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

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This Funding Opportunity Announcement (FOA) is a joint effort between the National Cancer Institute (NCI) and the National Institute on Aging (NIA) to promote research that will advance current understanding of the mechanisms by which aging impacts cancer onset, progression, metastasis, and therapeutic response. To maximize collaborative interactions for this program, NIH extramural scientists will collaborate with investigators in the NCI Center for Cancer Research (NCI CCR) and/or the NIA Intramural Research Programs (NIA IRP) to address key questions on the aging contribution to cancer. These collaborating NCI CCR and NIA IRP investigators should be tenured or tenure-track scientists with whom the NIH extramural NIH scientist has made prior contact regarding the collaborative project.

The incidence of most human cancers increases dramatically with advanced age. Cancer incidence is ten times higher in adults 65 or older compared to younger populations and this age group also has the highest mortality rate from cancer. Aging is characterized by the impairment of multiple cellular (including genome stability, epigenetic regulation, protein quality control, nutrient sensing, mitochondrial function, etc.) and systemic (response to paracrine or endocrine cues) functions. However, how aging-associated cellular impairments affect cancer etiology is not clear. Despite progress toward understanding the mechanisms that lead to cancer initiation and progression, how aging-associated processes contribute to cancer is largely unknown and a better understanding of the aging impact on the trajectory of cancer is needed to address the looming public health concern associated with populations that are increasingly living longer.

NCI and NIA will be joined in this effort by the Samuel Waxman Cancer Research Foundation (SWCRF). NCI, NIA and SWCRF have a shared interest in advancing research on aging in cancer and a private-public partnership has been established to jointly fund grants in this program. SWCRF is a private foundation that sponsors biomedical research focused on cancer and supports collaborative, team science to accelerate research discoveries and develop innovative cancer therapies.

Since the potential links between aging and cancer pertain to many research topics that are both basic and applied, studies in response to this FOA should be considered from the molecular, cellular, microenvironmental, and organismal perspectives. The goals here are to join cancer and aging expertise in the initiation of novel interdisciplinary research projects, shared resources and reagents and develop novel technologies and multi-dimensional approaches needed to address the role of aging in cancer.

In addition to incorporating aging and cancer components, suitable projects are expected to apply current expertise, experimental models, reagents, and tools to address significant questions that advance our knowledge of the aging contribution in cancer.

Research areas of interest to this Funding Announcement include, but are not limited to:

• The decline in tissue maintenance in old age a link to cancer incidence and an area for intervention: Given the lack of evolutionary pressure to maintain the somatic tissues beyond periods where reproductive success was likely, our bodies undergo decline in old age. The molecular mechanisms responsible for the aging-related changes in the function of major types of stem cells, such as hematopoietic, epithelial or mesenchymal stem cells, and their relationship to tumor formation are largely unknown. It will be important to understand the pathways that can be regulated to determine how modulation of these pathways can affect the evolution of cancer. Such studies could lead to the design of interventions to reduce cancer risk associated with old age.
• Molecular mechanisms of aging-associated changes in stem cell function and their relevance to cancer: In many tissues, cell differentiation and tissue homeostasis are characterized by a limited number of active stem cells. As an individual ages, the function and/or number of stem cells decreases.
• Mechanisms of clonal evolution in somatic tissues with age: 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 malignancy development. The mechanisms leading to clonal dominance and their importance for cancer promotion or inhibition are poorly understood.  
• Contributions of the microenvironment in aging-associated tumor formation: The microenvironment is an important determinant of cellular function. Aging-associated changes in the microenvironment, such as elevated levels of senescent cells and inflammation resulting from the senescence-associated secretory phenotype, may contribute to tumor formation with aging.
• Inter-organ system communication in aging and cancer: There is evidence that the aging hematopoietic system plays a role in the evolution/progression of solid tumors and cardiovascular diseases. The aging of other organ systems likely also has trans-effects and may affect the hematopoietic stem cell compartment and alter blood stem/progenitor function.
• Chromatin/Epigenetic mechanism in aging and cancer: While some epigenetic features have been linked to the aging process, a systematic characterization of aging-related epigenetic changes, including DNA/histone modifications and chromatin structure, is lacking and the relevance of these features to tumor susceptibility, formation and maintenance is largely unknown. In addition, mutations of epigenetic regulators are seen both in aging and cancer, but their causal relationship is unclear. Further, activation of endogenous retroelements has been observed in both aging and cancer, although the relevance of active retrotransposition to aging or cancer has yet to be established.
• Mutation and/or de-repression of non-coding genome regions in aging and cancer: Mutations in non-coding regions, including non-coding RNAs and regulatory elements, are now widely implicated in cancer. Non-coding mutations that affect aging-associated cancer mechanisms may exist.
• Aging-associated DNA damage response pathways and genomic instability in cancer: 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. Studies to determine whether DNA repair capacity and responses to mutations are altered in old age are critically needed.
• Aging-associated changes in metabolism in cancer: Alterations in metabolic signaling and the accumulation of both reactive oxygen species and harmful metabolites are thought to be significant components of aging. The contribution of these metabolic changes to cancer susceptibility, progression, and metastasis in addition to the possibility of using metabolic manipulations to affect carcinogenesis remain to be explored.
• Human premature aging disorders as model systems of aging-associated cancer formation: Human aging is notoriously difficult to study as model systems do not reflect the complexity of human biology and do not take environmental influences into account. Naturally occurring premature aging diseases are ideal systems to study the link between aging and cancer, particularly considering the differential rates of tumor occurrence among the various pre-mature aging disorders.
• Novel mouse models to study the role of aging in cancer: The mouse is the standard model for human blood and solid tumor malignancy. However, mouse and human aging differ in significant ways, and the aging process differs even between mouse strains. Development of genetically heterogeneous models of aging and cancer will facilitate the testing of therapeutic efficacy and side effects. In addition, and importantly, most studies of cancer are performed in young mice. Projects that study cancer biology within the context of aging mouse models are needed.
• Cellular mechanisms contributing to direct and inverse comorbidities in aging: Comorbidities, or the presence of more than one disease in individuals, is a key feature of aging humans and current studies suggest there are both direct and inverse relationships between age-related complex diseases. For example, epidemiological data have revealed a significantly reduced cancer incidence in patients with Alzheimer's and Parkinson's diseases (an example of inverse comorbidity). Understanding the mechanisms that underscore these types of disease-disease relationships in aging is essential for improving treatment strategies and therapeutics for aging populations.

