Department of Health
and Human Services (HHS)
and Human Services (HHS)
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Reissue of PAR-18-317
See Notices of Special Interest associated with this funding opportunity
PAR-20-314 - Assay Validation of High Quality Markers for Clinical Studies in Cancer (UH3 Clinical Trials Not Allowed)
93.394
Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) invites applications to support the validation of molecular/cellular/imaging markers (referred to as "markers" or "biomarkers") and assays for cancer detection, diagnosis, prognosis, monitoring, and prediction of response or resistance to treatment, as well as markers for cancer prevention and control. This FOA will support investigator-initiated research for both analytical, and clinical validation of assays to be used in cancer treatment, control, or prevention trials supported by the NCI. This FOA will also support the validation of pharmacodynamic markers and markers of toxicity. Applicants should have assays that work on human samples and whose importance is well justified for development into clinical assays. As chemotherapies and/or radiation therapies are increasingly combined with immunotherapies to enhance durability of anti-cancer responses, assays for measuring multiple markers, including immune markers, can be developed and validated simultaneously.
The UH2 phase of this FOA supports analytical validation of assays for these molecular/cellular/imaging markers, which must be achieved within 2 years before assays may undergo clinical validation. The UH3 phase of this FOA supports clinical validation of analytically validated assays for up to 3 years using well-annotated biospecimens from retrospective or prospective clinical trials or studies.
This FOA may be used to validate existing assays for use in other cancer clinical trials, observational studies, or population studies. Efforts to harmonize clinical laboratory tests, including investigation into the performance and reproducibility of assays across multiple clinical laboratories, are also appropriate for this funding opportunity. Projects proposed for this FOA will require multi-disciplinary interaction and collaboration among scientific investigators, oncologists, statisticians, and clinical laboratory scientists. This FOA is not intended to support early-stage development of technology or the conduct of clinical trials but is intended for validation of assays to the point where they could be integrated into clinical trials/studies as investigational assays. Investigators responding to this FOA must address both UH2 and UH3 phases. Milestones to be accomplished in the UH2 phase for transition to the UH3 phase must be proposed by the investigators.
Not Applicable
February 18, 2021; July 9, 2021; October 8, 2021; February 14, 2022; July 11, 2022; October 11, 2022; February 14, 2023; July 10, 2023; October 10, 2023
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.
Not Applicable
July 2021; November 2021; February 2022; July 2022; November 2022; February 2023; July 2023; November 2023; February 2024
October 2021; January 2022; May 2022; October 2022; January 2023; May 2023; October 2023; January 2024; May 2024
December 2021; February 2022; June 2022; December 2022; February 2023; June 2023; December 2023; February 2024; June 2024
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.
Purpose
Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) invites applications to further optimize and validate molecular/cellular/imaging markers (referred to as "markers" or "biomarkers") and assays for cancer detection, diagnosis, prognosis, monitoring, and prediction of response or resistance to treatment, as well as markers for cancer prevention and control. This FOA will support investigator-initiated research for both analytical, and clinical validation of assays to be used in cancer treatment, control, or prevention trials supported by the NCI. This FOA will also support the validation of pharmacodynamic markers and markers of toxicity. Applicants should have assays that work on human samples and whose importance is well justified for development into clinical assays. As chemotherapies and/or radiation therapies are increasingly combined with immunotherapies to enhance the durability of anti-cancer responses, assays for measuring multiple markers, including immune markers, can be developed and validated simultaneously.
The UH2 phase of this FOA supports analytical validation of assays for these molecular/cellular/imaging markers, which must be achieved within 2 years before assays may undergo clinical validation. The UH3 phase of this FOA supports clinical validation of established assays for up to 3 years using specimens from retrospective or prospective clinical trials/studies. This FOA may be used to validate existing assays for use in other cancer clinical trials, observational studies, or population studies. Efforts to harmonize clinical laboratory tests, including investigation into the performance and reproducibility of assays across multiple clinical laboratories, are also appropriate for this FOA. Projects proposed for this FOA will require multi-disciplinary interaction and collaboration among scientific investigators, oncologists, statisticians, and clinical laboratory scientists. This FOA is not intended for early-stage development of technology or to support clinical trials but is intended for analytical and clinical validation of assays to the point where they could be integrated into clinical trials/studies as investigational assays. Investigators responding to this FOA must address both UH2 and UH3 phases. Milestones to be accomplished in the UH2 phase for the transition to the UH3 phase must be proposed by the investigators.
