Integration of Imaging and Fluid-Based Tumor Monitoring in Cancer Therapy (Clinical Trial Optional)

Integration of Imaging and Fluid-Based Tumor Monitoring in Cancer Therapy (Clinical Trial Optional) is sponsored by National Cancer Institute (NCI). This opportunity focuses on research integrating imaging techniques and fluid-based biomarkers for monitoring tumors during cancer therapy.

PAR-25-175: Integration of Imaging and Fluid-Based Tumor Monitoring in Cancer Therapy (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 Integration of Imaging and Fluid-Based Tumor Monitoring in Cancer Therapy (R01 Clinical Trial Optional) R01 Research Project Grant January 28, 2026 - NIH Removing AIDS Application Due Dates from NOFOs. See Notice NOT-OD-26-029 .

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 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 R01 grant applications describing projects that integrate imaging and fluid-based tumor monitoring (liquid biopsy) assays during cancer therapy in patients to determine the optimal use of these modalities in the characterization of therapy response and/or emergence of treatment resistance.

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 The purpose of this initiative is to support study design and integration of imaging and fluid-based tumor monitoring analyses into one or more therapeutic settings for assessing treatment success, failure or recurrence.

The knowledge gained from this initiative is expected to capture dynamic changes and clinically meaningful indices that contribute to conventional clinical and pathologic information.

The long-term goal for research supported through this NOFO will focus on determination of the precise use of imaging and fluid-based tumor monitoring assay combinations during cancer therapy to accurately monitor treatment response and emergence of resistance. Precision medicine aims to tailor specific treatment to each specific individual with the ultimate goal of improving patient outcomes.

Imaging procedures play a critical role in monitoring cancer diagnosis and treatment. Monitoring tumor molecular and genetic evolution during active treatment is believed to be beneficial in predicting metastatic potential, response, and treatment resistance.

Although emerging molecular and functional imaging techniques now enable tumor characterization at the cellular and molecular levels, obtaining multigenetic profiling to select appropriate targeted therapies still requires tumor tissue acquisition.

Liquid biopsy has emerged as a breakthrough molecular diagnostic platform with a demonstrated capability for cancer detection and diagnosis and most importantly, for prediction of treatment response. Like imaging, liquid biopsy is minimally invasive and lends itself to serial assessments.

However, the sensitivity and specificity of the two modalities in tumor detection often vary depending on tumor location, size, types and treatment settings. Therefore, combination of these two tumor monitoring modalities could be complementary, leading to more accurate monitoring and prediction of tumor treatment response.

In cancer treatments of the near future, oncologists will likely move towards monitoring response to therapy with a specific combination of fluid-based (liquid biopsy) and molecular or functional imaging tumor monitoring assays to achieve accurate and rapid assessments of tumor treatment response dynamics.

One of the many hurdles in achieving this vision is to understand how a specific fluid-based tumor monitoring assay may complement and enhance a specific imaging assay, or vice versa, in cancer detection, characterization and monitoring of treatment response across the treatment duration. The sciences of fluid-based tumor monitoring and molecular and functional imaging continue to move forward but in parallel.

Advancing their complementarity and synergy and demonstrating utility with added value of these combinations in patient care will require an integrated approach and concerted efforts across disciplines.

This NOFO is intended to promote collaboration among imaging scientists, fluid-based assay developers and clinical scientists to conduct integrated studies to determine the most appropriate use of imaging and liquid biopsy assays to accurately monitor patient disease and response to therapy during cancer treatment.

The precise application of this combination will lead to more accurate determination of therapeutic strategy and identification of the emergence of treatment resistance at the earliest time point. The specific combination of assays will be dependent on the molecular characteristics of the cancer and the assay detection limits.

The goal can be met by a research strategy where liquid biopsy biomarkers that have already entered clinical practice are combined with experimental imaging methods, or conversely, where established clinical imaging methods are combined with experimental liquid biopsy biomarkers.

Importantly, the chosen experimental liquid biopsy and imaging methods must already be developed and validated (e.g., performed on a pre-existing set of human biospecimens with the same disease or condition as that in the proposed validation application) or in final validation (e.g., in any phase of a human clinical trial) that support their clinical utility in diagnosis, prognosis, monitoring, and/or prediction of response to treatment.

For this initiative, imaging is defined as any in vivo molecular or functional clinical imaging modality. Fluid-based tumor monitoring (liquid biopsy) assay is defined as detection, quantification and characterization of molecular or cellular indicators (e.g., circulating tumor cells, circulating tumor DNA, circulating RNA, exosomes etc) in body fluids, such as blood, CSF, saliva or urine.

