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)

Funding Opportunity Title
Metabolic Dysregulation and Cancer Risk Program, Research Grants: a Transdisciplinary Approach to Obesity-Associated Research (U01 Clinical Trial Optional)
Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type
New
Related Notices

  • July 07, 2021 - Pre-application Webinar for Metabolic Dysregulation and Cancer Risk Program: a Transdisciplinary Approach to Obesity-Associated Research - RFA-CA-21-021 and RFA-CA-21-022. See Notice NOT-CA-21-094.

Funding Opportunity Announcement (FOA) Number
RFA-CA-21-021
Companion Funding Opportunity
RFA-CA-21-022 , U24 Resource-Related Research Project (Cooperative Agreements)
Assistance Listing Number(s)
93.393
Funding Opportunity Purpose

The National Cancer Institute (NCI) invites research grant applicationsfor transdisciplinary studies that will enhance our knowledge of the dynamics and underlying mechanisms that link obesity, metabolic dysregulation and increased cancer risk as part of the Metabolic Dysregulation and Cancer Risk Program. Through this Funding Opportunity Announcement (FOA), the Metabolic Dysregulation and Cancer Risk Program will focus on metabolic dysregulation as the key process linking obesity with cancer risk.

For the purpose of this FOA, metabolic dysregulation is defined as alterations in glucose utilization and storage, insulin sensitivity, and/or lipid metabolism. Applications should specifically seek to advance our understanding of how metabolic dysregulation in individuals affects cancer risk and identify mechanisms that will enhance (i) cancer risk prediction, (ii) screening for high-risk individuals in clinical settings, and (iii) identification of potential targets for preventive and therapeutic interventions.

This FOA is published in parallel with RFA-CA-21-022 “Coordinating Center for the Metabolic Dysregulation and Cancer Risk Program: a Transdisciplinary Approach to Obesity-associated Research (U24 Clinical Trial Not Allowed)”. The individual research grants and the Coordinating Center funded under these FOAs together will constitute the Metabolic Dysregulation and Cancer Risk Program.

Key Dates

Posted Date
July 06, 2021
Open Date (Earliest Submission Date)
September 06, 2021
Letter of Intent Due Date(s)

September 1, 2021

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
October 06, 2021 Not Applicable Not Applicable March 2022 May 2022 July 2022

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.

No late applications will be accepted for this Funding Opportunity Announcement (FOA).

Expiration Date
October 07, 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

Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) invites research grant applications for transdisciplinary studies that will enhance our knowledge of the dynamics and underlying mechanisms that link obesity, metabolic dysregulation and increased cancer risk. Investigators funded through this FOA, together with the Coordinating Center (funded through the companion FOA, RFA-CA-21-022), will constitute the Metabolic Dysregulation and Cancer Risk Program. The Metabolic Dysregulation and Cancer Risk Program will function as a Consortium to advance the vision and goals of the initiative, which includes a deeper understanding of the effects of obesity-associated metabolic abnormalities and their links to cancer risk. This improved understanding will inform the development of targeted interventions designed to prevent, reverse, and/or slow progression of obesity-associated cancers.

The short-term scientific goals of the Metabolic Dysregulation and Cancer Risk Program include: (i) understand the mechanisms by which obesity-related metabolic dysregulation (defined as alterations in glucose utilization and storage, insulin sensitivity, and/or lipid metabolism) affect cancer initiation and development; (ii) develop common measures for obesity-related metabolic dysregulation across specific cancer types; (iii) define critical signal pathways between biologic processes (e.g., insulin resistance and inflammation) that regulate obesity-associated metabolic alterations and cancer risk; and (iv) determine the utility of emerging approaches for the discovery of novel obesity-associated metabolic targets in cancer risk and prevention.

 

Key Terms and Definitions for this FOA

  • Metabolic Dysregulation: For the purpose of this FOA, metabolic dysregulation is defined as any sustained alteration in glucose utilization and storage, insulin sensitivity, and/or lipid metabolism.
  • Metabolic Dysregulation and Cancer Risk Program: Refers to the NCI coordinated activities, funding and stewardship of research activities related to the metabolic dysregulation and cancer risk initiative. The initiative is a consortium comprised of research teams from individual research grants and Coordinating Center, activities facilitated by the Coordinating Center, and guidance from NCI Program Staff. The term "Consortium" may be used to reference the Metabolic Dysregulation and Cancer Risk Program hereinafter.
  • Steering Committee: The Steering Committee will be established and will comprise of representatives from the funded individual research grants, the Coordinating Center, and NCI Program Staff. It will govern the Metabolic Dysregulation and Cancer Risk Program through regular meetings, coordinated activities, and communications. The Steering Committee will lead, prioritize, and coordinate collaborative scientific activities and efforts to facilitate scientific synergy within the Consortium. Activities may include: i) recommendations for common measurements of exposures and/or endpoints; ii) collection of scientific data; iii) and coordinating efforts across two or more individual research grants (e.g. pilot projects linking unique resources).
  • Coordinating Center: Refers to the Coordinating Center funded through the companion RFA-CA-21-022.

