Mechanisms that Impact Cancer Risk after Bariatric Surgery (R01 Clinical Trial Optional)

Mechanisms that Impact Cancer Risk after Bariatric Surgery (R01 Clinical Trial Optional) is sponsored by National Institutes of Health (NIH). Supports research on mechanisms impacting cancer risk post-bariatric surgery.

PAR-25-043: Mechanisms that Impact Cancer Risk after Bariatric Surgery (R01 Clinical Trial Optional) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. 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 Mechanisms that Impact Cancer Risk after Bariatric Surgery (R01 Clinical Trial Optional) R01 Research Project Grant Notices of Special Interest associated with this funding opportunity March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 .

August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy.

See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity Exploratory/Developmental Grants See Section III. 3.

Additional Information on Eligibility .

Assistance Listing Number(s) Funding Opportunity Purpose Through this Notice of Funding Opportunity (NOFO), the National Cancer Institute (NCI) invites applications for support of investigator-initiated studies addressing mechanisms by which bariatric surgery impacts cancer risk and seeks to draw in talented scientists who study bariatric surgery to investigate its effects on cancer, rather than shorter term outcomes such as weight loss and diabetes.

Open Date (Earliest Submission Date) The following table includes NIH standard due dates marked with an asterisk. Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed All applications are due by 5:00 PM local time of applicant organization.

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

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the NOFO) 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.

Use the NIH ASSIST system to prepare, submit and track your application online. 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. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II.

Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V.

Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII.

Other Information Part 2. Full Text of Announcement Section I.

Notice of Funding Opportunity Description Through this Notice of Funding Opportunity (NOFO), the National Cancer Institute (NCI) invites applications for support of investigator-initiated studies addressing mechanisms by which bariatric surgery impacts cancer risk and seeks to draw in talented scientists who study bariatric surgery to investigate its effects on cancer, rather than shorter-term outcomes such as weight loss and diabetes.

Obesity: Obesity will soon surpass smoking tobacco as the number one cause of preventable death both in the United States and worldwide. Bariatric (metabolic) surgery is the most effective strategy to achieve significant initial and sustained weight loss among individuals who are morbidly obese.

Bariatric surgery provides dramatic improvement in metabolic function, associated with a reduction in type 2 diabetes mellitus (T2DM) and cardiovascular (CV) risk. Bariatric surgery also appears to reduce the risk of certain obesity-related cancers, although which cancers are favorably impacted vary by study, and the mechanism(s) driving this risk reduction is mostly speculative.

Bariatric surgery is performed in over 250,000 people in the U.S. annually, and the frequency is rising. Studies evaluating which bariatric surgery procedure(s) are most effective in cancer risk reduction could help bring to light new pathways to target for cancer prevention.

Bariatric Surgery: Importantly, it is not yet clear from clinical and preclinical studies if the benefit from bariatric surgery arises from weight loss alone or if there is also a surgery-specific benefit.

One mechanism for a possible surgery-specific effect is elevated bile acids (BA), both intestinal and circulating, after gastric bypass surgery such as Roux-en-Y gastric bypass (RYGB) that are proposed to be central to weight loss and other metabolic benefits. The interaction between BA and intestinal microbes is also an area of intense interest.

Studies have identified important changes after bariatric surgery in the composition and function of the gut microbiome, which may mediate bariatric surgery effects. Fecal microbiota transplantation (FMT) from humans or mice that had undergone bariatric surgery to germ-free recipient mice showed decreased weight gain and decreased adiposity are both transmissible traits.

In addition, FMT induced important host metabolic changes including decreased energy harvest from the diet, increased resting energy expenditure, and increased lipid utilization. The data suggest a causal link between gut microbiota and the metabolic and weight loss effects of bariatric surgery.

If validated, the findings will provide insight into the mechanisms driving the benefit of bariatric surgery on cancer risk and would be useful to further scientific understanding and patient care.

Animal Models: Several diets or genetically induced animal models of obesity have consistently demonstrated the benefits of weight loss on cancer risk, and these obesity-induced tumor models may be adaptable to bariatric surgery studies, such as the Kras model of pancreatic cancer. Animal models have been developed to study the effects of bariatric surgery.

Rodent animal models are most often used due to feasibility (low cost, ease of housing) and have been used extensively to study the mechanism(s) of bariatric surgery responsible for the reduction or elimination of T2DM and CV risk.

However, very little has been reported on bariatric surgery and cancer risk despite the fact that both rat and murine models of mammary and other cancers develop in 6 months or less, making it feasible to assess mechanistic changes that influence cancer risk. Bariatric Surgery and Cancer Risk: Obese patients undergo bariatric surgery for a variety of reasons, including weight loss and improvement in metabolic dysfunction.

