molecular analysis technologies, including DNA, RNA, or protein technologies. Applicants may propose to define critical components in the signature, to confirm that the selected components continue to provide the desired clinical information and to develop robust assays for measuring those components. They may propose to combine one or more previously identified signatures, for example, by integrating genomic data with gene expression measurements. They may continue to develop and/or modify analytical technologies and algorithms for data analysis that are required to meet the goals of the proposed projects.

Applicants must identify the resources required for advancing these molecular signatures toward clinical application, including access to Clinical Laboratory Improvement Amendments (CLIA)-certified clinical laboratories. Applicants are encouraged to establish collaborations with companies that have the potential to commercialize the successful clinical assay after the completion of the projects.

The projects proposed should address a well-defined clinical need so that, if the project is successful, molecular signatures or their derivatives can be considered in planning treatment for individual patients. Applicants at an earlier stage of development of comprehensive signatures for possible clinical use should consider PA-08-267, PA-09-158, PA-09-159, PA-08-133, PA-08-134, or PA-09-238.

Continued development and/or modification of analytical technologies and/or algorithms for data analysis and integration may be required to meet the goals of the proposed projects. However, these should be secondary objectives that are proposed only in order to meet the primary clinical/translational goals of the project. Applications proposing only profile discovery or technology development projects will not be considered responsive to this FOA.

Tissue Resources. The availability of tissue resources with appropriate clinical annotation is critical to the successful completion of the projects. Applicants will be required to present appropriate statistical designs for the proposed studies that will justify the numbers of specimens required. Experience has demonstrated that the heterogeneity of the patient populations requires the analysis of hundreds, not tens, of specimens in order to obtain statistically significant results. Applicants must have established collaborations to ensure availability of the clinical materials required. Applicants may propose to obtain tissues from a previous collection or prospectively, as long as the work can be accomplished in the period of the grant award. Demonstrated access to the requisite tissues will be critical to the success of the application. It is recognized that tissue needs may change as new data are generated during the projects. NCI staff members will work with investigators to help identify tissue specimens to meet unanticipated needs.

Specific Research Requirements for SPECS II

All applications submitted in response to this FOA are encouraged to conform to the research objectives and requirements of this FOA. Thus, every SPECS II application should have the following attributes:

• a single, well-developed research project that uses multi-analyte molecular signatures (as defined above) to overcome a major barrier and address a significant clinical question or need in cancer diagnosis and treatment;
• an appropriate multi-disciplinary team capable of designing and conducting exceptional translational research
• a plan for interactions with other components of the SPECS partnership.

Multidisciplinary Projects. The applications must establish the collaborations necessary to bring together all of the expertise needed for the project. Project teams should include committed individuals with expertise in analytical technologies, cancer biology, oncology, pathology, clinical cancer research, assay development, biostatistics, and bioinformatics. Availability of qualified experts in biostatistics and bioinformatics presents a particularly difficult challenge. Applicants must request sufficient resources to ensure that they will be able to collect, manage, and analyze the data generated. This requirement includes obtaining, managing and controlling the quality of the clinical data needed for specimen annotation. It is anticipated that investigators conducting the funded projects will cooperate to more effectively address the issues of data management and analysis.

Public Release of Data. Sharing of the data between projects where appropriate and public release of data after publication will be vital in achieving the goals for this initiative. All data should be shared through the caBIG website using the tools developed for SPECS, TARGET, The Cancer Genome Atlas (TCGA), REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT), and other NCI programs or projects, when possible, and through other publicly available websites.

Governance of the SPECS II Program. Although each applicant will propose an independent project, all applicants are expected to face many of the same challenges and would benefit from the experiences of and interactions with the other funded investigators. Therefore, the funded investigators will be asked to form a network Steering Committee made up of two investigators from each funded project and appropriate NCI staff members. The Steering Committee will focus on common problems and issues, especially issues of data management, analysis, and integration. An external Expert Consultant Panel consisting of experts in disciplines such as comprehensive molecular analysis, clinical cancer research, clinical assay development, bioinformatics, and biostatistics will also be established, to be recruited and supported by NCI. This panel will assist the Steering Committee develop strategies to effectively address issues and problems that arise during the conduct of the projects.

