Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (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

This Funding Opportunity Announcement (FOA) invites grant applications for support of the core functions of Cancer Epidemiology Cohorts (CECs), as well as methodological research. This FOA is intended to support innovative approaches to maintain or enhance the infrastructure of an existing CEC or the establishment of a new CEC. Through this FOA, the NCI will also support core functions for CECs currently funded through other grant mechanisms by the Epidemiology and Genomics Research Program (EGRP) and other components of the Division of Cancer Control and Population Sciences (DCCPS) at NCI.

Classic CECs are large observational population studies in which groups of people with a set of characteristics or exposures are followed systematically and prospectively for the incidence of new cancers, cancer mortality, and/or cancer-related outcomes. This definition includes large cohorts of cancer patients/survivors involving longitudinal assessment of responses to therapies and short- and long-term health outcomes occurring after diagnosis. CEC-based studies have helped advance our understanding of the complex etiology of cancer and provided fundamental insights into key environmental, lifestyle, and genetic determinants of this disease. Findings from CECs may also serve as a basis for risk prediction models, cancer control trials, intervention strategies, and/or the design and testing of many preventive and therapeutic interventions. Large biorepositories established by CECs already support genomic and epigenetic studies, and are beginning to support proteomic and metabolomic studies.

High-quality, population-based cohort studies can provide a foundational framework for epidemiology across the cancer continuum from etiology to survivorship. CECs have enabled large-scale genome-wide association studies (GWAS) and replication of prior GWAS findings. The application of next-generation sequencing technologies within this context is contributing to the identification of putative cancer susceptibility loci and may potentially lead to the identification of genes associated with prognosis and survival for a variety of cancers. NCI recognizes that CECs are valuable resources that benefit the entire cancer research community. Successful cohorts of the 21st century will need to be maximally suited to participate in a large, worldwide network of cohorts to achieve the statistical power needed to address increasingly complex scientific questions, and accrue large and diverse population samples. Collaboration in such a network would be enormously facilitated by CEC involvement in NCI efforts toward cross-cohorts data harmonization.

Types of Qualifying Cancer Cohorts. Support through this FOA is envisioned for three types of CECs:

1) CECs with at least 10,000 study participants that are capable of supporting studies to examine the effects of multiple exposures and study participants characteristics on the risk of multiple types of cancers and cancer mortality; and

2) Cohorts of cancer patients/survivors of at least 5,000 participants (across multiple cancer sites) or at least 2,000 participants (diagnosed with the same or narrowly related cancer sites) to support research addressing determinants of cancer progression, recurrence, mortality, incidence, and other cancer/health-related outcomes.

Cohorts established to assess the role of exposures in the workplace on risk of cancer (i.e., occupational cohorts ) may be appropriate for this FOA, but only if they were established to examine a broad range of exposures potentially experienced by the general public and/or genomic factors affecting cancer risk or outcomes after cancer diagnosis. Cancer surveillance activities and development and maintenance of registries of persons with particular characteristics that do not address identification of factors affecting risk are not appropriate for this FOA.

This FOA must be used for all requests for support to continue and enhance existing CECs or to establish new CECs. The activities to be supported through this FOA include the establishment, maintenance, or upgrade of CECs core functions. Methodological research to validate or evaluate new or existing approaches to core infrastructure functions (for example, validation of novel approaches to exposures assessment) is also appropriate.

Applicants to this FOA are expected to focus on activities that will:

• Enable efficient planning and operation of cohorts; maximize their potential to respond to future scientific needs;
• Enable the CECs to address cutting-edge research questions related to cancer susceptibility in human populations; and
• Facilitate scientific collaborations across cohorts

Research projects relying on the CECs infrastructure are NOT appropriate for this FOA and should seek support through appropriate research project mechanisms such as investigator-initiated R01 and P01 grants.

Specific core functions that can be supported for the existing or newly proposed cohorts include, but are not limited to:

• Ongoing or new accrual of the target population, and enrollment of special and/or under-represented populations in the sampling frame;
• Follow-up (active and passive) of enrolled participants;
• Systematic, high-throughput assessment of genetic or other biological markers when required to interpret new research findings, or when these markers are not already available on all relevant cohort study subjects (e.g., tumor hormone receptor status);
• Validation, quality control, standardization, harmonization, and/or calibration of data across cohorts;
• Biospecimen collection and management, with emphasis on blood and tissue collection;
• Development of bioinformatics and big data approaches for managing, storing, integrating, and sharing information from multiple levels (from ecologic to molecular);
• Data management and administrative and communication tasks; and
• Utilization of modern approaches, such as mobile web-based technologies for data collection and communication with participants is strongly encouraged.

