Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)

National Institute on Aging (NIA)

Funding Opportunity Title
Aging, Cancer-Initiating Cells, and Cancer Development (U01 Clinical Trial Not Allowed)
Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices
  • September 08, 2020 - Pre-Application Webinar for RFA-CA-20-040, Aging, Cancer-Initiating Cells, and Cancer Development (U01 Clinical Trial Not Allowed). See Notice NOT-CA-20-105.
Funding Opportunity Announcement (FOA) Number
RFA-CA-20-040
Companion Funding Opportunity

None

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.396, 93.866

Funding Opportunity Purpose

Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) and National Institute on Aging (NIA) will promote research to advance the understanding of the mechanistic factors and cellular interactions during aging that contribute to cancer initiation. Collaborations are strongly encouraged between scientists in the fields of aging biology and cancer biology. Applications should address key questions regarding how hallmarks of aging that lead to impaired cellular activities (metabolic alterations, proteostasis, epigenetic changes, and DNA repair) and alterations in the microenvironment (inflammation and immunosenescence) contribute to the development and outgrowth of cancer-initiating cells.

Key Dates

Posted Date
July 02, 2020
Open Date (Earliest Submission Date)
September 27, 2020
Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

October 27, 2020; February 17, 2021

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

February 2021; May 2021

Advisory Council Review

May 2021; October 2021

Earliest Start Date

June 2021; December 2021

Expiration Date
February 18, 2021
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) and the National Institute on Aging (NIA) intend to advance the current understanding of the mechanistic factors and cellular interactions during aging that contribute to cancer initiation.

Collaborations are strongly encouraged between scientists in the fields of aging biology and cancer biology. Applications should address key questions regarding how hallmarks of aging that lead to impaired cellular activities (metabolic alterations, proteostasis, epigenetic changes, and DNA repair) and alterations in the microenvironment (inflammation and immunosenescence) contribute to the development and outgrowth of cancer-initiating cells (CICs).

Background

Aging is the single, biggest risk factor for cancer. Cancer risk increases significantly in human after age 50, and half of all cancers occur in individuals over the age of 65. As a consequence of aging, cells accumulate DNA damage due to many factors such as genotoxic insults and altered DNA damage response pathways. For decades, researchers believed that the accumulation of mutations (mutation-centric theory) is the sole reason for cancer initiation. However, age-related mutations known to drive carcinogenesis can also occur in aged tissues in the absence of cancer suggesting that carcinogenesis is significantly influenced by yet unknown mechanisms of aging. New evidence suggests that these hallmarks of aging that lead to impaired cellular activities (e.g., metabolic alterations, epigenetic changes, DNA repair) and alterations in the microenvironment (e.g., inflammation and immunosenescence) contribute to the development and outgrowth of cancer-initiating cells (CICs) and those are the focus of this Funding Opportunity Announcement (FOA).
As people are increasingly living longer and therefore, more susceptible to age-associated disease, a better understanding of how aging-related changes in cell and tissue physiology impact the initiation and progression of cancer is needed and represents the focus of this FOA.

Research Objectives and Key Requirements

The overarching goal of this FOA is to support collaborative studies including cancer and aging researchers that address our limited understanding of the mechanistic factors and cellular interactions during aging that contribute to cancer initiation. Proposed projects must be focused on the mechanistic understanding of the age-related factors contributing to cancer initiation, and include collaborative efforts of aging and cancer experts. Use of aging models is strongly encouraged.
Research areas of interest to this FOA include, but are not limited to, the following:
Molecular mechanisms of age-associated changes in adult cell function and their links to cancer initiation: what are the cellular pathways and age-related molecular mechanisms that lead to the development of CICs ?