Background

Obesity as a public health concern

Obesity (i.e., a state of chronic positive energy balance) is an established risk factor for multiple cancers, and emerging data links obesity to the early onset of several types of cancer. The obesity-cancer link is a pressing concern due to the escalating prevalence of obesity, especially in Western populations. In addition, the burden of obesity-associated cancer is unequal, as it afflicts certain communities in the United States, specifically racial/ethnic minority populations at greater rates than the overall population.

Obesity and metabolic dysregulation

Epidemiologic findings indicate that cancer risk may be lower among metabolically healthy overweight/obese individuals compared to overweight/obese individuals with metabolic dysfunction. Thus, it has been hypothesized that cancer susceptibility associated with obesity may be due to sustained metabolic dysregulation, rather than the adiposity per se. Both preclinical and clinical studies indicate that hypoglycemia reduces tumor incidence. For example, in animal models prolonged reduction in daily caloric intake or daily intermittent fasting (to reduce glucose availability) has been shown to reduce cancer incidence. In clinical studies, intermittent fasting (IF) decreases insulin resistance, lowers levels of IGF-1, leptin, and glucose, and increases adiponectin, all of which are linked to a decreased risk of several malignancies. Weight-loss interventions such as bariatric surgery in severely obese individuals have also been shown to lower risk of several obesity-associated cancers (e.g., postmenopausal breast cancer, endometrial cancer, colon cancer) and to influence their metabolic health (e.g., decrease insulin resistance).

Obesity creates a chronic disease-susceptible state

Obesity can be conceptually viewed as a “disease-susceptible state” and/or a “metabolically dysregulated state.” This state of disease predisposition can progress to several chronic pathologies, including cancer. Chronic disease states in which obesity is a known contributor (e.g. type 2 diabetes mellitus, non-alcoholic fatty liver disease [NAFLD], and metabolic syndrome) share biomarker profiles (insulin resistance, hyperinsulinemia, inflammation, hyperglycemia, and dyslipidemia) that reflect metabolic dysregulation, and that plausibly contribute to the initiation and development of obesity-associated cancers through unknown mechanisms.

Gaps in knowledge

Obesity-associated etiologic pathways are likely to be heterogeneous and to vary by severity and duration of obesity, cancer type, and by the metabolic dysregulation specific to the individual. Studies of endogenous and exogeneous factors with discrete impact on obesity, metabolic functions, and cancer risk are needed to understand the molecular interactions between obesity-associated metabolic dysregulation and critical biologic pathways (e.g., inflammation, sex hormones, adipokines) that impact cancer risk. These factors include, but are not limited to, local and systemic immunomodulatory effects of the gut microbiota, sleep cycle, and environmental exposures (phthalates, dietary metabolites). How these factors influence the obesity-metabolism-cancer relationship remains poorly understood and offers an opportunity to identify novel targets for new prevention and treatment strategies.

To address the lack of data and specimens from human studies of obesity-induced metabolic dysregulation and cancer risk, and increase the clinical relevance of pre-clinical models (e.g. animal or computational models), applicants should propose approaches that use observational or interventional human studies and, when feasible, include well-powered representation of racial/ethnic minorities and understudied populations to sufficiently address the unequal burden of obesity-associated cancer in those populations.

 

Specific Research Objectives and Requirements

Applicants responding to this FOA are strongly advised to review all components of this FOA for specific guidance and requirements, including:

  • Familiarize themselves with the companion FOA (RFA-CA-21-022) for the Coordinating Center to avoid duplicative allocation of budget for services (i.e. biostatistical needs) provided by the Coordinating Center. As the U01 awardees will interact closely with the Coordinating Center, the applicants responding to this FOA, therefore, need to understand the role and responsibilities of the Coordinating Center.
  • Understand the required participation in cross-Consortium activities as part of Metabolic Dysregulation and Cancer Risk Program as outlined below in "Cross-consortium Activities" and Section VI.2, Cooperative Agreement Terms and Conditions of Award.
  • Share de-identified data and metadata to a controlled-access data repository when appropriate, either an NIH data repository or repository with equivalent access. Data and resources must follow data and resources guidelines according to FAIR Data Principles (see https://www.go-fair.org/fair-principles/). If applicable, investigators are expected to evaluate and document compliance with NCI’s Best Practices for Biospecimen Resources for the collection, processing, and storage of biospecimens (https://biospecimens.cancer.gov/bestpractices/).

Responsive applications should include an observational or interventional study aim to address the initiative's primary focus on research in humans. As such, research proposal with clinically relevant experimental models (e.g. animal, computational, or in vitro) should be integrated with human data and/or human samples. Thus, applicants may propose to test a hypothesis using complementary, transdisciplinary approaches that incorporate experimental models with human studies (defined as research involving individuals or groups of individuals or data from humans). Usage of existing human specimens is permitted as appropriate by the scientific hypothesis investigated.