Although not required for this FOA, proposed Cancer Survivor Cohorts would likely accrue the following information:

• Patient demographics (e.g., age, race/ethnicity, sex, education, family and prior cancer history);
• Patient clinical characteristics and basic diagnostic information (e.g., functional status);
• Co-morbidities (e.g., cardiovascular disease, diabetes, chronic obstructive pulmonary disease);
• Lifestyle (e.g., diet, physical activity, body mass index, smoking, alcohol use), preferably measured before and after cancer diagnosis;
• Disease characteristics (e.g., histology, size, stage, grade, tumor biomarkers);
• Detailed information on the type and dose of treatment received to include initial and adjuvant therapies (e.g., surgery, radiation, chemotherapy, hormonal therapy, and bone marrow/stem cell transplant);
• Clinical endpoints (e.g., treatment response and any treatment-related toxicities, progression/recurrence, overall and cause-specific survival, quality of life, second neoplasms);

Tumor specimens and other biospecimens (e.g., germline DNA, normal tissue) collected at diagnosis (i.e., pre-therapy) and after diagnosis.

Consolidation of CEC Support. Currently, core functions of a CEC may be supported by multiple research project grants, but this fragmented support is not optimal (e.g., individual research project grants may have only partially overlapping funding periods). This FOA allows for the fragmented infrastructure components of a CEC to be consolidated under a single cooperative agreement (U01) award. The transition to the consolidated infrastructure support may be initiated, for example, when a grant(s) that contains core infrastructure components becomes eligible for renewal. If the application is selected for funding, the overlap with other grants will be administratively adjusted.

Informatics. Awardees will be required to provide regularly updated descriptive and meta-data to NCI, including cohort characteristics, study protocols, basic counts of study participants, biospecimen availability, and study variable definitions. Investigators will be expected to evaluate and document compliance with NCI s Best Practices for Biospecimen Resources (http://biospecimens.cancer.gov/bestpractices) for collection, processing, and storage of biospecimens. NCI will compile these data across cohorts and make the information available online to assist the research community in identifying potential cohorts to address specific research questions or evaluate the potential for cross-cohort studies. Awardees will be required to contribute to a cross-CEC data harmonization with NCI staff and other awardees through participation in working groups.

Annual Meeting. Awardees under this FOA will be required to participate in an annual investigators meeting of this Cohort Network, which may be concurrent with the NCI Cohort Consortium annual meeting, to foster interaction with investigators involved in the conduct of diverse cohorts, or may be hosted on a rotating basis at the participating PD/PIs' Institutions. Application for membership in the NCI Cohort Consortium is also strongly encouraged (see http://epi.grants.cancer.gov/Consortia/cohort.html).

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
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

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
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) 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 SF424 (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.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

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, including Supplemental Grant Application Instructions 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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 activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Joanne Elena, Ph.D., M.P.H.
Epidemiology and Genomics Research Program
Division of Cancer Control and Population Sciences
National Cancer Institute
Telephone: 240-276-6818
Email: joanne.elena@nih.gov

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

• For this specific FOA, the Research Strategy section is limited to 30 pages with the following suggested page limits for each section:
• Program (Cohort) Overview - 12 pages
• Infrastructure Design and Research Program - 12 pages
• Leadership and Administrative Core - 6 pages

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

Facilities and Other Resources: Each application must have a defined space for administrative activities and administrative personnel that will serve as a focus for data management, quality control, and communication.

All instructions in the SF424 (R&R) Application Guide must be followed.

Biographical Sketch: The experience with CECs for proposed PD(s)/PI(s) must be described, specifically documenting their respective abilities to organize and manage a CEC and related activities.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

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

Specific Aims: Provide Specific Aims for the enhancement and/or maintenance of the cohort core infrastructure, as well as methodological research proposed in the application.