Potential applicants are strongly encouraged to contact the NCI or NIA representatives listed in this announcement (see Section Vll) to discuss the appropriateness of the planned collaboration prior to submitting the application.

Additional information on the NCI Intramural Program (NCI IRP) may be found at https://www.cancer.gov/research/nci-role/intramural and at https://irp.nih.gov/about-us/our-programs/nia for the NIA Intramural Program (NIA IRP).

Individuals from underrepresented racial and ethnic groups, women, and persons with disabilities are encouraged to participate in this opportunity for supplemental support.

Consortium Interaction and Meetings

NCI and/or NIA IRP collaborators and the PD(s)/PI(s) on funded applications are expected to work collaboratively to achieve the aims proposed in the application. PD(s)/PI(s) and their collaborators on applications selected for funding are also expected to attend a virtual kickoff meeting where a presentation on the proposed work, experimental model or intervention will be made to other grantees, NCI, NIA and SWCRF. At time to be determined, PDs/PIs will be required to attend a final Program meeting to report their findings and together with other grantees, will generate a summary of the program which will provide guidance to NCI's and NIA's research communities highlighting NIH's interest in understanding the role of aging in cancer. For the purposes of budgeting travel expenses in the application it can be assumed this final meeting will be 2-day domestic meetings.

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

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

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

Governments

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

Other

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

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

Applicant Organizations

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

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

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

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

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

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

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

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

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

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

Buttons to access the online ASSIST system or to download application forms 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.

It is critical that applicants follow 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.

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

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

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

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

Letters of intent should be e-mailed to:

Chamelli Jhappan, Ph.D.
Division of Cancer Biology
National Cancer Institute (NCI)
Telephone: 240-276-6200
Email: jhappanc@mail.nih.gov

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.

NIA and NCI Intramural Research Program (IRP) Collaborator: An investigator from NCI Center for Cancer Research must serve as co-investigator, and collaborators from NIA and other divisions in NCI intramural research program are also encouraged. Intramural collaborators should be tenured or tenure-track scientists and should have had previous contact with the PD(s)/PI(s) regarding the collaborative project proposed in the application.

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

The budget proposed should reflect only the extramural PD(s)/PI(s) portion of the project. Extramural PD(s)/PI(s) may request up to $75,000 in direct costs per year for up to two years.

Travel: Applicants may budget funds for travel to attend a workshop that will be required in the second year of the funded program in Bethesda, Maryland. The purpose of this annual meeting will be to bring together the extramural, IRP collaborators and SWCRF co-sponsors on the funded projects to discuss the program outcome.