Applications submitted to this FOA that meet the National Institutes of Health (NIH) definition of a clinical trial: "a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes" (see NOT-OD-15-015 for more details)l are expected to follow the NIH Policy on Good Clinical Practice (see NOT-OD-16-148).

To meet the research goals of this program, all research applications must:

  • Proposed research aims must provide a well-developed hypothesis related to metabolic dysregulation and cancer risk with appropriate well-powered (adequate sample size and associated power calculation) study design to address the main research objectives and components (see below).
  • Application must address directly the relevance of the application to obesity-associated cancer research.
  • Proposed research should incorporate objective measures of obesity, such as visceral and central adiposity, which are more scientifically relevant than body mass index. Investigators are encouraged to include biologic ADOPT Core Measures to enhance data harmonization (https://www.nhlbi.nih.gov/science/adopt). Justification will be required if body mass index is the only proposed measure of adiposity.

Individual research project grants should address one or more of the following main research objectives:

  1. Investigate molecular mechanisms that define how metabolic dysregulation impacts obesity-associated cancer risk;
  2. Characterize an altered metabolic profile (e.g., metabolic-related markers) that identifies at-risk individuals;
  3. Test interventions designed to modify obesity-associated metabolic pathways to decrease cancer risk.

Specifically, proposed research projects may seek to understand and/or address the following components:

  • The etiologic role of metabolism-related phenotypes (e.g., insulin resistance, hyperinsulinemia, adipokines, dyslipidemia, growth factors, inflammation), and their impact on cellular abnormalities (e.g., dysregulated insulin/growth factor/cytokine signaling, cell fate, mutation and epigenetic changes) during cancer development;
  • How molecular profiles that reflect a metabolic-dysregulated state affect cancer susceptibility markers (genetic abnormalities including mutations and double strand breaks, or metabolite pools); and
  • Preventive interventions using modifiable factors (e.g., exercise, sleep, dietary patterns such as time-restricted feeding, probiotics, metformin) that may modulate cancer risk driven by metabolic dysregulation.

Areas of prioritization: This RFA will prioritize research focused on the role of insulin resistance and how it affects cancer risk and investigations on the crosstalk between obesity-associated metabolic abnormalities with key biologic processes, such as low-grade inflammation, and how they mediate cancer risk. Inclusion of participants with different racial and ethnic backgrounds will receive focused attention.

Examples of relevant research questions include, but are not limited to, the following:

Mechanism-related:

  • What are the biologic mechanisms underpinning obesity-associated metabolic dysregulation and cancer?
  • How does obesity/weight loss modulate altered metabolic pathways in cancer development?
  • How does metabolic dysregulation promote cancer development across the age spectrum?
  • What is the influence of biologic processes (e.g., inflammation, oxidative stress, hormones) on metabolic dysregulation and/or cancer risk?

Etiology/Epidemiology-related:

  • Are disease(s) linked to metabolic dysregulation causally associated with susceptibility for certain cancer types? What are the mechanisms underlying the association? What is the relationship of timing and duration of obesity to onset of metabolic disorders and subsequent cancer risk?
  • How do modifiable factors (e.g., circadian disruption, microbiome, diet, environmental factors) influence metabolic-related markers (e.g., insulin resistance, hyperinsulinemia, metabolic syndrome, adiponectin:leptin ratio) that lead to metabolic dysregulation and/or cancer risk?
  • What obesity-related risk factors influence metabolic-associated disease development of cancer across various geographic areas, socioeconomic groups, or racial/ethnic groups (e.g., ancestry)?
  • Are overweight/obese individuals with a metabolic dysregulation profile at higher risk of cancer compared to overweight/obese or nonobese people with a normal metabolic profile?

Intervention-related:

  • Can weight loss or other clinical interventions improve abnormal metabolic profiles such as insulin resistance so as to modify cancer risk and progression to cancer?
  • Can certain modulating factors (e.g., sleep, microbiome, diet, physical activity) and their putative interactions serve as interventions to attenuate the negative effects that obesity has on metabolic health and cancer?
  • Can chemopreventive agent(s), with or without dietary modification, improve the metabolic profile of at-risk obese/overweight patients and thereby decrease cancer risk?

Cross-consortium Activities

To facilitate synergy within the Consortium to achieve unmet scientific priorities of the Metabolic Dysregulation and Cancer Risk Program, award recipients are required to participate in cross-Consortium activities and identified pilot projects as recommended by the Steering Committee. The cross-Consortium collaborative activities will be developed and conducted by award recipients post-award as part of the Collaboration Core coordinated by the Coordinating Center and supported by set-aside Collaborative Funds (see Section IV.2, R&R and Developmental/Pilot Projects for further details). Activities may include, but not be limited to:

  • Identify common measures/targets that can be incorporated between at least two research project grants to facilitate downstream pool analysis and investigations within the Consortium.
  • Identify commonalities in research directions and specific questions being explored across the Consortium to promote cross-initiative collaborative efforts.
  • Identify a scientific problem (i.e. cross-consortium pilot project) that could be jointly explored across research project grants during the lifespan of the Consortium.