Background
NCI-supported clinical trials, as well as prevention or cancer control studies, increasingly depend upon essential or integral marker-based assays for eligibility, stratification, disease monitoring, or primary study endpoints. These markers and assays may be for pharmacodynamic, mechanism of action, prognostic, predictive, and/or for treatment response. They may also be related to the risk of cancer in prevention or cancer control studies. Many of these assays are proposed by investigators in academic laboratories or small biotechnical companies that have developed interesting markers based on discovery research. Most investigators are generally comfortable developing assays based on discovered markers for research purposes but may not have the expertise and support for developing validated assays for clinical purposes as well as for navigating the regulatory requirements that clinical laboratory assays must meet. This can cause considerable delay and added expense to successfully conducting clinical trials. This FOA uses a cooperative agreement that enables NCI staff to proactively assist investigators to meet the requirements for analytical and clinical validation of assays and prepare the assays for their use in clinical trials/studies.
Research objectives
Applications in response to this FOA must propose to optimize an existing assay(s) using human specimens in a clinical laboratory into assays that can be used in a clinical trial/study for the treatment, prevention or control of cancer. However, efforts to harmonize clinical laboratory tests, including investigation into the performance and reproducibility of assays across multiple clinical laboratories, are also appropriate for this funding opportunity.
The primary elements for achieving the research objectives are as follows:
Project characteristics
Assay pre-requisites and preliminary data
The applicant must have a working assay(s) using human specimens. The assays may be derived from marker discovery research or result from previous hypothesis-driven clinical studies. The assay(s) may be a multiplex assay or a classifier but must, after conversion to a clinical assay, be suitable for performing in a clinical trial/study. Preliminary data should define the current status of the assays as well as justify support for optimization and usability in a clinical trial/study.
UH2/UH3 mechanism
The UH2/UH3 mechanism has two phases. The initial cooperative agreement awards will be granted for up to 2 years for analytical validation of the assays in the UH2 phase. If the project meets the metrics described for the UH2 phase, then the project will proceed to the UH3 phase pending review and availability of funds as described below.
UH2 Phase
Objectives for the UH2 phase (analytical validation phase)
During the UH2 phase, the investigators must complete the analytical validation of their assays. Since this is not likely to require large numbers of samples, the investigators are expected to have access to samples that are appropriate for the clinical context of the intended use of the assays. Attention needs to be paid to pre-analytic variables and their effect on marker stability within biospecimens appropriate for the clinical context of use.
The UH2 Analytical Validation phase should determine the following (but not be limited to) performance characteristics of the assay required for the successful conduct of the study proposed for the UH3 award:
Investigators with assays that have already met the above criteria for analytical validation may apply directly for the UH3 phase funding of the clinical validation of assays through the companion FOA (PAR-20-314).
Minimum criteria for transition from UH2 to UH3
After administrative review by NCI program staff, successful UH2 projects will be prioritized for selection and transition to the UH3 phase.
UH3 Phase
Objectives for the UH3 phase (clinical validation phase)
The UH3 phase will support the clinical validation of the markers/assays and prepare them for use in a clinical trial/study.
Expected outcomes of the UH3 phase that should be met by each project
The UH3 project should demonstrate the association of the result of the assays with a clinical endpoint (e.g., survival, response, disease presence or absence) in samples from patients that have been treated or exposed to a uniform intervention or observation in treatment, prevention or cancer control studies, for example:
Applications Not Responsive to 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.
Need help determining whether you are doing a clinical trial?
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Applicants may request up to $275,000 direct costs for the entire UH2 phase with no more than $200,000 requested in any one year and up to $250,000 direct costs for the UH3 phase per year.
The proposed project period for the initial development phase (UH2) must not exceed 2 years (but may be shorter). The proposed project period for the second validation phase (UH3) must not exceed 3 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 not 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.
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.
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
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.
The Investigative Team should include:
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.
Other Plan(s):
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
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.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims
Provide the overall goals for the entire application and indicate separately Specific Aims to be accomplished in the UH2 phase and in the UH3 phase.
Research Strategy
Applicants should organize the Research Strategy into the sub-sections 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 (may be divided into two parts corresponding to the UH2 and UH3 phases)
UH2 Analytical Validation Phase should address each of the items listed below:
UH3 Clinical Validation Phase should describe the plan for clinical validation of the assays within the intended clinical context of use and should address each of the items below:
Sub-Section D. Milestones and Timeline
A timeline (Gantt chart) including milestones is required. Milestones are goals that create go/no-go decision points in the project and must include clear and quantitative objective criteria for success. Milestones must consist of appropriate objective performance targets such as a required limit of detection and coefficient of variation, or sensitivity and specificity. Yearly quantitative milestones are required to provide clear indicators of a project's continued progress or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years. The application must include well-defined milestones and timelines for assessing progress in both the UH2 and UH3 phases, including specific milestones for progressing from the UH2 phase to the UH3 phase.
Milestones and timelines for each UH2 and UH3 stage must be provided in a separate heading at the end of the Approach section and should:
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:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
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.