Confirmation, Evaluation, and Validation of Molecular Signatures in Clinical Trials. The confirmation and evaluation of clinically useful multi-analyte molecular signatures are the primary goals of this initiative. Further validation of the signatures in a clinical trial setting may be needed before signatures are recommended for integration into clinical practice. Experience with the original SPECS Program raises the expectation that some of the projects may be ready to move signatures into clinical trials as early as the midpoint of the project period. The Steering Committee, with input from NCI staff and the Expert Consultant Panel, will help identify and prioritize signatures ready for validation. It is anticipated that these projects will partner with other clinical resources and clinical trials activities supported by NCI including: the clinical cooperative groups; the Program for the Assessment of Clinical Cancer Tests (PACCT); the NCI-supported Specialized Programs of Research Excellence (SPOREs) and the NCI-designated Cancer Centers to carry out the proposed trials.

Clinical Assay Development Center. It is anticipated that the projects funded by this initiative will be well positioned to take advantage of the resources available through the Clinical Assay Development Center (CADC) and Network (CADN) established at NCI. The CADC and CADN will provide expertise in clinical assay development and optimization. They will have CLIA laboratory facilities and expertise in the development of Standard Operating Procedures and assay documentation. The CADC and CADN can significantly accelerate the development of credentialed clinical assays as the projects funded by this initiative move toward clinical application.

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 U01 award mechanism.

The applicant will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses Just-in-Time information concepts. It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html).

This is 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

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 IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds.

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:

• 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;
• Regional Organizations;
• Non-domestic (non-U.S.) Entities (Foreign Organizations); and
• Eligible Agencies of the Federal Government.

1.B. Eligible Individuals

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

More than one PD/PI (i.e., 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 and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH electronic Research Administration (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 grant 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. When considering the multiple PD/PI option, 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 may submit more than one application, provided that each application is scientifically distinct.

Resubmissions. Applicants may submit a resubmission application, but such application must include an Introduction addressing the previous peer review critique (Summary Statement).

Beginning with applications intended for the January 25, 2009 official submission due date, all original new applications (i.e., never submitted) and renewal applications are permitted only a single amendment (A1). See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-003.html and NOT-OD-09-016. Original new and renewal applications that were submitted prior to January 25, 2009 are permitted two amendments (A1 and A2). For these grandfathered applications, NIH expects that any A2 will be submitted no later than January 7, 2011, and NIH will not accept A2 applications after that date.

Renewals. Renewal applications are not permitted in response to this FOA.

Section IV. Application and Submission Information

1. Address to Request Application Information

The current 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: [email protected].

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

2. Content and Form of Application Submission

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

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

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

Applications from foreign organizations must:

• Request budgets in U.S. dollars.
• Contain detailed budgets. See NOT-OD-06-096.

In addition, for applications from foreign organizations:

• Charge back of customs and import fees is not allowed.
• Every effort should be made to comply with the format specifications, which are based upon a standard U.S. paper size of 8.5 x 11 within each PDF.
• Funds for up to 8% Facilities and administrative (F&A) costs (excluding equipment) may be requested. See NOT-OD-01-028, March 29, 2001.
• Organizations must comply with Federal/NIH policies on human subjects, animals, and biohazards.
• Organizations must comply with Federal/NIH biosafety and biosecurity regulations. See Section VI.2., Administrative and National Policy Requirements.

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

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PD/PIs are proposed, 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 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, the section of the Research Plan entitled Multiple PD/PI Leadership Plan , 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

See Section IV.3.A. for details.