This NOFO will support clinical studies that propose to include tissue-based assessment for the purpose of establishing correlation to the imaging and liquid biopsy findings. Funding will support the integration and analysis of imaging and fluid-based tumor monitoring (liquid biopsy) assays into one or more therapeutic settings.

Refer to Research Strategy section listed in Section IV Application Submission and Information for specific instructions in designing and implementing clinical projects that are scientifically rigorous .

Appropriate cancer treatment settings include: Clinical trials in which patients are undergoing active treatment for the first recurrence of a cancer with effective second-line treatments and are being monitorred for treatment success, failure, or recurrence; First-line therapy with aggressive or advanced disease; Retrospective data collection and analysis from studies currently using imaging and fluid-based treatment response monitoring; Applicants are strongly encouraged to contact the Scientific/Research contacts listed in Section VII to discuss the relevance of the proposed studies before submitting the application.

RESEARCH AREAS OF INTERESTS TO THIS NOFO INCLUDE BUT ARE NOT LIMITED TO THE FOLLOWING: Examples of questions in important areas of investigation included in this NOFO include, but are not limited to the following: How do imaging and liquid biopsy based tumor monitoring results correlate within each cancer type prior to, during therapy or after treatment?

What is the minimal liquid biopsy-based monitoring change corresponding with a detectable change in tumor using imaging during treatment and vice versa? Are there specific combinations of liquid biopsy and imaging approaches for distinct cancer therapy types? Are there circumstances where a combination of imaging and liquid biopsy based tumor monitoring assay results is more powerful than either assay alone?

Are there cancer types where tumor response or emergence of resistance is detectable by imaging earlier than liquid biopsy based tumor monitoring and vice versa? Are there times when routine imaging surveillance in the patients without evidence of molecular residual disease can be substituted with serial monitoring by using liquid biopsy?

Is there evidence for circumstances where abnormal results on liquid biopsy might be used to prompt imaging assessment?

NON-RESPONSIVE APPLICATIONS Applications with the following attributes will be deemed non-responsive and will not be reviewed: Long-term post-treatment surveillance in patients where treatment has been curative; Early detection in screening setting; Pre-clinical development and testing of imaging agents/modalities or fluid-based tumor monitoring (liquid biopsy) assays; and Development of novel imaging or liquid biopsy methods or platforms; 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.

Application budgets are limited to less than $500,000 in direct costs per year and the requested amount in any year needs to reflect the actual needs of the proposed project. 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: Research Strategy.

In this section of the application, the applicants must address each of the following points: Justify the choice of patient population; Provide evidence that the necessary clinical trial and patient population will be available to the investigators; Provide the organizational structure of and communication plans for the study if it involves multiple sites and/or a separate data coordinating center; Demonstrate FDA IND/IDE (if applicable) for imaging methods or agents and fluid-based tumor monitoring assays; Provide evidence that the clinical trial data will be able to be completed in the 5-year funding time frame; Provide rigorous statistical and power analyses to assure that the integration of imaging and fluid-based tumor monitoring results will be clinically meaningful.

Letter of Support: Letters of support from clinical partners, research collaborators, or other groups the investigators propose to work with should be included. 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 components of participating organizations, NIH. Applications that are incomplete, 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. 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. Evaluate to what extent the study population and cancer treatment are appropriate and justified.

Evaluate the evidence provided by the applicant that the necessary clinical trial and/or patient population will be available to the investigators and, if relevant, that the clinical trial will be able to be completed in the 5-year funding time frame? If relevant, evaluate whether applicants demonstrated FDA IND/IDE status of imaging methods or agents and fluid-based tumor monitoring assays?

Assess to what extent the applicants state the strengths and weaknesses of integrating imaging and liquid biopsy biomarker(s) research strategy in terms of added value in risk assessment and clinical management decisions during treatment monitoring process? Evaluate whether the applicants provided statistical rationale that the integration of imaging and fluid-based tumor monitoring results will be clinically meaningful?

For studies involving genetic/genomic or multi-omics analyses, evaluate whether the plan for biospecimen analysis appropriate and justified? 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 the proposed work.

For Multiple Principal Investigator (MPI) applications, assess the quality of the leadership plan to facilitate coordination and collaboration. Evaluate whether the institutional resources are appropriate to ensure the successful execution of the proposed work.

Additional Review Criteria As applicable for the project proposed, reviewers will consider the following additional items while determining scientific and technical merit, but will not give criterion scores for these items, and should consider them in providing an overall impact score.

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, 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, evaluate: 1)