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 NCI, 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.
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
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 this particular announcement, note the following:
This FOA is focused on the validation of assays that will be used in clinical trials or studies on cancer treatment, prevention or cancer control. Therefore, the potential of the proposed project to validate or harmonize such assays and markers for a specific cancer-related clinical context is essential and will be a main factor in assessing the overall merit of the applications.
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.
Significance
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Specific for this FOA
How well do the proposed marker(s) and assay(s) address an important cancer problem that is significant within the clinical context? What is the potential of the proposed assays to be broadly adopted by the healthcare community for use in treatment, prevention or cancer control?
Investigator(s)
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Specific for this FOA
Please comment on the appropriateness of the team expertise to manage the validation of the assay(s) within the specified clinical context of use. How well will the team be able to manage the further development of the assay(s) should it be successful so that it can be distributed and ultimately available to the healthcare community?
Innovation
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Specific for this FOA
If the markers are already established in practice, how well do the investigators propose to develop the assays for a novel clinical context of use? Although innovation criteria in a traditional sense may not apply for projects involving harmonization studies, have the investigators provided sufficient justification for the critical need for harmonization and identified steps in assay procedures (new technology, new reference standards) that would enable success in harmonization efforts?
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 for this FOA
How well considered is the plan to validate or to harmonize the clinical marker(s) and assay(s)? Is the analytical validation in the UH2 phase appropriate, with sufficient attention paid to pre-analytic variables for stabilizing the analytes (markers)? Does the plan for clinical validation of the assays in the UH3 phase include an appropriate number of specimens for associating assay results with a pre-specified clinical endpoint, justified by a statistical plan? Does the project include a plan for assay distribution to assure its availability for the healthcare community? Are the milestones clearly specified for transitioning from the UH2 to the UH3 phase? Do the milestones provide quantitative metrics? Do the milestones deal with assay performance characteristics that are pertinent to the intended use of the assays?
Environment
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
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.
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
For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.
Renewals
Not Applicable
Revisions
Not Applicable
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
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 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.
Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate National Cancer Advisory Board. The following will be considered in making funding decisions:
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that 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.
After administrative review by NCI program staff, successful UH2 projects will be prioritized for selection and transition to the UH3 phase.
Criteria used to evaluate such transition will include:
Successful achievement of the milestones for analytical validation;
Clear delineation of the intended use of the assays in a clinical trial/study;
Potential for completing clinical validation of the assays within its intended clinical use including access to appropriate specimens from prior trials/studies, statistical power analysis based on the analytical performance of the assays, plans for IRB approval;
Availability of funds;
NCI program priorities.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights 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) 2 CFR Part 200 Administrative Regulations, 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 awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility reside 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 the primary responsibility for:
Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
NCI Program staff member(s) acting as a Project Scientist(s) will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. Additional NCI staff members may be designated to have substantial involvement. The NCI Project Scientist(s) and any other substantially involved staff members will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications. If such participation is deemed essential, these individuals will seek NCI waivers according to the NCI procedures for the management of conflict of interest.
The main activities of the NCI substantially involved staff members include but are not limited to the following aspects:
Additionally, an NCI Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.
NCI reserves the right to terminate or curtail any individual award, including the UH3 phase if there is insufficient progress towards meeting milestones.
Areas of Joint Responsibility include:
Steering Committee:
The Program Steering Committee will serve as a non-voting organizational body for the NCI and awardees. The Program Steering Committee will consist of:
Two representatives of each awardee (the contact PD/PI and designated backup senior investigator); and
Two NCI Project Scientists.
The Program Steering Committee will be organized and administratively managed by the NCI staff.
The members of the Steering Committee will meet once a year in person with required awardee attendance and by conference calls as needed.
The Steering Committee will be responsible for the following:
Dispute Resolution:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
Data Management and Sharing
Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.
Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.
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: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-637-3015
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov
For inquires related to response, resistance, and risk stratification markers for treatment trials, please contact:
Tracy G. Lively, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5944
Email: livelyt@mail.nih.gov
Sumana Dey, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5748
Email: sumana.dey@nih.gov
For inquires related to companion diagnostics and pharmacodynamic and safety markers for treatment trials, please contact:
Minkyung (Min) Song, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276- 6139
Email: songm@mail.nih.gov
For inquires related to assays involving screening and early detection:
Lynn Sorbara, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-7135
Email: lynns@mail.nih.gov
For inquires related to assays involving cancer epidemiology and population science:
Rao Divi, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6913
Email: divir@mail.nih.gov
For inquires related to assays involving cancer epidemiology and population science:
Mukesh Verma, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276- 6889
Email: vermam@mail.nih.gov
Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: ncirefof@dea.nci.nih.gov
Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: Woodwars@mail.nih.gov
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.
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