Developmental/Pilot Projects

Collaborative Funds (see Section IV.2. R&R and Budget for further details) can be used to support the expansion or inclusion of an exploratory aim to incorporate identified common measures or targets, develop new methodologies that can be validated via multiple grants, or facilitating diverse study population. This restricted fund may be combined with other award recipients' Collaborative Fund. Collaborative Funds may also be used to fund cross-Consortium pilot projects or developmental ideas with one or more award recipients within the Consortium and may involve outside investigator(s) (not recipient within the Consortium). The outside investigator(s) must bring a desirable expertise that is not already part of the Consortium and must meet the purpose of the Metabolic Dysregulation and Cancer Risk Program. The inclusion of outside investigators will require appropriate justification and approval from the Steering Committee. Proposed pilot projects without the inclusion of other award recipients are considered ineligible for the use of Collaborative Funds. Collaborative Funds should not be used for activities that have been supported under the awards for individual research project grants and outside the scope of the outlined goals of the initiative. Usage of Collaborative Funds to enable conduct of multi-year cross-consortium pilot project or activities are allowable. The Coordinating Center may choose to use its Collaborative Fund to provide educational opportunities (e.g. travel awards) for early-stage investigators or students to the Consortium's meetings.

Structure of the Metabolic Dysregulation and Cancer Risk Program

The Metabolic Dysregulation and Cancer Risk Program will include four to five individual research project grants with expertise that cuts across basic science, metabolism, oncology, epidemiology, and intervention/prevention research and a Coordinating Center (funded via RFA-CA-21-022). As such, the initiative seeks to fund a consortium of research investigations that incorporates a transdisciplinary approach that would not have occurred with a traditional single-disciplinary investigation.

Upon successful funding, award recipients will be required to participate in a virtual kick-off meeting which will take place within a month of the release of the NOA. Recipients will be required to attend a yearly face-to-face annual meeting and other topic-specific smaller meetings (as appropriate) for the exchange of scientific information across the Consortium. The Coordinating Center (RFA-CA-21-022), in conjunction with NCI staff, will facilitate cross-Consortium collaborations across the individual research project grants. The Metabolic Dysregulation and Cancer Risk Program will be governed by a Steering Committee comprised of representatives from the funded individual research grants, the Coordinating Center, and designated NCI Program Staff members.

Award recipients will be required to interact closely with the Coordinating Center and NCI program staff to advance scientific research related to metabolic dysregulation and cancer risk, as outlined below.

  • Scientific interactions with Coordinating Center and NCI program staff: Each research project grant will collaborate with the Coordinating Center as required to identify common measures as related to markers of metabolic dysregulation (e.g., insulin resistance), incorporate identified common measures and, as appropriate, share protocols for the collection of biological specimens.
  • Scientific interactions with Steering Committee: The Steering Committee will establish Work Groups intended to provide a forum for discussing and advising on topic areas that overlap all research from the Consortium. Members of the Work Groups will include investigators from each individual research project grant, Coordinating Center, NCI Program Staff, and other ex-official with complementary expertise.

Governance

The Steering Committee will comprise of the PI of each research grant, the PI of the coordinating center and designated NCI program staff. Though the Steering Committee will make recommendations, NCI Program Staff will have final authority to approve or reject any proposed recommendations. All Consortium-related activities must comply with NIH, DHHS, and Federal Guidelines. Designated NCI Program Staff, as per the cooperative agreement mechanism, have substantial scientific and programmatic authority beyond the normal grant stewardship to guide scientific direction and direct efforts to optimize synergy, scientific impact, and productivity of the Metabolic Dysregulation and Cancer Risk Program.

Additional details on the composition and functions of the Steering Committee are provided in Section VI.2, Cooperative Agreement Terms, and Conditions of Award.

Non-Responsive Applications

The following types of activities remain outside the scope of this FOA, and applications proposing them are non-responsive to this FOA and will not be reviewed.

  • Studies that do not seek to investigate cancer risk or markers of carcinogenesis;
  • Studies that do not seek to examine recognized markers of metabolic dysregulation;
  • Approaches that include only animal/pre-clinical models with no inclusion of a human population or human samples;
  • Applicants that do not provide explicit adherence to data/resource sharing plans and not following FAIR principles (see https://www.go-fair.org/fair-principles/) for Resource Sharing Plans.

NOTE: Applicants to this FOA or the companion RFA-CA-21-022 are strongly encouraged to attend at least one of two planned pre-application webinars sponsored by the NCI and contact NCI staff as soon as possible in the development of the application (preferably no later than 12 weeks prior to the application due date) to discuss the details of their proposed study so that NCI staff can help the applicant understand whether the study is within the goals and mission of the Institute and is appropriate for this FOA.

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
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?

Optional: Accepting applications that either propose or do not propose clinical trial(s).

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

NIH intends to fund four to five awards, corresponding to a total of $5.6M, for fiscal year 2022. Future year amounts are anticipated to be at the same levels but will ultimately depend on annual appropriations.