Research Strategy: The Research Strategy must consist of the following sections:

Cohort Overview

• Background and Experience. Describe the group’s history and experience in designing and implementing CECs.
• Overall description and summary purpose of proposed cohort.
• Progress (existing cohorts only). Include a progress report describing the CEC’s accomplishments relative to both infrastructure and supported research, including clinical and public health impact of research arising from the cohort. Include a summary of accrual, data and biospecimen collection, and follow-up over the past project period. If a data sharing plan was accepted and made a term and condition of award, include a report describing compliance with the final data sharing plan.

Infrastructure Design and Research Program

• Cohort Infrastructure. The application must delineate its catchment area and/or sampling frame. A description of the study population in the application’s catchment area, with a breakdown by percentage of gender and racial/ethnic subpopulations, using categories described in https://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-053.html, should be provided. The CEC’s design and projected or known composition must be described in detail. Approaches and methods proposed for recruitment and follow-up of patients, collection and management of biospecimens, high-throughput assays, data management, quality control, and internal data sharing policies must be described.
• Core Infrastructure Activities. Describe the planned activities related to the core infrastructure functions.
• Organizational Structure. The application must describe the current and/or planned organizational structure under which the CEC proposes to operate. An organizational chart showing how the group will function must also be included. The availability of cancer registries must be described. Applicants, whose applications are considered for funding, will have to provide fully executed consortium agreements as a Just-in-Time requirement.
• Methodologic Research. The application should describe the group’s plans for methodologic research aimed at developing, testing, and validating new methods and approaches to improve the proposed cohort infrastructure.
• Broad Research Agenda. The application should describe the scientific rationale underpinning the need for the cohort and a broad research agenda the cohort will be designed to support in the short, medium, and long range.

Leadership and Administrative Core

The use of the multiple PD/PI option is encouraged. Proposed duties of all proposed essential support personnel should be described.

Letters of Support: A statement of commitment from each participating institution or organization and/or documentation of consortium arrangements must be provided. Also include Letters of Intent to establish a Consortium.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan that is compliant with NIH data sharing policies.

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.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to 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. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

Applicants are responsible for viewing their application before the due date 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.

For renewal applications, the direct cost budget request for the first year cannot generally exceed an increase of 10% over the direct cost budget awarded for the last year of the prior project period (i.e., the last Type 5 award). This dollar cap for the direct cost increase is exclusive of any consortium/sub-contractual component of Facilities and Administrative (F&A) costs that may appear as direct cost in the budget of the applicant organization. For more information please see, https://grants.nih.gov/grants/guide/notice-files/NOT-CA-08-026.html

Applications must be submitted electronically following the instructions described in the SF424 (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. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(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. See Section III of this FOA for information on registration requirements.

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 System for Award Management. 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 and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Applicants are required to follow our Post Submission Application Materials policy.

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 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.

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

In addition, specific to this FOA: How will the implementation of the proposed core functions improve the capability to address the cohort scientific agenda? Will the proposed cohort have the capacity to support multi-level analyses (from the individual to the environmental/social structure and health systems levels) and integrative analyses (pooled and meta-analyses in cooperation with other cohorts)?

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

In addition, specific to this FOA: Is the proposed CEC infrastructure capable of supporting a cutting-edge, broad research agenda? Is the investigator proposing to use innovative technologies and approaches in the establishment and /or maintenance of the proposed cohort, in particular, in fostering enrollment and participation of understudied populations, and the collection of exposure and biomarker data?

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 human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

In addition, specific to this FOA: Are there appropriate plans for the rigorous management and quality control of data and biospecimens collected by the CEC? Are the CEC objectives described likely to be completed during the requested period? Are the administrative and communication structures in terms of efficiently supporting the CEC s activities adequate? For the continuing CECs, are the follow-up rates and/or response rates (especially the first round of follow-up) adequate? Are the length of follow-up and age characteristics of the cohort appropriate? Are the types and number of outcome variables tracked appropriate for the intended research scope?

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 score, but will not give separate scores for these items.

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 Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

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.

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.

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.

For Renewals, the committee will consider the progress made in the last funding period.

For Revisions, 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.

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 score.

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.

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).

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) Genomic Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

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 Scientific Review Group(s) convened by NCI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group 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 score.
• Will receive a written critique.

Applications will be assigned on the basis of established NIH referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. 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’s 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 terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this 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;
• Defining the research plan and goals;
• Overseeing the analyses and interpretation of studies conducted under this program as well as publication of their results;
• Overseeing/performing other scientific activities of the plan;
• Monitoring the completion of the supported activities and taking corrective actions if needed;
• Participating in the activities of the Program Steering Committee;
• Accepting and implementing the policies approved by the Program Steering Committee to the extent consistent with applicable grant regulations;
• Cooperating with NCI programmatic, technical, and administrative staff; and
• Administratively managing the U01 award.