  • Molecular mechanisms of age-associated clonal expansion in somatic tissues: The hematopoietic system and the skin have been shown to exhibit major changes in clonal composition with age, such that a small number of clones harboring mutations in a group of genes can dominate the tissues over time. Many, but not all, of these mutations are implicated in cancer promotion. What are the mechanisms of clonal dominance that could lead to cancer initiation?
  • Contributions of the aging niche that promote tumor formation: The microenvironment is an important determinant of cellular function. What are the age-associated changes in the cancer-initiating cell microenvironment, such as senescence or an inflammatory milieu, that may contribute to tumor formation? How can we develop unique models to identify novel autonomous and nonautonomous factors that explore the role of aging in cancer initiation?
  • Epigenetic changes, including DNA/histone modifications and chromatin structure in aging cells and cancer: While some epigenetic signatures have been linked to the aging process, a systematic characterization of aging-related epigenetic changes in cells is lacking. Can the relationship of epigenetic changes to tumor susceptibility, initiation, and maintenance be established?
  • Aging-associated DNA damage response pathways and genomic instability in aged cells in cancer initiation: Genomic instability is closely linked to tumorigenesis. However, our understanding for how mutational processes change in old age, and how such changes contribute to cancer susceptibility, is limited. Are altered DNA repair capacity and responses to mutations in aged cells critically needed for cancer initiation?
  • Aging-associated metabolic changes and CICs: Alterations in metabolic signaling and the accumulation of both reactive oxygen species and harmful metabolites are thought to be significant components of aging cells. What is the contribution of metabolic changes in aged cells to cancer susceptibility and initiation?
  • Aging cancer rodent models to study the role of aging cells in cancer: Several genes expressed by adult cells have been studied that promote oncogenesis in transgenic mice. However, most studies of cancer are performed in young animals. What are novel models or how to improve current ones in order to study cancer cell biology within the context of aging?

Consortium Interaction and Meetings

PDs/PIs with expertise and experience in aging and cancer research are expected to work collaboratively to achieve the aims proposed in the application. PDs/PIs are also expected to attend yearly grantee meetings, including a kickoff meeting scheduled shortly after the awards are made, at which they will be expected to present proposed work, experimental models or interventions, and findings to other grantees. At the final meeting, grantees will be expected to report their findings and, together with other grantees, generate a summary of the program that will provide guidance to NCI and NIA's research communities about current understanding of the role of aging in cancer initiation.

Non-Responsive Applications

Applications with the following characteristics will be considered non-responsive.

  • Applications lacking studies and models that address both cancer and aging;
  • Applications lacking collaborations involving investigators with cancer and aging expertise;
  • Applications focused solely on biomarker identification;
  • Applications that solely focus on mechanisms of cancer maintenance or metastasis; and
  • Applications focused solely on epidemiologic and/or associative studies.

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

Section II. Award Information

Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed
Resubmission
New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?
Not Allowed: Only accepting applications that do not propose clinical trials

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The following NIH components intend to commit the following amounts in FY 2021:
NCI intends to fund either three or four awards, corresponding to a total cost of $2 million.
NIA intends to fund either five or six awards, corresponding to a total cost of $3 million.

Award Budget

Award budgets are limited to $300,000 per year in direct costs and must reflect the actual needs of the proposed project.

Award Project Period

The maximum project period is up to 5 years.

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

Eligible Organizations

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 Governments

  • 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
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed. 

Required Registrations

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) – 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.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons.Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 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.

Eligible Individuals (Program Director/Principal Investigator)

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.

2. Cost Sharing

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

3. Additional Information on Eligibility

 

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)

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 Guideexcept where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

 

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

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

  • Descriptive title of proposed 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:

Margaret Klauzinska, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5181
Email: klauzing@mail.nih.gov

Page Limitations

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

Instructions for Application Submission

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.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

Outline the multi-PD(s)/PI(s)' expertise in aging and cancer research and explain how the proposed research will be a collaborative effort that brings together aging and cancer experts without duplicating information in the biosketches. Also, elaborate on how the proposed project will bring together independent aging and cancer laboratories that will synergize in a combined effort to improve understanding of how aging contributes to the development of cancer-initiating cells (CICs). Explain how such collaboration will generate cross-fertilization between two fields of research, and how it will utilize a synergistic approach to tackling the ways in which aging promotes cancer initiation. Provide evidence that the members of the research team demonstrate the ability to work together in achieving project goals.

 

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

Salary/Effort: All applicants must follow the minimum level effort requirements for PD/PIs and project leaders for U01s as outlined in NOT-CA-20-047, which states that Principal Investigators (PIs), including Project Leaders on multi-project grants, will be required to commit a minimum level of effort of 1.8 calendar months (15% effort) for single PI applications and 1.0 calendar months (10% effort) each for multi-PI applications.