Award Budget

Application budgets may not exceed $850,000 in direct costs per year (excluding sub-award F&A costs) and must reflect the actual needs of the proposed project.

Award Project Period

Total project period may not exceed 5 years.

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

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time.  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 Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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

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

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

The letter of intent should be sent to:

Tram Kim Lam, PhD, MPH
National Cancer Institute (NCI)
Telephone: 240-276-6967
Email: lamt@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.

R&R or Modular Budget

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

Restricted Collaborative Funds for Cross-Consortium Activities and Pilot Projects: To facilitate synergy within the Consortium to achieve unmet scientific priorities of the Metabolic Dysregulation and Cancer Risk Program, each research project grant must budget appropriate funds as "Collaborative Fund” to facilitate cross-Consortium activities (see Section VI.2 Cooperative Agreement Terms and Conditions of Award). Applicants to this FOA must budget up to $25,000 or 10% (whichever is greater) in direct cost per year and this restricted fund must be allocated as Collaborative Fund (to be presented in the Other Expenses category under the heading "Collaborative Fund"). During Year 1 of the Consortium and in consultation with NCI Program Staff, flexibility is allowable for modification of the proposed Specific Aims and associated milestones. Carryover of Year 1 Collaborative Fund is permitted with approval from NCI Program Staff. Collaborative Fund cannot be re-budgeted and unobligated fund, in any year, may be offset as per the recommendation from NCI Program Staff. NCI will retain the final approval for the release of any Collaborative Funds.

Travel Funds: The budget should include funds to support travel for Consortium-related activities, including but not limited to supporting the participation of PD(s)/PI(s) and other U01 members in annual meetings. Specifially, applicants will be required to budget for a key personnel member and team members/collaborators (in aggregate, up to three members) to attend one face-to-face investigator meeting per award year during the grant cycle. Each funded research project grant should plan to host one annual/scientific meeting with appropriate meeting support and assistance from the Coordinating Center during the life cycle of the Consortium.

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:

Specific Aims: All applications must include research aims focused on an objective measure of metabolic dysregulation and endpoints relevant to cancer risk/incidence or critical to assessing modulation of cancer risk. All applications must include at least one human-based research aim. Applications may include an experimental research aim using in vivo or in vitro models. Explain how the findings of the project and/or individual aims will be translated (either to inform future cancer prevention strategies, interventions, public health guidelines to decrease the cancer burden of people in the United States) or to back-translate into pre-clinical models to inform mechanistic insights.

  • For the human-based Specific Aim: A human study is defined in this FOA as research that directly involves individuals or groups of individuals or that uses data from humans, such as information on their behavior or samples of their tissue. The application should describe the underlying hypotheses to be addressed by the proposed human study research and how they relate to the overall research theme of the application. Applications should also include relevant background information specific to the human study proposed, including but not limited to, supporting literature, biological rationale and supporting preliminary data as well as provide details on and a justification for the specific human study approach proposed.
  • For Specific Aim with pre-clinical models (e.g., animal): The applicant should describe the underlying hypotheses to be addressed by the proposed experimental model research and how they relate to the overall research theme of the application. Applications should also include relevant background information specific to the proposed model, including but not limited to, supporting literature, biological rationale and supporting preliminary data that provide justification and clinical relevance for the specific experimental research approach proposed.
  • For Specific Aim with clinical trials: Justify and explain the rationale for selection of the study population/geographic regions and if not including a human population, provide the scientific rationale for the human samples to be used.

Research Strategy: Applicants must organize the Research Strategy into the subsections identified below. Applicants may include other sections as needed but must include the information requested below.

Sub-section A. Background and Significance:

  • Provide an overarching rationale of why the proposed research is relevant to obesity-associated research and indicate the transdisciplinary nature of the proposed approach to understand the etiology of cancer risk.
  • Provide an overview of relevant scientific literature and the relevance of the pursued hypothesis to the relationship between metabolic dysregulation and cancer risk.
  • Identify the novel scientific gap fulfilled by the proposed projects with well-developed hypothesis addressing at least one of the objectives of the Metabolic Dysregulation and Cancer Risk Program.

Sub-section B. Preliminary Data

  • Summarize appropriate preliminary data;
  • Summarize history of collaboration across multiple disciplines.

Sub-section C. Approach

  • Describe methods that will be used to accomplish Specific Aims;
  • Describe the proposed measures of metabolic dysregulation and/or profile;
  • Describe the measure(s) of adiposity. If an objective measure is not proposed, provide a well-justified rationale;
  • Describe the analytic plan, including calculations for sample size and power analyses for each aim if appropriate. When possible, provide power calculations for any specific aims using racial/ethnic populations.

Sub-section D: Data Sharing and Dissemination

Applicants must provide a detailed plan for the facilitation of data and resource sharing (see Resource Sharing Plan).