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 award in accordance with these terms and conditions of the award.

Specific rights and responsibilities of awardees will include the following: Awardees will be expected to evaluate and document compliance with NCI’s Best Practices for Biospecimen Resources, for collection, processing, and storage of future and past biospecimens (http://biospecimens.cancer.gov/bestpractices). Awardees will be required to explore, with NCI staff and other awardees of this FOA, the feasibility of pooling exposure data across cohorts. Awardees will be required to provide descriptive data and metadata on cohort characteristics through a pooled NCI database. Awardees are encouraged to register the cohort through ClinicalTrials.gov (http://clinicaltrials.gov). 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 Official(s), acting as a Project Scientist(s), will have the following responsibilities:

• Participating in the activities of the Program Steering Committee;
• Facilitating collaborations between the awardees and other NCI-sponsored programs, investigators, or organizations that may contribute to the projects goals;
• 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;
• Assisting in the interaction between the U01 research awardees and investigators at other institutions, as appropriate for the program;
• Promoting collaborative research efforts that involve interactions with other NIH-supported projects, programs, and centers and helping with the coordination of such efforts;
• Facilitating harmonization of data, biospecimen resource optimization and systematic assessment of molecular markers;
• 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 ensure consistency with the goals of this FOA;
• Providing technical assistance and advice to the awardees as appropriate; and
• Organizing and conducting regular meetings to share progress either by teleconference, videoconference, or face-to-face, as needed between the awardees.

Additional NCI staff members may be designated to have substantial involvement. The substantially involved NCI staff members will not attend peer review meetings of renewal (competing continuation) and/or revision applications. If such participation is deemed essential, these individuals will seek NCI waivers according to the NCI procedures for management of conflict of interest.

In addition, a separate NCI Program Official will be responsible for normal program stewardship and will be named in the Notice of Award.

The NCI reserves the right to adjust funding, or withhold, suspend, or terminate the support to those awardee institutions that are unable to meet the performance requirements set forth in these Terms and Conditions of Award, or significantly change the level of performance.

Areas of Joint Responsibility

The Steering Committee will serve as the main governing board for the CEC Core Functions and Methodological Research FOA.

The Steering Committee will consist of the following voting members:

• Two representatives of each awardee (the contact PD/PI and a designated backup senior investigator), who will collectively have one vote; and
• Two NCI Project Scientists who will collectively have one vote for the NCI.

The appointed voting CEC members will be required to attend all the CEC Steering Committee meetings and teleconferences or to appoint a substitute that will be fully briefed on the issues at hand. Additional non-voting members to serve in an advisory capacity may be added to the Steering Committee as needed by a decision of the existing voting committee members. Steering Committee may also form subcommittees as needed. The NCI Project Scientist may serve on such subcommittees as deemed appropriate. The Chair of the Steering Committee will be selected from the SC voting members.

The Steering Committee will meet one time per year in a face-to-face meeting. The Steering Committee chair will meet with NCI Project Scientists once a month by telephone conference.

The Steering Committee will have primary responsibility for:

• Overseeing the overall organization of the CEC Core Functions and Methodological Research initiative;
• Providing guidance on scientific and infrastructural issues pertinent to the funded cohorts;
• Coordinating integration of CEC Core Functions and Methodological Research awardees regarding common issues and projects;
• Providing guidance and overseeing and coordinating the activities of individual awardees towards cross-cohorts data harmonization;
• Contributing to the development of policies and processes pertinent to the CEC infrastructures; and
• Providing integration with the NCI Cohort Consortium on common issues and projects.

CEC Core Functions and Methodological Research awardees will be required to accept and implement the policies approved by the Steering Committee to the extent consistent with applicable grant regulations.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

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.

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: https://grants.nih.gov/support/index.html
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-945-7573
Email: GrantsInfo@nih.gov

Joanne Elena, Ph.D., M.P.H.
National Cancer Institute (NCI)
Telephone: 240-276-6818
Email: joanne.elena@nih.gov

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: ncirefof@dea.nci.nih.gov

Carol Perry
National Cancer Institute (NCI)
Telephone: 240-276-6282
Email: perryc@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.