Travel: Applicants must budget funds for travel to attend a required workshop that will take place every year of the funded program in or near Bethesda, Maryland. The purpose of this annual 2-day meeting will be to bring together the extramural scientists on the funded projects to discuss progress in the program.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Significance

  • Indicate how achieving the goals of the proposed project will address the impact of age-related biological factors on cancer initiation.
  • Explain how the reciprocal interactions between one or more age-related biological factors promote the expansion of CICs.
  • State how successful completion of the proposed project leads to a better understanding of how an aged cell becomes a cancer-initiating cell.


Innovation

  • Indicate the novel mechanisms of cell and/or microenvironmental aging that drive the cancer initiation events investigated in the proposed project.
  • Specify whether innovative models and/or methodologies that address both aging and cancer research disciplines are used in the proposed study.


Approach

  • Describe how the proposed approaches synergistically combine knowledge and tools from both aging and cancer research communities.

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.
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-definedclinical 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.

PHS Assignment Request Form

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

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

4. Submission Dates and Times

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.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

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 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 and responsiveness by the NCI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Post Submission Materials

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

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.

 

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 proposed project consider the area of aging in the context of cancer initiation?

 

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?

 

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?

Specific to this FOA

How well does the application address novel cell aging mechanisms that drive cancer initiation? How well are the most innovative methodologies from both aging and cancer research disciplines employed to solve the problem stated in the study?

 

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 is the approach informed by current and emerging technologies associated with research on aging and cancer initiation? How well does the approach reflect knowledge of new trends in aging and cancer biology research?

 

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?

Specific to this FOA

How well does the proposed work bring together independent aging and cancer investigators that will synergize in a combined effort to improve understanding of how aging contributes to development of cancer-initiating cells?

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.

 

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

 

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.

 

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.

 

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.

 

Not Applicable

 

Not Applicable

Additional Review Considerations

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.

 

Not Applicable

 

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 Data Sharing Plan (GDS).

 

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.

 

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 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.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

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 submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or 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. Program priorities include the following:
    • PDs/PIs have appropriate expertise in aging and cancer research and work together to address how aging-related changes in cell and tissue physiology impact the initiation and progression of cancer-initiating cells (CICs);
    • Collaborative efforts that brings together aging and cancer experts that will generate cross-fertilization and utilize a synergistic approach to tackling how aging promotes cancer initiation

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 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.

Institutional Review Board or Independent Ethics Committee Approval: Grantee 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 awardee 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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

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. This includes ensuring programs are accessible to persons with limited English proficiency. 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 http://www.hhs.gov/ocr/civilrights/understanding/section1557/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.

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 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of the award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) 2 CFR Part 200 Administrative Regulations, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, NIH Grants Policy Statement (which implements the aforementioned HHS Regulations (45 CFR Part 75), 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 reside 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:

  • The PD(s)/PI(s) will have primary authority and responsibility to define objectives and approaches and to plan, conduct, analyze, and publish results, interpretations, and conclusions of studies conducted under this program.
  • The PD(s)/PI(s) assume responsibility and accountability to the applicant organization officials and to NCI and NIA for the performance and proper conduct of the supported research.
  • Specific responsibilities and rights include:
    • Defining objectives, approaches, and data analyses, and for preparation of publications for their projects.
    • Providing, in addition to standard annual progress reports (see Section VI.3. Reporting), other relevant information to the NIH Project Scientist(s) or Program Officer and coordinating and cooperating with NIH staff and other members of appropriate collaborating NCI and NIA and NIH programs.
    • Coordinating efforts among and cooperating with PD(s)/PI(s), co-investigators, and NCI and NIA program staff. These actions may involve (but will not be limited to) participation in appropriate coordinating meetings, working groups, and/or teleconferences, as needed.
    • Overseeing implementation of the approved data sharing plan and resource sharing plan; participating institutions/organizations will be expected to share knowledge, data, research materials, and any other resources necessary and relevant to their collaborations.
  • 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 DHHS, PHS, and NIH policies.