Health Disparities. If applicable to the type of research being proposed, address how health disparity populations will be integrated into the proposed studies. Highlight, as relevant, any opportunities that, if implemented, can reduce the burden of cancer in the health disparities that currently exist. In this context, efforts are encouraged to address the needs of racially/ethnically diverse populations and those from urban and rural areas who are poor and medically underserved, who continue to suffer disproportionately from certain cancers and have higher morbidity and mortality rates. For clinical trials, anticipated milestones should be noted.

All applicants should state their willingness to collaborate in cross-Consortium activities and share information and resources among members of the Consortium, and briefly describe how the proposed research models, human study populations, or other unique aspects of the project could be leveraged to enhance the overall Consortium.

Letters of Support: Applicants must include letters of support from collaborating entities that are essential to the mission of the work proposed.

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide. No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

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

The following modifications also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. The data/resource sharing plans must be consistent with NIH policy and follow Findable, Accessible, Interoperable, Reusable (FAIR) principles (see https://www.go-fair.org/fair-principles/). Instructions for the Resource Sharing Plan is provided in the SF424 Application Guide. The plan should include steps for creating standard operating procedures, accessibility requirements, and review process for granting access to the research community, and dissemination of that information.
  • Data Sharing Plan should be consistent with accomplishing the goals of the Consortium, including
    • Data Sharing Plan should acknowledge that the Coordinating Center will be required to accommodate data, as identified by the Steering Committee as a common data element, to be upload from awardees of the individual research project sites and upon request from NCI Program staff.
    • Data Sharing Plan should acknowledge that the Coordinating Center will be required to make available data sets constructed for activities and projects approved by the Steering Committee.
    • Data Sharing Plan should acknowledge that the Coordinating Center will be required to make available all of their data from any Pilot Projects and collaborative activities, as approved by the Steering Committee, to the Awardees of the individual research grants.
    • Data Sharing Plan should acknowledge that the Coordinating Center will be required to make available algorithms produced for harmonization, standardization, and analyses of common data elements, and any new data deriving from pilot/collaborative projects, will be released and shared.
  • Sharing Additional Resources: Consistent with achieving the goals of this program, all resources generated (e.g., standards and SOPs) by the Awardees of the Consortium will promptly become available through a Coordinating Center resource. It is anticipated that other distribution avenues will be made available by the NCI if determined to be necessary.
  • NCI Program Staff may negotiate modifications to these plans prior to funding or post-award.
  • Intellectual Property Policy: Consistent with achieving the goals of this program and maximizing the benefit of all research funded as part of the Consortium for the improvement of public health through discoveries of the scientific community, the Data Sharing and Data Release policies expect a broad freedom-to-operate for all users of data generated by members and/or collaborators of the Consortium (e.g., by rapidly making data and results available in the public domain).
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-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

For applicants submitting a project which includes a clinical trial, a Milestone Plan must be included. While final milestones will be determined at the time of grant award, the applicant should propose clear milestones that provide objective outcomes that justify continuing the project. The milestones must include a timeline listing quantitative achievable goals for the study start-up, implementation and completion of the project as follows:

  • Completion of start-up activities (finalization of protocol, contracting of sites, registration in Clinicaltrials.gov, completion of regulatory approval, if applicable).
  • Enrollment of the first subject, and of 25%, 50%, 75%, and 100% of the projected recruitment. Additional requirements may be applied for minority recruitment at specific time points.
  • Expected timing of the proposed interim analysis and, for adaptive trials, implementation of the pre-specified adaptation plan, if applicable.
  • Completion of the data collection time period and primary and secondary data analyses.
  • Publication of primary trial results and reporting of results in ClinicalTrials.gov.
  • If milestones are not achieved fully, NCI may request development of a remedial plan and more frequent monitoring of progress, and/or take other remedial actions.
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 components of participating organizations, 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.

For applications involving clinical trials: A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Overall Impact

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

Scored Review Criteria

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

Significance

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

Specific to this FOA: Are the proposed transdisciplinary research activities likely to accelerate understanding of the link between metabolic dysregulation and obesity-related cancer risk, the underlying mechanisms, and the potential for prevention strategies?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA: Successful applicants will function collaboratively within the Consortium. Award recipients are required to work together to develop procedures and protocols (e.g., data sharing, publication) as relevant to the effective and efficient operations of the Consortium.

  • How well do the investigators demonstrate previous work in a transdisciplinary team?
  • How well does the application describe a history of collaboration and willingness to participate in team science and share information, and level of engagement in collaborative activities as members of the Consortium?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Innovation

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

Specific to this FOA: How well does the application describe how the proposed novel transdisciplinary methods, insights, and/or research approaches would not have occurred with a traditional single-disciplinary investigation?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

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

Specific to this FOA: If relevant, how well integrated are the proposed pre-clinical research aim and the human research aims? How well described are the steps proposed to disseminate applicable findings in appropriate formats to relevant stakeholders?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Environment

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

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

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.

 

Study Timeline

Specific to applications involving clinical trials
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable.

Renewals

Not Applicable

Revisions

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.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

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

 

As part of the scientific peer review, all applications will receive a written critique.