Physician advice regarding the potential benefit of bariatric surgery and cancer risk reduction can currently only be given in generalities based on large-scale studies and not targeted to the individual. Many but not all bariatric surgery investigations document an overall cancer risk reduction among women but not men.

Some but not all bariatric surgery studies have found that both women and men undergoing bariatric surgery have an increased risk of colorectal cancer (CRC). Older studies which assessed bariatric surgery and cancer risk may not be useful to guide targeted advice to patients, as one of the most common procedures performed in the past, gastric banding, is only performed in 1% of bariatric surgery procedures today.

The two most common bariatric surgery procedures currently performed are sleeve gastrectomy and RYGB. As such, planned animal and/or human studies should focus on the mechanistic effects of the two procedures that are currently in common use.

Human biospecimens and/or data may be available from cohorts to enhance the studies proposed including the Longitudinal Assessment of Bariatric Surgery (LABS), Adolescent Bariatrics: Assessing Health Benefits & Risks (Teen-LABS), and NCI Cohort Consortium Members. Applications that include collaborators from fields outside of cancer research will be given special programmatic consideration.

Responsive applications may investigate animal models, human studies, or a combination of both. General Area of Research and Scope of Work for this NOFO Examples of relevant areas of research include but are not limited to : Do alterations in cancer risk biomarkers occur before weight loss? If so, in what organ, tissue, or cell type do they originate?

Is maximum weight loss or long-term weight loss more important for cancer risk reduction? If so, how do the two differ at a cellular and/or biochemical level? What mechanism(s) explain the evidence that bariatric surgery is more beneficial in cancer risk reduction in women than men?

Does bariatric surgery increase or decrease the risk of CRC, and if so, what are the mechanism(s)? Which cancers are decreased in incidence by bariatric surgery, and what are the mechanism(s) that explain the effect? Are any cancers increased in incidence by bariatric surgery?

If so, through what mechanism(s)? Does the specific bariatric surgery procedure have an impact on cancer risk? If so, what are the mechanism(s) driving the difference in impact?

Does racial or ethnic background influence the impact of bariatric surgery on cancer risk, and if so, what are the mechanism(s) involved? How does bariatric surgery affect the penetrance of high-risk genetic predisposition to cancer? How do changes in the GI microbiome after BS affect metabolite pools and interactions with host (epithelial and immune) tissues?

Scope of Work and Additional Guidance It is anticipated that studies will evaluate bariatric surgery animal models where a significant proportion of the animals develop cancer.

Similarly, human studies involving individuals who will or have undergone bariatric surgery are also encouraged, so long as within the cohort to be studied the number of enrolled subjects who develop cancer is adequate to for a statistically powered endpoint linking cancer (and not a biomarker of cancer) to a molecular mechanism as the driver of cancer.

When appropriate and feasible, the investigators may want to evaluate mechanisms influenced by bariatric surgery in animal models of cancer and evaluate potential changes that might correlate with humans due to bariatric surgery. We define mechanism as a biologic endpoint based on analyzed samples from bariatric surgery animal models or from subjects who have or are planned to undergo bariatric surgery.

This NOFO does not support studies where an epidemiologic endpoint is the primary aim of the project. The mechanism(s) to be studied should evaluate samples collected from animals or humans who have undergone bariatric surgery who did or did not develop cancer. If both animals and humans are studied, the mechanisms chosen should be based on a cancer endpoint.

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

This NOFO is not intended for epidemiologic studies, where the primary endpoint is the assessment of cancer in a cohort of animals or humans, which has undergone bariatric surgery and mechanistic studies evaluating bodily fluid or tissue samples are nonexistent or of secondary endpoints. Applications that focus entirely on in vitro investigations. Epidemiologic investigations as the primary focus of the application.

Animal or human studies that do not evaluate tissue and/or bodily fluid samples collected from participants who have undergone bariatric surgery, some of which developed cancer after surgery. Application, which includes a clinical trial that does not have a bariatric surgeon as a key investigator on the team.

NOTE: Applicants to this NOFO are strongly encouraged to 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 clinical trial, so that NCI staff can help the applicant understand whether the proposed clinical trial is within the goals and mission of the NCI and is appropriate for this NOFO.

See Section VIII. Other Information for award authorities and regulations. Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Section II. Award Information Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types.

Only those application types listed here are allowed for this NOFO. 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 The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Budgets are limited to $500,000 direct costs per year. The scope of the proposed project should determine the project period.

The maximum project period is 5 years. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO. Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education 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 (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession 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 Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 must complete and maintain the following registrations as described in the How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications for additional information.

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually . The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM. gov registration process.

The same UEI must be used for all registrations, as well as on the grant application. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants. gov registrations; all registrations must be in place by time of submission.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants. gov – Applicants must have an active SAM registration in order to complete the Grants.

gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.

If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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 their organization to develop an application for 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 How to Apply-Application Guide. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.

3. 7. 4 Submission of Resubmission Application .