3.A. Submission, Review, and Anticipated Start Dates
Letters of Intent Receipt Dates: May 15, 2010, May 15, 2011, May 15, 2012
Application Receipt Dates: June 15, 2010, June 15, 2011, June 15, 2012
AIDS Application Receipt Dates: Not Applicable
Peer Review Dates: November 2010, November 2011, November 2012
Council Review Dates: January 2011, January 2012, January 2013
Earliest Anticipated Start Dates: April 2011, April 2012, April 2013

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 NIH institute or center (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:

Tracy Lively, Ph.D.
Division of Cancer Treatment and Diagnosis (DCTD)
National Cancer Institute (NCI)
6130 Executive Boulevard, EPN Room 6035A
Bethesda, MD 20892-7420
Telephone: (301) 496-1591
Fax: (301) 402-7819
E-mail: [email protected]

3.B. Submitting an Application to the NIH

Applications must be prepared using the research grant application 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 materials 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: [email protected]

3.C. Application Processing

Applications must be received on or before the application receipt/ date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review.

Upon receipt applications will be evaluated for completeness by CSR. Incomplete 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 merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. However, the NIH will accept a resubmission application, but such application must include an Introduction addressing the critique from the previous review.

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.

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

Participation of SPECS II Awardees in the Activities of the SPECS Consortium

In order to ensure maximum progress in the projects supported by this initiative, the awardee investigators will be asked to work together on issues common to all the funded projects. Although each applicant will propose an independent project, all funded investigators are expected to face many of the same challenges and will benefit from the experiences of and interactions with the other awardees. The interactions of the funded groups will be overseen by a Steering Committee made up of two investigators, including the PI and one additional investigator from each funded project, and appropriate NCI staff members. A Steering Committee organizing meeting will be held shortly after funding is initiated. The Steering Committee will focus on common problems and issues, for example, challenges of data management and analysis. Applicants should state in their applications their commitment to participating on the Steering Committee and in interactions among the funded groups.

An annual meeting of all funded investigators will be held to share progress and research insights that may benefit all the projects. The Steering Committee will be responsible for organizing this annual meeting. The Steering Committee will also organize one or more other focused meetings each year to address arising issues or to take advantage of special scientific opportunities. Applicants should request travel funds in their budgets for key personnel to attend two meetings per year.

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

PHS398 Research Plan Component Sections

All application instructions outlined in the PHS 398 Application Guide are to be followed, with the following additional requirements:

• Introduction (required for a resubmission or revision application) is limited to 1 page.
• Specific Aims is limited to 1 page.
• Research Strategy, including tables, graphs, figures, diagrams, and charts is limited to 12 pages. See Table of Page Limits.

Budget Component

This FOA uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html).

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.

Specific Instructions for Applications Requesting $500,000 (direct costs) or More per Year

Applicants requesting $500,000 or more in direct costs for any year (excluding consortium F&A costs) must carry out the following steps:

1) Contact the IC program staff at least 6 weeks before submitting the application, i.e., as plans are being developed for the study;

2) Obtain agreement from the IC staff that the IC will accept the application for consideration for award; and,

3) Include a cover letter with the application that identifies the staff member and IC who agreed to accept assignment of the application.

This policy applies to all new, renewal, revision, or resubmission applications. See NOT-OD-02-004, October 16, 2001.

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. 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: Investigators are expected to include a description of how final research data will be shared, or explain why data-sharing is not possible. The plan should address the sharing of unique research resources and data generated through the grant and how intellectual property will be managed so that the goals of the initiative can be met, including the goal of making the research results available to the scientific community. See NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131) and NIH Sharing Policies and Related Guidance on NIH-Funded Research Resources (http://sharing.nih.gov) for additional information. To the extent that this FOA anticipates multi-disciplinary teams potentially involving multiple institutions, it is expected that the plan address the data and intellectual property sharing among collaborators so that the goals of the program can be achieved. For guidance, applicants may wish to review NIH sharing policies at http://sharing,nih.gov (e.g., Developing Sponsored Research Agreements at https://s-edison.info.nih.gov/iEdison/sponsored.jsp) and NIH invention policies at http://inventions.nih.gov. In addressing these issues, applicant should work with their own institution s technology transfer office. Examples of possible IP sharing approaches that applicants and their institutions may choose to explore can be found at http://ttc.nci.nih.gov/intellectualproperty/. Further, 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/.