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.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

Section VI. Award Administration Information

1. Award Notices

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

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

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.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all 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.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities. 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) administrative guidelines, 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 award recipientsis anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the award recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have primary responsibility for: The PD/PI (or multiple PDs/PIs, if applicable) will have primary authority and responsibility to define objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of projects conducted. The PD/PI assumes responsibility and accountability to the applicant organization officials and to the NIH for the performance and proper conduct of the proposed research in accordance with terms and conditions of the award.

All PD(s)/PI(s) of the Metabolic Dysregulation and Cancer Risk Program (Coordinating Center and individual research projects) will have primary responsibility for:

  • Overseeing the budget and activities of the award, as detailed.
  • Cooperating with other Consortium investigators and partners and NCI Staff, as appropriate, in the design and conduct of protocols, analysis of data, and reporting of results of research undertaken by the Consortium. This includes, but is not limited to:
    • Providing goals and estimated costs for procedures and protocols
    • Sharing data, protocols and other research resources generated through the award
    • Promoting and coordinating cross-Consortium scientific collaboration
    • Ensuring training of study site personnel as needed for standardization of collaborative protocols across sites and for accurate and timely data entry
    • Facilitating the formation of and participating in appropriate Work Groups to promote the exchange of preliminary findings, experiences, protocols, and ideas across the Consortium
    • Interacting and complying with requests for information from the Steering Committee and other sub-committees as appropriate
    • Participating in the annual PD/PI scientific/business meetings, and monthly committee calls organized by the Coordination Center, as relevant
    • Contributing to the planning and agenda of annual scientific meeting
    • Cooperating in the program evaluation activities, as needed
    • Accepting and implementing all scientific, practical, and policy decisions approved by the Steering Committee to the extent consistent with applicable grant regulations
    • Serving on the Steering Committee (for details, see "Areas of Joint Responsibility" below)
    • Providing information to the NCI Program Directors and Project Collaborators concerning progress by submitting annual progress reports in a standard format
    • Complying with federal regulatory requirements, including but not limited to those relating to human subjects protections, informed consent, and reporting of adverse events

The Consortium will be subject to periodic internal evaluation (coordinated by the Coordinating Center). All Consortium's award recipients will be expected to participate in such evaluations.

All Consortium's award recipient institutions/organizations will be expected to share with other award recipients knowledge, data, research materials, and any other resources necessary and relevant to the Consortium.

Award recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

The PD/PI(s) responsible for a research project grant will have the following additional responsibilities:

  • Determining and coordinating research approaches and procedures that can be standardized across the Consortium, and overseeing the analyses and interpretation of such research
  • Encouraging, participating, and coordinating cross-Consortium collaborations to test novel hypotheses in a complementary fashion across multiple research project grants as recommended by the Steering Committee
  • Overseeing the timely release of data according to approved plans
  • Complying with Coordinating Center requests, as directed by NCI Program Staff and the Steering Committee, to facilitate monitoring of progress

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

One or more NCI Program Directors will be substantially involved in the Consortium as NCI Project Scientists/Collaborators. NCI Project Scientists/Collaborators will have substantial scientific and programmatic involvement that is above and beyond the normal stewardship role in awards.

NCI Project Scientist/Collaborator(s) will have the following responsibilities to all Consortium award recipients:

  • Have substantial involvement to guide, coordinate, and participate in the conduct of the Consortium activities;
  • Attend and participate in all Steering Committee and subcommittee meetings of the Consortium;
  • Coordinate and facilitate the interactions among the award recipients under the cooperative agreements;
  • Serve as a liaison between the Steering Committee, the Consortium, the NIH/NCI and other federal agencies as needed;
  • Monitor the operations of the Coordinating Center and individual research projects, review their progress and compliance with the operating policies of the Steering Committee, and make recommendations on overall project directions and allocations of project funds;
  • Facilitate and coordinate the exchange of information and interactions between Consortium award recipients to support collaborative efforts;
  • Participate in organizing and coordinating annual scientific/business investigator meeting and/or other meetings identified at post-award as coordinated by the Coordinating Center;
  • Advise on the design of research activities, availability of resources, and/or management and technical performance of projects, as appropriate;
  • Participate as collaborators to the investigators in some shared activities, if appropriate;
  • Assist in avoiding unwarranted duplications of effort across the Consortium;
  • Provide oversight in the evaluation of the Consortium as coordinated by the Coordinating Center;
  • Monitor progress of the projects towards meeting milestones and adherence to the strategic goals of the program;
  • Facilitate collaborative research efforts and related activities that can involve award recipient as well as investigators from other NCI-related initiatives;
  • Evaluate the adherence of award recipients to any approved data sharing plans or intellectual property plans.

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. The NCI reserves the right to adjust funding, withhold, suspend, or terminate the support to those awardee institutions that are unable to meet the performance requirements set forth in these Terms and Conditions of Award, or significantly change the level of performance. The NCI Program Official will be responsible for monitoring the level of performance and making recommendations for any corrective actions.

