Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from 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 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) solicits applications proposing research projects that use integrative systems-level approaches to address a defined gap in metastasis research. Such projects are expected to integrate with the NCI’s Metastasis Research Network (MetNet) and complement its ongoing research.

Proposed projects should emphasize one of the central themes defined in the MetNet FOA (RFA-CA-20-029) such as dormancy, early dissemination, cellular and/or physical microenvironment crosstalk, or mechanisms of responses by metastatic cells to therapies.

Consideration of a central theme within specific areas of research encouraged by this initiative includes, but are not limited to:

• Early dissemination and crosstalk as they apply to metastasis from the cancer of the lungs, prostate, pancreas, liver, kidney, bladder, or ovary;
• Metastasis to sites such as the bone, lungs, or rare sites;
• Metastatic processes such as the establishment of, maintenance of, or emergence from dormancy; and
• Mechanisms of metastasis in cancers with rising mortality rates and those with high incidence in diverse populations are highly encouraged.

Background

The MetNet. Launched in 2021, the MetNet consists of U54 Research Centers that support, using systems level approaches to elucidate and integrate a mechanistic understanding of the non-linear, dynamic processes in metastasis. Considering both chronological progression and biological scales, the overall goal of the MetNet is to advance our understanding of metastasis as a whole body, systems-level problem with the goal of developing a comprehensive and cohesive picture of the emergent processes involved. The MetNet is governed by the MetNet Steering Committee. The U01 Research Project awardees supported under this FOA will integrate into and be required to participate in all MetNet activities, including serving as Steering Committee members.

Complexity of Metastatic Dissemination. Our understanding of the mechanisms associated with metastasis is complicated by the fact that some genetically distinct cancer cells can disseminate early, and, for some, before progression to clinically defined invasive stages of primary cancer. Dissemination occurs in the context of a multitude of complex reciprocal interactions among the tumors and their soluble and physical microenvironments that can promote dynamic crosstalk between multiple organ systems creating a systemic disease. Despite increased understanding of many of the individual steps in metastasis, less is known about how each step is influenced by or influences distant tissues and the whole organism. Dissemination can occur non-linearly, via multiple concurrent, partially overlapping routes that require the acquisition of cell-autonomous and microenvironment-mediated metastasis-promoting phenotypes. Because the molecular requirements are distinct for growth in different organs and environments, defining such phenotypes is challenging. However, the use of integrative approaches that incorporate the host micro- and macroenvironments, immune-mediated events, and crosstalk among the primary tumor, pre-metastatic, and metastatic sites can aid in shedding light on the complexity and dynamic nature of metastasis.

Understanding the Spectrum of the Metastatic Process and Dormancy. In general, metastasis research has often focused on discrete elements of the metastatic process, such as the acquisition of an invasive and migratory phenotype with experimental systems mimicking intravasation and extravasation using advanced stage tumor models or accelerated metastasis models in murine systems. Improving physiologically relevant models that capture the entire metastatic process and further developing probes to track and monitor the in vivo dynamics of metastatic cell states would help facilitate understanding of the spectrum of metastasis. In patients with cancer, metastatic cells lie dormant or quiescent at the secondary site for weeks, months, or years, only to recoup proliferative ability and develop overt metastases that appear later in clinical progression and/or after primary treatment. The molecular, cellular, and tissue-level mechanisms that contribute to the early dissemination, dormancy, and eventual growth of detectable metastatic lesions are not well understood, and definitive in vivo measures of early metastasis and metastatic dormancy are needed to continue to propel the field to the next level.

Metastasis as a whole-body, systems-level challenge. The cooperation between the entire system or organism and multiple cellular phenotypes leading to metastasis and supporting metastatic outgrowth makes metastasis research a whole-body, systems-level/physiology challenge. Therefore, undertaking metastasis research using dynamic, holistic systems-level approaches —taking an integrated perspective that considers the whole organism —could generate mechanistic models that encompass dynamic biological scales, and provide opportunities to derive a more comprehensive picture of metastasis.

Research Objectives

Potential applicants are encouraged to visit the MetNet Website (The MetNet) or NIH Reporter (https://reporter.nih.gov/) to learn more about the research covered by the MetNet Centers. A diversity of approaches, cancers, and themes are of programmatic interest. Potential applicants are encouraged to contact NCI Program Staff before submission with questions regarding project goals and scope.