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.

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

Review 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:

• 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 an impact/priority score.
• Receive a written critique.
• Receive a second level of review by National Cancer Advisory Board.

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

Overall Impact

Reviewers will provide an overall impact/priority 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 scored review criteria, and additional review criteria (as applicable for the project proposed).

Scored 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? Does the proposed project build upon previously identified molecular profiles? Does it address a well-defined clinical question or need? If successful, how will it improve clinical care for cancer patients? Is this project ready to bridge the gap between discovery and clinical implementation?

Investigator(s). Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, 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? Does the proposed research team provide appropriately balanced leadership and expertise in oncology, analytical technologies, pathology, cancer biology, clinical cancer research, assay development, bioinformatics, and biostatistics? Does the research team have a track record of prior successful collaborative research? If collaborating institutions involve industry or small business entities, how will this inclusion enhance the applicants research and their plans for technology translation/dissemination? For applications involving multiple PDs/PIs, are their designated roles and responsibilities well defined, adequate, and appropriate for achieving the goals of the proposed SPECS II project? How appropriate is the leadership structure in terms of coordination of efforts of multiple institutions participating in a given SPECS II 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? Has the investigator documented access to the patients and/or specimens with appropriate annotation in sufficient quantities to satisfy the statistical design and other goals of the proposed studies?

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? Are consortium/contractual arrangements, if any, appropriate and adequately described?

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. For additional information, see http://grants.nih.gov/grants/olaw/VASchecklist.pdf.

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.

Resubmission Applications. When reviewing a Resubmission application (formerly called an amended application), the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewal Applications. Renewal applications are not permitted in response to this FOA.

Revision Applications. When reviewing a Revision application (formerly called a competing supplement application), the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Additional Review Considerations

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

Select Agents 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).

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

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

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.

Selection Process

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

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

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 NIH eRA Commons.

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

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

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.

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 U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (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.

2.A.1. Project Director/Principal Investigator (PD/PI) Rights and Responsibilities

The PD(s)/PI(s) will have the primary responsibility for defining objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of studies conducted under this program. The PD(s)/PI(s) assume(s) responsibility and accountability to the applicant organization officials and to the NCI for the performance and proper conduct of the research supported by the U01 in accordance with these terms and conditions of the award.

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.

Specific rights and responsibilities will include the following:

• The PD(s)/PI(s) for each U01 award will have the primary authority and responsibility for the project as a whole, including defining the research objectives, conducting specific studies, analysis and interpretation of research data, and preparation of publications;
• Representatives of each U01 award will be expected to work with the NCI Project Scientist on the coordination of research program activities -- These actions may involve (but will not be limited to) the participation in the appropriate meetings and/or working groups, and/or teleconferences as needed;
• A PD/PI of each U01 project and at least one additional PD/PI or key personnel member will participate in the annual consortium meeting;
• In addition to providing standard annual progress reports (see Section VI.3. Reporting), each U01 awardee will be responsible for providing other relevant information to the NCI Project Scientist, and will coordinate and cooperate with NCI staff and other members of the Program; and
• Each U01 awardee 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.

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 designated NCI Program Director acting as a Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. The NCI Project Scientist will not attend peer review meetings of applications. If such participation is essential, these individuals will seek NCI waiver according to the NCI procedures for management of conflict of interest.

The main NCI responsibilities include the following activities. Specifically, the NCI Project Scientists will:

• Coordinate and facilitate the interactions among the U01 awardees under this initiative;
• Serve as liaison between the research awardees and NCI staff members and investigators involved in the program, facilitating interactions and scientific integration between the U01 awardees;
• Promote and help coordinate collaborative research efforts that involve interactions with other NCI-supported projects, programs, and centers;
• Participate in program meetings;
• Review all major transitional changes that the awardees might propose (e.g., a change in partnering institution) and advise on their appropriateness prior to implementation to assure consistency with the goals of this FOA;
• Provide technical assistance and advice to the awardees as appropriate;
• Assist in the interaction between the U01 research awardees and investigators at other institutions, as appropriate for the program;
• Assist in avoiding unwarranted duplication of effort with other NIH efforts;
• Monitor institutional commitments and resources to the awardees;
• Suggest reprogramming efforts, including options to modify projects/programs when certain objectives of this FOA are not met -- Specifically, the NCI Project Scientist may recommend withholding of support, suspension, or termination of a U01 award for lack of adherence to required policies and/or procedures;
• Develop working groups and trans-project efforts as needed; and
• Organize and conduct regular meetings to share progress either by teleconference, videoconference, or face-to-face, as needed between the awardees.