This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application. A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2. 3. 9.

4 Similar, Essentially Identical, or Identical Applications ). Section IV. Application and Submission Information 1.

Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.

gov Workspace are available in Part 1 of this NOFO. 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 How to Apply - Application Guide except where instructed in this notice of funding opportunity 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. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

All instructions in the How to Apply - Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply- Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: Resource Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions: All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan.

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

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 How to Apply- 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 How to Apply- Application Guide must be followed.

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 How to Apply- Application Guide must be followed. PHS Assignment Request Form All instructions in the How to Apply- Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM) See Part 2. 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.

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 Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications .

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 How to Apply-Application Guide. 5.

Intergovernmental Review (E. O. 12372) This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement . Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7. 9.

1 Selected Items of Cost. 7. Other Submission Requirements and Information Applications must be submitted electronically following the instructions described in the How to Apply 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. All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form . Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

See Section III of this NOFO for information on registration requirements. The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply 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 NCI. Applications that are incomplete, or non-compliant, and/or nonresponsive will not be reviewed.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200. 113 and NIH Grants Policy Statement Section 4.

1. 35 . Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected] .

Post Submission Materials Applicants are required to follow the instructions for post-submission materials, as described in the policy Section V. Application Review Information 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.

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 scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will evaluate Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate criterion score. Factor 1.

Importance of the Research (Significance and Innovation) Evaluate the importance of the proposed research in the context of current scientific challenges and opportunities, either for advancing knowledge within the field, or more broadly. Assess whether the application addresses an important gap in knowledge in the field, would solve a critical problem, or create a valuable conceptual or technical advance.

Evaluate the rationale for undertaking the study, the rigor of the scientific background for the work (e.g., prior literature and/or preliminary data) and whether the scientific background justifies the proposed study. Evaluate the extent to which innovation influences the importance of undertaking the proposed research.

Note that while technical or conceptual innovation can influence the importance of the proposed research, a project that is not applying novel concepts or approaches may be of critical importance for the field. Evaluate whether the proposed work applies novel concepts, methods or technologies or uses existing concepts, methods, technologies in novel ways, to enhance the overall impact of the project.

Specific to this NOFO: Evaluate how likely are the proposed studies to link bariatric surgery procedures to human cancer incidence and/or mortality? How well does the proposed work help in defining the mechanism by which bariatric surgery impacts cancer risk? Factor 2.

Rigor and Feasibility (Approach) Evaluate the scientific quality of the proposed work. Evaluate the likelihood that compelling, reproducible findings will result (rigor) and assess whether the proposed studies can be done well and within the timeframes proposed (feasibility). Evaluate the potential to produce unbiased, reproducible, robust data.

Evaluate the rigor of experimental design and whether appropriate controls are in place. Evaluate whether the sample size is sufficient and well-justified. Assess the quality of the plans for analysis, interpretation, and reporting of results.

Evaluate whether the investigators presented adequate plans to address relevant biological variables, such as sex or age, in the design, analysis, and reporting. For applications involving human subjects or vertebrate animals, also evaluate: the rigor of the intervention or study manipulation (if applicable to the study design). whether outcome variables are justified.

whether the results will be generalizable or, in the case of a rare disease/special group, relevant to the particular subgroup. whether the sample is appropriate and sufficiently diverse to address the proposed question(s). For applications involving human subjects, including clinical trials, assess the adequacy of inclusion plans as appropriate for the scientific goals of the research.

Considerations of appropriateness may include disease/condition/behavior incidence, prevalence, or population burden, population representation, and/or current state of the science. Evaluate whether the proposed approach is sound and achievable, including plans to address problems or new challenges that emerge in the work.

For proposed studies in which feasibility may be less certain, evaluate whether the uncertainty is balanced by the potential for major advances. For applications involving human subjects, including clinical trials, evaluate the adequacy and feasibility of the plan to recruit and retain an appropriately diverse population of participants.

Additionally, evaluate the likelihood of successfully achieving the proposed enrollment based on age, race, ethnicity, and sex. For clinical trial applications, evaluate whether the study timeline and milestones are feasible. Specific to this NOFO: Evaluate how likely is the research plan to identify, or to further our understanding of, mechanisms that drive reduction in cancer risk as a result of bariatric surgery?

How effectively does the study relate its mechanistic hypothesis or hypotheses to a cancer (in situ or invasive) endpoint rather than an intermediate endpoint of cancer? How well do the hypothesis and specific aims of the study focus on the mechanism(s) driving the effects of bariatric surgery on cancer risk?

How suitable is the investigative team’s experience or familiarity with bariatric surgery and bariatric surgery procedures for the proposed work? Factor 3. Expertise and Resources (Investigator(s) and Environment) Evaluate whether the investigator(s) have demonstrated background, training, and expertise, as appropriate for their career stage, to conduct