Areas of Joint Responsibility include:

A Steering Committee will serve as the governing board for the Consortium. The Steering Committee will have primary responsibility for:

  • Overseeing the overall organization of the Consortium initiative and for reviewing its research goals.
  • Monitoring transdisciplinary progress of the Consortium.
  • Establishing advisory committees and subcommittees, as necessary, to serve the Steering Committee and the award recipients.
  • Establishing topical Work Groups for specific purposes, as needed, and developing the appropriate structure to promote the exchange of experiences, protocols, novel research findings, etc. across the Consortium.The NCI Program Staff will serve on such sub-committees, as they deem appropriate and/or designate an NCI representative.
  • Reviewing the potential for sharing resources located at individual research project sites to serve the needs of other projects or the entire initiative.
  • Making recommendations for re-directing the Consortium's focus in order to accommodate new scientific opportunities and directions and maximize the transdisciplinary nature of the Consortium.
  • Sharing and reviewing annual progress among the projects of the Program.

The Steering Committee will be comprised of the following voting and non-voting members:

  • The PD(s)/PI(s) of the Coordinating Center (RFA-CA-21-022), who will have one vote.
  • A research investigator of each individual research projects (RFA-CA-21-021), who will have one vote. Award recipientswardees with MPIs must designate a PI as the representing voting member. The non-voting PI of the MPI award may participate in all Steering Committee meetings. The MPIs may alternate role as voting member of the Steering Committee during the lifecycle of the award.
  • Designated NCI Project scientist/collaborator(s) representing the NCI management group, who will have up to two votes.
  • Other NCI program staff as part of the NCI management group may participate in Steering Committee meetings as non-voting members.
  • Ad-hoc members may participate in Steering Committee meetings as non-voting members.
  • Each entity must also designate a stand-by should the voting member is absent or unable to serve.

Other relevant details, including:

  • The PD(s)/PI(s) for each research project grant award and the Coordinating Center will agree to serve at least one 2-year term within the project period.
  • Steering Committee representatives from each project will be elected at the initial kick-off Consortium meeting and should reflect a balance between research investigators and disciplines.
  • The Steering Committee will meet virtually or in person once every year, at a geographical location recommended by the Steering Committee in consultation with the NCI. Award recipients are encouraged to host at least one annual meeting.
  • A Steering Committee Chair will be elected every twelve months from amongst the Steering Committee members by the committee. An individual may continue serving as Chair for more than one year if all committee members agree. NCI staff cannot serve as Steering Committee Chair.
  • In the event that PD(s)/PI(s) cannot agree on critical aspects of the Consortium, such as common protocols, then the Steering Committee, in consultation with NCI Program Staff, will vote on a recommendation for how to proceed. NCI Program Staff will have final authority to implement proposed recommendations. All activities must comply with NIH, DHHS, and Federal Guidelines.
  • Other guidelines for the Steering Committee, such as a quorum and frequency and type of meetings (in-person, remote), will be determined at its initial meeting. It is anticipated that the Steering Committee will meet at least once per month by teleconference.
  • The Steering Committee may establish an External Advisory Board, comprised of scientific experts from outside the Metabolic Dysregulation and Cancer Initiative, to serve the NIH staff, the Steering Committee and the awardees.

Cross-consortium Activities:

To facilitate synergy within the Consortium to achieve unmet scientific priorities of the Metabolic Dysregulation and Cancer Risk Program, award recipients are required to participate in cross-Consortium activities and identified pilot projects as recommended by the Steering Committee. The cross-Consortium collaborative activities will be developed and conducted by awardees at post-award as part of the Collaboration Core coordinated by the Coordinating Center. Funding for the cross-Consortium activities will be supported in part by restricted Collaborative Funds (See Section I.1 Cross-consoritium Activities and Section IV.2 R&R and Budget).

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NCI may be brought to Dispute Resolution. The Dispute Resolution Panel will have three members: one NCI designee and two designees with expertise in the relevant area, chosen by the Steering Committee. 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 agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: 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)

For general inquiries about the FOA and questions related to epidemiology:

Tram Kim Lam, PhD, MPH
Division of Cancer Control and Population Sciences (NCI)
Telephone: 240-276-6967
Email: lamt@mail.nih.gov

For inquiries related to cancer biology:

Phillip J. Daschner, MScPhD
Division of Cancer Biology (NCI)
Telephone: 240-276-6227
Email: daschnep@mail.nih.gov

For inquiries related to cancer prevention:

Edward R. Sauter, MD, PhD
Division of Cancer Prevention (NCI)
Telephone: 240-276-7657
Email: edward.sauter@mail.nih.gov

For inquiries related to cancer disparities:

Mary Ann Van Duyn, PhD
Center for Reduce Cancer and Health Disparities (NCI)
Telephone: 240-276-6165
Email: vanduynm@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)

Dawn Mitchum
National Cancer Institute (NCI)
Telephone: 240-276-5699
Email: dm437a@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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