To promote integration with the MetNet Centers, projects should encompass one of the central themes defined in the MetNet FOA (RFA-CA-20-029). Moreover, specific areas of research encouraged by this initiative involve early dissemination and crosstalk as they apply to metastasis from organs such as lungs, prostate, pancreas, liver, kidney, bladder, or ovary; metastasis to sites such as the bone or lung or rare sites; and associated metastatic processes such as the establishment of, maintenance of, or emergence from dormancy. Investigations that explore mechanisms of metastasis in cancers with rising mortality rates and those that focus on disparate incidence and outcomes among patients from racially and ethnically diverse populations are highly encouraged.

Examples of individual research project topics that could fill the gaps within the current MetNet portfolio and cooperate towards a systems-level understanding of metastasis include, but are not limited to:

• Characterization of molecular and phenotypic signatures that define the dormant state in secondary organs or metastatic sites and/or how those molecules and phenotypes act in concert with the mechanisms underlying metastatic dormancy;
• Determination of cell intrinsic and/or microenvironmental factors that support the maintenance of a dormant state, dynamic phenotypic switching, and/or exit from metastatic dormancy;
• Determination of cell intrinsic and/or microenvironmental factors that define pre-metastatic niche conditioning or organ tropism;
• Examination of the role of stem-like or developmental cellular features that facilitate early disseminated tumor cells or emergence from the dormant state;
• Determination of the effect of standard-of-care or targeted therapies on promotion, maintenance, or emergence from a dormant state;
• Development of clinically relevant experimental models that concurrently address multiple dynamic and plastic steps in the metastatic process to organs such as the lung or bone;
• Studies that integrate metastasis with the macroenvironment;
• Development and application of novel tools to identify and track metastatic cells in vivo, including metastatic dormant cells, circulating tumor cells, or other micro- or macro- metastatic lesions to address mechanistic questions;
• Determination of cell intrinsic and/or microenvironmental factors that facilitate early dissemination of tumor cells including angiogenic, immunogenic, neurogenic, and other stromal cells and structural proteins from pancreas, lung, prostate, kidney, bladder, or ovary;
• Studies that advance and integrate an understanding of the role of signaling networks that mediate neural invasion to promote metastasis; and
• Determination of the mechanisms and impact of innervation across tissues and organs and how that influences dormancy and colonization.

Organization of Individual Research Projects and the MetNet

MetNet Expertise: The MetNet Centers involve transdisciplinary expertise that spans cancer biology, genetics, physical sciences, neurology, immunology, physiology, systems biology, and bioinformatics. To continue to promote collaborative opportunities and expertise sharing, this FOA encourages the use of the multi-PD/PI option, with a team having complementary expertise. A designated Resource and Data Sharing manager is required.

MetNet Organization: The MetNet will consist of the originally funded U54 Research Centers and all U01 Research Projects that will be awarded through this FOA. These entities will be governed by the MetNet Steering Committee, comprised of contact PIs, patient advocates, and NCI Program Staff.

MetNet Pilot Projects: To promote greater interactions across the Network and allow investigators to cross-test ideas, pursue intriguing observations or validate findings, MetNet Center and Research Project investigators are required to set aside funds in the out years for Pilot Projects. How Pilot Projects are structured and who may apply for such funds is at the discretion of the Center or Research Project leadership team. Such pilot projects are not required to be described in the application.

MetNet Patient Advocacy Community Engagement: Although not required for the MetNet Research Projects, the MetNet encourages the participation and support of patient advocates on research project activities when possible, including but not limited to, participation in research meetings, annual meetings, and engaging with research scholars to enhance their science communication. To learn more please visit: NCI Research Advocacy.

Resources Relevant to MetNet Research Projects

MetNet Research Project awardees will have the opportunity to take advantage of Network-wide working groups and will be expected to participate in Network-related activities with the MetNet community. Some of these activities will be facilitated through the NCI’s Division of Cancer Biology (DCB) Multi-Consortia Coordinating Center.

Non-Responsive Projects

The following types of projects would be considered non-responsive for the FOA, and applications meeting these criteria will not be reviewed:

• Projects that do not emphasis cancer metastasis;
• Projects that propose population-level epidemiology studies or clinical trials;
• Projects that duplicate on-going studies within the MetNet;
• Projects that emphasize developing therapies to treat metastases;
• Projects that do not apply systems-level approaches to a metastasis question; and
• Applications that propose multiple large projects or describe specific pilot projects.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

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)

Local 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)

Federal Government

• 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.

• System for Award Management (SAM)– 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.
  • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission. 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 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 diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women 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.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications)

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) 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.

Letter of Intent

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:

Joanna M. Watson, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6206
Email: [email protected]

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

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.