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

The designated NCI and NIA Project Scientists will have substantial scientific/programmatic involvement during conduct of this activity through technical assistance, advice, and coordination above and beyond normal program stewardship of grants, assisting in those aspects described below. The NCI and NIA Project Scientists will be the main contact for their respective institutes for all facets of the scientific interaction with the awardees and will provide advice to the awardee on specific scientific and/or analytic issues in addition to programmatic issues. As needed, additional NCI and NIA scientific staff members with relevant expertise may also become substantially involved as Projects Scientists/Coordinators. The responsibilities of substantially involved NCI and NIA Program Staff members will include the following aspects.

  • Provide technical assistance and advice to the awardees on specific scientific and analytical issues;
  • Facilitate collaborations between the awardees and other NCI- or NIA-sponsored programs investigators, or organizations;
  • Assist in avoiding unwarranted duplication of effort with other NCI and NIA efforts;
  • Monitor institutional commitments to and resources of the awardees;
  • Suggest reprogramming efforts, including options to modify projects/programs when certain objectives of this FOA are not met -- specifically, the NCI and NIA Project Scientist may recommend withholding of support, suspension, or termination of a U01 award for lack of adherence to required policies and/or procedures;
  • Develop working groups and trans-project efforts as needed;
  • Monitor progress and direction of awardees and working groups as needed;
  • Administratively manage the Steering Committee, organize meetings, and monitor implementation of its guidelines and procedures;
  • Organize and conduct regular meetings to share progress by teleconference and/or videoconference as needed amongst the U01 awardees, in addition to an annual face-to-face meeting of all awardees;
  • Make final decisions for the release of set-aside funds;
  • In addition, an NCI and an NIA Program Director acting as the Program Official will be responsible for the normal scientific and programmatic stewardship of the awards and will be named in the award notice.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

The NCI and NIA Project Scientists and the PDs/PIs of the Cooperative Agreement awards funded under this initiative will be jointly responsible for participating in initiative-wide activities and for establishing inter-project collaborations. In addition to the interactions defined above, the NCI and NIA Project Scientists and awardees shall share responsibility for the following activities via a Program Steering Committee, which will serve as a voting organizational body for the NCI, NIA, and awardees.

The Program Steering Committee will consist of the following voting members:

One representative of each awardee (each awardee will have one vote and the representative may be the contact PD/PI or a designated backup senior investigator); and

Two Project Scientists, one vote from NCI, and one vote from NIA.

A PD/PI will be elected to serve as chairperson of the Steering Committee. Chairperson serves 2-year terms. All Program Steering Committee decisions and recommendations that require voting will be based on a majority vote.

The Program Steering Committee will be organized and administratively managed by the NCI and NIA program staff and will meet once a year at NCI/NIA during the grant period where all grantees will be required to attend to discuss their progress, measures, and methodologic work. Additional webinar meetings will also be organized by the NCI in association with NIA program staff throughout the grant period. At the first meeting, grantees will work together under the guidance of NCI and NIA program staffs as a consortium of investigators to develop a collaborative approach to achieve the aims proposed in the application.

The NCI and NIA Project Scientists will serve on the steering committee. In addition, other NCI and NIA Program Officials may serve on the committee as non-voting members regarding quality control, protocol adherence, assessment of problems affecting the study and potential changes in the protocol, final data analysis and interpretation, preparation of publications, and development of solutions to major problems. The Steering Committee may establish working groups/sub-committees as needed, e.g., to address specific scientific or administrative issues.

Dispute Resolution:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the awardee, an NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

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 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.

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 agreementsare 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.

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threatensubmission 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:GrantsInfo@nih.gov(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:support@grants.gov

Scientific/Research Contact(s)

Margaret Klauzinska, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5181
Email: klauzing@mail.nih.gov

Candace Kerr, Ph.D.,
National Institute on Aging (NIA)
Telephone: 301-827-4474
Email: candace.kerr@mail.nih.gov

Peer Review Contact(s)

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


Financial/Grants Management Contact(s)

Amy Bartosch
National Cancer Institute (NCI)
Telephone: 240-276-6375
Email: amy.bartosch@nih.gov

Robin Laney
National Institute on Aging (NIA)
Telephone: 301-496-1473
Email: laneyr@mail.nih.gov

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.

Authority and Regulations

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.


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