Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Cancer Institute (NCI)
Funding Opportunity Title	Strategic Partnering to Evaluate Cancer Signatures [SPECS II] (U01)
Activity Code	U01 Research Project Cooperative Agreements
Announcement Type	Reissue of PAR-10-126
Related Notices	None
Funding Opportunity Announcement (FOA) Number	PAR-11-151
Companion FOA	NoneNone
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.394, 93.395
FOA 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.

Posted Date	March 14, 2011
Open Date (Earliest Submission Date)	May 15, 2011
Letter of Intent Due Date	May 15, 2011, May 15, 2012
Application Due Date(s)	June 15, 2011, June 15, 2012, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	November 2011, November 2012
Advisory Council Review	January 2012, January 2013
Earliest Start Date(s)	April 2012, April 2013
Expiration Date	June 16, 2012
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

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 this development, however, have been identified by the PACCT Strategy Group. These barriers 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 (http://www.cancerdiagnosis.nci.nih.gov/scientificPrograms/specs.htm). 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 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. These accomplishments reflect both the individual research projects as well as participation in the childhood cancer research program called the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) Program (http://target.cancer.gov/). 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.

Applicants are 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).

Research topics of interest 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. Proposed projects are expected to focus on the development of 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 for the goals of the proposed projects. However, these developmental activities 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. Steering Committee will also establish an external Expert Consultant Panel consisting of experts in disciplines such as comprehensive molecular analysis, clinical cancer research, clinical assay development, bioinformatics, and biostatistics. 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.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed	New Resubmission The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications.
Award Budget	Requested application budgets must not exceed $680,000 per year (direct costs) in any year of the award. Facilities and Administration (F & A) costs on any subcontracts are excluded from the direct costs that count towards the cap.
Award Project Period	The total project period for an application submitted in response to this funding opportunity may not exceed 5 years.

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.

Higher Education Institutions:

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions

Nonprofits Other Than 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)

For profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)

Foreign (non-U.S.) components on applications submitted by U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• Grants.gov
• eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

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

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

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

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

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

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, MSC 7420
Bethesda, MD 20892-7420 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-1591
Fax: (301) 402-7819
E-mail: livelyt@mail.nih.gov

The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for application submission. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Note: All applications submitted in response to this FOA must use detailed, non-modular budget format.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

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 awardees 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".

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modifications:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix

Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

Applicants are responsible for viewing their application in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

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 only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD/PIs must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the Central Contractor Registration (CCR). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by the NCI, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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 review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific 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, 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?

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?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, 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. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

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. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

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 on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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.

Resubmissions

For Resubmissions, 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.

Renewals

Not Applicable

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider 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.

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.

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

Applications will be evaluated for scientific and technical merit by (an) appropriate panel of experts convened by the NCI , using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May 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 overall impact/priority score.
• Will receive a written critique.

Applications will be assigned to the NCI.. Applications will compete for available funds with all other recommended applications . Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory Board. The following will be considered in making funding decisions:

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

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.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. 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.

Any application awarded in response to this FOA will be subject to the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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

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 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.

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) assumes(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..

Specific PD/PI 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 and participate in the activities of the Steering Committee for this initiative;
• 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 senior/key personnel member will participate in the Steering Committee meetings and the annual consortium investigators 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
• 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.

NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

A designated NCI Program Director acting as a Project Scientist will have the following responsibilities:

• Coordinating and facilitating the interactions among the U01 awardees under this initiative;
• Serving 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;
• Promoting collaborative research efforts that involve interactions with other NIH-supported projects, programs, and centers and assisting with the coordination of these efforts;
• Participating in program meetings;
• Reviewing all major transitional changes that the awardees might propose (e.g., a change in partnering institution) and advising on their appropriateness prior to implementation to assure consistency with the goals of this FOA;
• Providing technical assistance and advice to the awardees as appropriate;
• Assisting in the interaction between the U01 research awardees and investigators at other institutions, as appropriate for the program;
• Assisting in avoiding unwarranted duplication of effort with other NIH efforts;
• Monitoring institutional commitments and resources to the awardees;
• Suggesting reprogramming efforts, including options to modify projects/programs when certain objectives of this FOA are not met;
• Recommending withholding of support, suspension, or termination of a U01 award for lack of progress and/or adherence to required policies/procedures;
• Assisting the awardees with the development of working groups and trans-project efforts as needed; and
• Organizing and conducting regular meetings to share progress either by teleconference, videoconference, or face-to-face, as needed between the awardees.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. A Program Official may also have substantial programmatic involvement (as Project Scientist) and may be the same person as the Project Scientist. The substantially involved NCI staff members will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications. If such participation is deemed essential, these individuals will seek NCI waivers according to the NCI procedures for management of conflict of interest.

Areas of Joint Responsibility include:

The NCI Project Scientist and the PD(s)/PI(s) of the U01 awards funded under this FOA will be jointly responsible for the coordination of intra-program activities and the scientific integration of individual projects. These responsibilities include joint participation in the Steering Committee.

The Steering Committee will be composed of two representatives of each awardee (two PDs/PIs, or a PD/PI and a second key member) and the NCI Project Scientist. Each full member will have one vote. The members of the Steering Committee will select a chairperson (who cannot be an NCI Program staff member).

The Steering Committee will be responsible for developing strategies to address issues common to all of the projects funded under this initiative. The Steering Committee will pay special attention to issues of data integration, management, analysis, and public release and may establish subcommittees as necessary.

Awardees under this FOA will be required to accept and implement policies approved by the Steering Committee to the extent consistent with the applicable grant regulations.

The NCI Program staff members and the Steering Committee will organize an annual meeting of the awardees of this initiative.

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 Dispute Resolution. 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 right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

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.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Tracy Lively, Ph.D.
Division of Cancer Treatment and Diagnosis (DCTD)
National Cancer Institute (NCI)
6130 Executive Boulevard, EPN Room 6035A, MSC 7420
Bethesda, MD 20892-7420 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-1591
Fax: (301) 402-7819
E-mail: livelyt@mail.nih.gov

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: tricolij@mail.nih.gov

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..

Shane Woodward
Acting Branch Chief
Grants Management Portfolio Branch B
Office of Grants Administration
National Cancer Institute
6120 Executive Plaza South, Suite 243, MSC 7150
Bethesda, MD 20892-7150 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for non-USPS delivery)Telephone: 301-496-8791
Fax: 301-496-8601
Email: Woodwars@mail.nih.gov

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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.