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

For this FOA, a team science approach incorporating different disciplines is encouraged, including expertise in metastasis and systems-level approaches. Also, a Resource and Data Sharing manager must be named in the application and have defined roles and responsibilities. This individual will participate in the Resource and Data Sharing Working Group and will facilitate interactions involving Resource and Data Sharing with the DCB Multi-Consortia Coordinating Center.

R&R or Modular Budget

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

For this FOA:

• The budget must set-aside at least $25,000 (direct costs) per year to support intra-network pilot projects for years 2 to 5.
• The budget should include funds to support travel for Network activities, including but not limited to supporting the travel and participation of PD(s)/PI(s) to the annual MetNet Investigators meeting. The annual meeting may be held at the NCI or recipient Institutions.

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: Clearly state the specific aims of the Research Project, including the overall theme being addressed and the rationale for systems-level approaches to be taken.

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.

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• The Sharing plan must address the NIH Genomic Data Sharing Policy if applicable, i.e., if the proposed studies will generate large-scale human or non-human genomic data.
• Data, software, and models generated from research supported by this FOA are expected to be shared across the network in accordance with MetNet policies. The resource and data sharing plan should address how the team intends to share data across the MetNet and with the DCB Multi-Consortia Coordinating Center. For more information see the Cooperative Agreement Terms and Conditions of Award in Section VI of this FOA.
• The resource and data sharing plan should describe the types of data, software, and models that are expected to be generated and shared, including the resources required to facilitate data sharing that are consistent with achieving the goals of this program.
• Data, software, and models generated from research supported by this FOA are expected to be shared in an easily accessible format to increase the value of the significant public investment. Program staff may negotiate modifications to these plans before funding of an award.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

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

Foreign Institutions

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.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. 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. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

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 and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

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.

5. Intergovernmental Review (E.O. 12372)

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 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 How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential fieldof the Senior/Key Person Profile form. 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 unique entity identifier provided on the application is the same identifier 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 and responsiveness by the NCI, NIH. Applications that are incomplete, non-compliant, and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.

Only the review criteria described below will be considered in the review process.  Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact

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

Scored Review Criteria

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? Is the prior research that serves as the key support for the proposed project rigorous? 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?

Specific to this FOA:

How well does the research theme of the proposed project address fundamental questions in metastasis research? How well does the proposed project address one of the priority areas defined by the FOA?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those 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?

Specific to this FOA:

How well does the research team demonstrate expertise in metastasis and systems-level approaches? How well does the research team incorporate necessary specialized research expertise? How well are the roles and responsibilities defined for the named Resource and Data manager?

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? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA:

How well does the overall research theme integrate perspectives and robust systems-level approaches to encompass the emergent properties of metastasis?

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?

Additional Review Criteria

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.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the 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 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.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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 individuals of all ages (including children and older adults) 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.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. 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 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)  Genomic Data Sharing Plan (GDS).

Specific for this FOA:

• How well does resource sharing plan detail what information, data, and models will be generated and how they will be shared across the MetNet and through the DCB Multi-Consortia Coordinating Center?

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the 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 will receive a written critique.

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.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. 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.

3. Anticipated Announcement and Award Dates

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. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

Section VI. Award Administration Information

1. Award Notices

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 recipient's business official.

Recipients 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.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.
• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 (DHHS) grant administration regulations at 45 CFR Part 75, 2 CFR Part 200, 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 recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH's 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 reside with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility:

• Overseeing the scientific research in the Research Project, analyzing and interpreting research data, reporting results to the scientific community, and disseminating approaches, methods, models, software, and tools broadly;
• Agreeing to be an active participant in the MetNet, including attending the Annual Investigators Meeting, participating in other network-sponsored meetings and workshops, and participating in collaborative activities;
• Promoting trans-MetNet and external collaborations to advance metastasis research;
• Serving on the MetNet Steering Committee. The MetNet Project PD(s)/PI(s) (contact PD/PI for applications with multiple PD(s)/PI(s)) are required to serve as members of the Steering Committee;
• Naming a designee to actively participate in the Resource and Data Sharing working group;
• Abiding by the governance of the MetNet and all program policies agreed upon by the MetNet Steering Committee and approved by NCI Program Officials to the extent consistent with the applicable rules and regulations;
• Reporting progress to the NCI Program Officials on all MetNet research and activities annually. The PD(s)/PI(s) may be expected to provide additional information, outside the scope of the standard reporting requirement, as needed and requested by program staff members on a semi-annual basis;
• Actively participating in the Resource and Data Sharing Working Group by the designated Data manager. This working group will be responsible for discussions regarding standard metadata fields, determine whether there will be pre-publication of data sharing across the MetNet, create SOPs for MetNet data upload in conjunction with the different NCI Cancer Research Data Commons, and lead the conversations about data quality control, cross validation, etc.;
• Ensuring that data are deposited in a timely manner in appropriate publicly available databases and that models, software, and other tools and resources developed as part of this Research Project are made publicly available according to MetNet policies;
• Ensuring that results of the Research Projects are published in a timely manner;
• Participating in the NCI-coordinated evaluation of the MetNet program;
• Organizing scientific working groups to facilitate collaborative pilot projects and validation of experimental concepts and observations; and
• Notifying NCI Program staff members about intra-network research pilot projects (those funded through restricted funds in the Project) selected (with information on the scope of these projects and how they can contribute to the overall research of the MetNet).