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) and may be the same person as Project Scientist. In that case, the individual involved will not attend peer review meetings of applications, or will seek NCI waiver.

2. A.3. Collaborative Responsibilities

The NCI Project Scientist and the PD(s)/PI(s) of the U01 awards funded under the research initiative will be jointly responsible for the coordination of intra-program activities and the scientific integration of individual projects.

The NCI Project Scientist and PDs/PIs will organize and attend an annual meeting of the awardees of this initiative.

The Steering Committee, composed of the PIs/PDs, a second key member of each funded project, and the NCI Project Scientist, will be responsible for developing strategies to address issues common to all of the projects funded by this initiative. Investigators agree to follow common policies and procedures developed by the Steering Committee. The Steering Committee will pay special attention to issues of data integration, management, analysis, and public release and may establish subcommittees as necessary. The participants will select a chairperson for the Steering Committee. An NCI Program staff member cannot serve as chairperson.

An Expert Consultant Panel will be appointed by the NCI with concurrence of the Steering Committee. The Panel will consist of no more than six members with expertise in comprehensive molecular technologies, oncology, statistics, data analysis, and bioinformatics. The Panel will advise the NCI staff and the Steering Committee and assist in the development of strategies to meet consortium goals. Members of the Expert Consultant Panel will attend consortium meetings and will advise the Steering Committee on an ad hoc basis as needed.

Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

2.A.4. Dispute Resolution

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. A Dispute Resolution 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 dispute resolution procedure does not alter the awardee's rights in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

When multiple years are involved, 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 (program); peer review; and financial or grants management issues:

1. Scientific/Research Contact(s):

Tracy Lively, Ph.D.
Division of Cancer Treatment and Diagnosis (DCTD)
National Cancer Institute (NCI)
6130 Executive Boulevard, EPN Room 6035A
Bethesda, MD 20892-7420
Telephone: (301) 496-1591
Fax: (301) 402-7819
E-mail: [email protected]

James V. Tricoli, Ph.D.
Division of Cancer Treatment and Diagnosis (DCTD)
National Cancer Institute (NCI)
6130 Executive Boulevard, EPN Room 6035A
Bethesda, MD 20892-7420
Telephone: (301) 402-4185
Fax: (301) 402-7819
E-mail: [email protected]

2. Peer Review Contact(s):

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: [email protected]

3. Financial/Grants Management Contact(s):

Shane Woodward
Acting Branch Chief
Grants Management Portfolio Branch B
Office of Grants Administration
National Cancer Institute
6120 Executive Plaza South, Suite 243
Bethesda, MD 20852
Telephone: 301-496-8791
Fax: 301-496-8601
Email: [email protected]

Section VIII. Other Information

Required Federal Citations

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

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

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

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing). Investigators should seek guidance from their institutions, on issues related to institutional policies and local institutional review board (IRB) rules, as well as local, State and Federal laws and regulations, including the Privacy Rule.

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/.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh-Dole Act (see the NIH Grants Policy Statement. Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

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.

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

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

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

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

Human Embryonic Stem Cells (hESC):
Criteria for Federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-116.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.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy, investigators funded by the NIH must submit or have submitted for them to the National Library of Medicine’s PubMed Central (see http://www.pubmedcentral.nih.gov/), an electronic version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no later than 12 months after the official date of publication. The NIH Public Access Policy is available at (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html). 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 (HHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the HHS Office for Civil Rights (OCR).

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

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

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

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

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

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