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:

Research Strategy:

This section should focus on the significance, specific strategies, innovation, approach, and environment and address the following: the scientific premise linking aging and cancer in the proposed studies; the novelty of the hypothesis and how the results will advance our current knowledge of the aging contribution to cancer processes; the distribution of the aging and cancer expertise among the investigators and how the collaboration between the PD(s)/PI(s) and the IRP collaborator is beneficial to the project

Letter of Support:

Because an investigator from NCI Center for Cancer Research must serve as co-investigator, and collaborators from NIA and other divisions in NCI intramural research program are also encouraged, include a letter of support (LOS) from the NIA and/or NCI IRP collaborating scientist. This LOS should be signed by the IRP Scientific Director, and indicate an agreement to undertake the components of the project designated to be performed in the IRP laboratory.

The LOS should also include the following items:

• The overview, hypothesis and aims of the overall project
• The reason for the PD(s)/PI(s) and IRP collaboration and the benefit gained from the collaboration
• The PD(s)/PI(s) and IRP Scientist's contribution to the project from the conceptual development to the practical aspects of achieving the goals of the project
• Because the IRP Scientist may request up to $75,000 per year for up to two years from the NIH Intramural Program, a budget outline for the IRP component of the project must be included.

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

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

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Use only for applications with due dates on or after January 25, 2018. When involving NIH-defined human subjects research, clinical research, and/or 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

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 (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions.

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.

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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

The requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the NIH Intramural Program. NIH intramural scientists will participate in this program as research collaborators or consultants in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above.

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.

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

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

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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 for this FOA: Does the proposed project consider the area of cancer research in the context of aging? If the aims of the project are achieved, how will our scientific understanding of the aging contribution to cancer processes be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive the research area of understanding the role of aging in cancer?

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 for this FOA: Do the PD(s)/PI(s) the IRP scientist have the appropriate expertise in aging and cancer research? Will a part of the project be conducted in either NIA and/or NCI IRP labs? Do the members of the research team demonstrate the ability to work together in achieving the project goals?

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 for this FOA: Will novel mechanisms of aging in cancer etiology be investigated in this application? Are the best innovative methodologies from both aging and cancer research disciplines employed to solve the problem stated in the study? Does the proposed work use novel concepts, approaches, or methods? Does the project challenge existing paradigms in aging in cancer or develop new methodologies, theories, or technologies?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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 children, justified in terms of the scientific goals and research strategy proposed?

Specific for this FOA: Is the approach sufficiently informed by current and emerging technologies associated with research in aging and cancer? Does the approach reflect knowledge of new trends in cancer and aging biology? Are statistical and biological (sex) variables discussed?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

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

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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.

Not Allowed

Not Applicable

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.

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

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

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NCI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Applications will be assigned on the basis of established 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.

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.

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

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

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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 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, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

PD(s)/PI(s)' Responsibilities:

• The PD(s)/PI(s) will have the primary responsibility for defining the research objectives, approaches and details of the project within the guidelines of the Funding Opportunity Announcement and for performing the scientific activity.
• The NIH Staff collaborator, an NCI and/or NIA IRP Scientist, cannot serve as the Principal Investigator on an extramural award . The responsibility for the planning, direction and execution of the proposed research project will be solely that of the NIH extramural PD(s)/PI(s) in close collaboration with the NCI and/or NIA IRP collaborator. 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:

• NCI and/or NIA IRP scientist(s) serving as collaborators:
• will be IRP tenured or tenure-track staff and provide substantial scientific expertise in the proposed research area independent of duties associated with programmatic stewardship for the project.
• may have primary responsibility for a specific aim within the proposed project, may develop a major database for the extramural collaborator, or may even participate in a multi-site project for prevention or epidemiology studies.
• may provide advice and technical assistance to the PD(s)/PI(s), may participate in monitoring the progress of ongoing research, and assist in the analysis, interpretation, and reporting of findings in the scientific literature and to the community at large and the public policy community within the Federal government though various media.
• is subject to the same publication/authorship policies as the official NIH publication policy governing extramural employees.

NIA and NCI Program Directors 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:

• All responsibilities are divided between awardees and NIH staff as described above.
• Program Staff may not a dual role project collaborator and program official/NCI or NIA program director.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the 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 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.

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

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

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

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

Chamelli Jhappan, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6200
Email: jhappanc@mail.nih.gov

Felipe Sierra, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-6402
Email: felipe.sierra@nih.gov

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

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: wolfreyc@mail.nih.gov

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.