Recipients 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 DHHS, PHS, and NIH policies. Participating MetNet members are also encouraged to organize and participate in other Network meetings and workshops, organize collaborative activities, promote Trans-Network collaborations, and organize and participate in scientific and programmatic working groups.

NCI program staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. The substantially involved NCI program staff member(s), acting as Project Scientist(s), will coordinate in a centralized fashion various activity of the recipients. Specific responsibilities of the NCI Project Scientist(s) will include, but will not be limited to:

• Serving as voting members of the MetNet Steering Committee;
• Serving as a resource for the MetNet in making them aware of other ongoing NCI activities that may be relevant to the study or goals of the MetNet;
• Serving as a member of the Resource and Data sharing working group;
• Assisting the Steering Committee and individual MetNet recipients in avoiding unwarranted duplications of effort across the MetNet;
• Facilitating collaborative research efforts that involve multiple MetNet Research Centers.
• Assisting the recipients as a resource in facilitating their broader interactions with other NCI and NIH programs to disseminate results, tools, and models from the MetNet and take advantage of existing NIH/NCI resources and infrastructures;
• Evaluating the effectiveness and facilitating network-wide adoption of resource practices;
• Monitoring the operations of the MetNet recipients and making recommendations on overall project directions and allocations of MetNet Center funds;
• Reviewing the progress of the MetNet recipients;
• Participating in organizing annual MetNet meetings, specialized workshops, and webinars of the consortium;

In addition, an NCI Program Director acting as a Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility:

The MetNet will have a Steering Committee as the governing body. The MetNet Steering Committee will consist of the following:

• Contact PD/PI (for MetNet Research Projects with multiple PD(s)/PI(s)) from each awarded MetNet Research Project and Center;
• Patient Advocates from the MetNet Research Centers; and
• NCI Project Scientists.

Each member of the Steering Committee will have one vote. NCI Project Scientists have one combined vote. Additional NIH/NCI program staff and other government staff may participate in MetNet Steering Committee meetings as non-voting members. The structure is designed to allow awarded investigators and NCI staff to work together to facilitate trans-MetNet activities based on synergistic expertise and projects.

Two PD(s)/PI(s), representing two different MetNet awards (U01 or previously awarded U54 centers), will be selected to serve as chairs of the existing MetNet Steering Committee and serve a term of 1 year in that capacity. All MetNet Steering Committee decisions and recommendations that require voting will be based on a majority vote.

The Steering Committee may have additional non-voting members.

The MetNet Steering Committee will meet regularly and annually at the MetNet Annual Investigator Meeting.

The MetNet Steering Committee will:

• Identify scientific and policy issues that need to be, or can benefit by being, addressed at the Network level and develop recommendations to NIH/NCI Program Officials for addressing such issues;
• Review progress of the MetNet toward meeting the overall Network goals;
• Ensure that all MetNet administrative and data managers actively engage with the network;
• Coordinate dissemination of Network output to the broader cancer research community;
• Assist with planning the content of MetNet Annual Meeting.
• Review the potential of Shared Resource Core(s) at individual Research Centers to serve the needs of other Research Centers or Research Projects and develop appropriate policies for such activities;
• Ensure that the Network takes advantage of existing NCI and NIH resources and programs; and
• Establish, as necessary, subcommittees to ensure progress of the individual Centers, Projects, and the Network overall.

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: 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 recipient. This special dispute resolution procedure does not alter the recipient'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.

Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

3. Reporting

When multiple years are involved, recipients 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 RPPR, 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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients 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.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Joanna M. Watson, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6206
Email: [email protected]

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: [email protected]

Section VIII. Other Information

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 Part 75.