Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
National Institutes of Health (NIH)
National Cancer Institute (NCI)
U01 Research Project Cooperative Agreements
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.
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).
Not Applicable
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.
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
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:
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 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:
Specifically, proposed research projects may seek to understand and/or address the following components:
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:
Etiology/Epidemiology-related:
Intervention-related:
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:
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.
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.
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.
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.
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.
Optional: Accepting applications that either propose or do not propose clinical trial(s).
Need help determining whether you are doing a clinical trial?
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.
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.
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.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Other
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.
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.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
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:
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.
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:
The letter of intent should be sent to:
Tram Kim Lam, PhD, MPH
National Cancer Institute (NCI)
Telephone: 240-276-6967
Email: [email protected]
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
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.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims: 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.
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:
Sub-section B. Preliminary Data
Sub-section C. Approach
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:
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:
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit 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.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
Only the review criteria described below will be considered in the review process. 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.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? Is 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?
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.
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?
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?
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?
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?
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.
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
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.
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.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the 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).
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.
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:
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:
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:
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:
The Steering Committee will be comprised of the following voting and non-voting members:
Other relevant details, including:
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.
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]
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: [email protected]
For inquiries related to cancer biology:
Phillip J. Daschner, MScPhD
Division of Cancer Biology (NCI)
Telephone: 240-276-6227
Email: [email protected]
For inquiries related to cancer prevention:
Edward R. Sauter, MD, PhD
Division of Cancer Prevention (NCI)
Telephone: 240-276-7657
Email: [email protected]
For inquiries related to cancer disparities:
Mary Ann Van Duyn, PhD
Center for Reduce Cancer and Health Disparities (NCI)
Telephone: 240-276-6165
Email: [email protected]
Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]
Dawn Mitchum
National Cancer Institute (NCI)
Telephone: 240-276-5699
Email: [email protected]
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.