Part 1. Overview Information

Key Dates

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.

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.

IMPORTANT: Per NOT-OD-24-086 updated application forms (FORMS-I) will be used for this opportunity. The updated forms are not yet available and will be posted 30 calendar days or more prior to the first application due date. Once posted, you will be able to access the forms using one of the following submission options:

1. NIH ASSIST
2. An institutional system-to-system (S2S) solution
3. Grants.gov Workspace

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

Through this Notice of Funding Opportunity (NOFO), 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 NOFO 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 NOFO 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 NOFO 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 NOFO supports clinical validation of established assays for up to 3 years using specimens from retrospective or prospective clinical trials/studies. This NOFO 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 NOFO. Projects proposed for this NOFO will require multi-disciplinary interaction and collaboration among scientific investigators, oncologists, statisticians, and clinical laboratory scientists. This NOFO 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 NOFO 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 NOFO 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 NOFO 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. In the context of these NOFOs “imaging” refers to in vitro imaging modalities such as microscopy but not clinical radiology.

The primary elements for achieving the research objectives are as follows:

• Existing assay: an assay that has been reduced to practice in human tissues. The assay may be from discovery research or based on the scientific investigator's interests.
• Clinical laboratory: a laboratory that provides assay results that either assist in medical decision-making or test postulates or mechanisms of action of clinical, prevention or cancer control treatments or interventions. Assays that support medical decision-making need to be performed in CLIA-certified laboratories. Assays to test postulates or mechanisms should conform to GLP or ISO 17025 standards, in order to assure that the data generated by the assays are of sufficient quality as to be useful in clinical trials and justify sample collection.
• Markers/Biomarkers: molecular/cellular/imaging markers that are associated with a clinical endpoint in a pre-defined clinical context or situation that yields usable information about diagnosis, prognosis, or response to clinical intervention for treatment, prevention, or control of cancer. NOTE: In the context of these NOFOs "imaging" refers to in vitro imaging modalities (e.g. microscopy) not clinical radiology (e.g. PET or MRI).

Project characteristics

• The project must focus on assays whose marker or classifier is likely to be used in treatment trials, prevention studies, or cancer control studies. There does not need to be a commitment to a particular clinical trial/study.
• Awards will be based on how well the applicant justifies the use of their proposed assay(s) and marker(s) in clinical trials or clinical studies as well as the ability of the applicant's team to perform analytical and clinical validation of assays in their clinical laboratory.
• The status of the existing assays and the plan for optimization in the clinical laboratory are critically important.
• This NOFO should use technologies already in use or soon to be approved for use in clinical laboratories since this is not a technology development NOFO.
• Applications to improve standardization or harmonization of assays among laboratories for use in clinical trials/studies are appropriate for this NOFO. Clinical laboratory assays are deemed to be "harmonized" when the results are independent of the specific assay procedure/protocol and where and when the assays are performed. If a commutable reference material is available and the unit of measurement for the analyte has been standardized, the assays can be harmonized by requiring that all procedures be directly or indirectly calibrated to the primary reference material using the standardized unit of measure. Such harmonization effort would require a multicenter study to evaluate the performance of the assay protocols, including the limit of detection, limit of quantification (as applicable), linearity of the assay across the measuring range, and reproducibility (inter- and intra-assay variability).
• Metrics for analytical and clinical validation as quantitative milestones will be used to assess the potential transition from the UH2 to UH3 phase.

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:

• Accuracy;
• Precision;
• Analytical sensitivity;
• Analytical specificity, including in the presence of interfering substances;
• Reportable range of test results for the test system;
• Reference intervals (normal values) with controls and calibrators;
• Standardization of methods if the assays are to be performed in multiple laboratories;
• Establishment of appropriate quality control/assurance measures and improvement procedures;
• Any other performance characteristic required for test performance with the determination of calibration and quality control procedures.

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 NOFO (PAR-23-314).

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:

• Definition of the sensitivity and specificity of the assay results with respect to the defined clinical endpoint;
• Estimation of the prevalence of the markers within subjects or patients for the intended clinical context;
• Establishment of an appropriate cut-off or threshold for the assays using appropriate statistical analysis.

Non-responsive Applications

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. 

• Applications with the following attributes will be deemed non-responsive and will not be reviewed:
• Projects that propose to support clinical trials. This NOFO is intended to bring assays to the point where they can be integrated into future clinical trials/studies.
• Applications that propose early-stage development of technologies/assay(s).
• Applications with assays that have not been demonstrated to work on human samples and where importance is not well justified for development into clinical assays.
• Projects focused on technology development for assays or biomarker discovery such as those covered by the Innovative Molecular Analysis Technologies Program (IMAT) or the Early Detection Research Network (EDRN) at the NCI. 

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

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

1. Eligible Applicants

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized).

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

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

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.

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. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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.

2. Cost Sharing

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

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, 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.

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

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.

SF424(R&R) Cover

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.

The Investigative Team should include:

• Clinical Investigator: Investigator(s) who define the intended clinical context of use for the markers and assays and will oversee their incorporation into a potential clinical trial/study – likely to be oncologist(s) who treat patients but may be a translational scientist(s).
• Clinical Laboratory Staff: Staff who will perform the translation of the assays into clinical assays. The staff may work in a CLIA-certified clinical laboratory but do not need to do so if the assays are not intended to be used for medical decision-making. In that case, the assays are likely to be for hypothesis or mechanism of action testing and the clinical laboratory staff and their laboratory need to be aware of Good Laboratory Practices and/or ISO 17025 standards and perform to that level of quality but not necessarily be certified. In any case, the clinical laboratory staff needs to be aware of the Westgard rules. Clear involvement of clinical laboratory staff must be demonstrated in the application.
• Statistician: A statistician familiar with the needs of marker studies should be part of the team, especially for the UH3 phase when power calculations need to be provided for assessing the use of the assays and markers within the intended clinical context.
• Commercial Developer: While not necessary for all projects, successful assays will need to be distributed and supported. Plans for collaboration with a commercial partner who will support the distribution and commercialization of the assays are encouraged but not required.

R&R Budget

All instructions in the How to Apply- Application Guide must be followed.

R&R Subaward Budget

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.

PHS 398 Research Plan

All instructions in the How to Apply- 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

• Define the specific cancer-related problem to be addressed, including the markers and assays and how they fit the intended clinical context in which they will be used;
• Provide the biologic or discovery research rationale for the marker(s) and its importance;
• Outline the proposed marker(s) and assay(s), and their potential for affecting the intended clinical context in treatment trials, prevention studies or cancer control studies;
• Include the type of specimen to be used for the assays and how the assay results will be used.

Sub-Section B. Preliminary Data

• Describe the current state of development of the assays and their prospect for clinical development;
• Demonstrate the function of the assays with human specimens, including the current reagents and technologies and types of specimens that the assays will use (e.g., fresh frozen or formalin-fixed tissue, serum or plasma);
• Identify if any of the analytical validation metrics listed in Section I above as expectations for the UH2 phase have been analyzed or completed.

Sub-Section C. Approach (maybe divided into two parts corresponding to the UH2 and UH3 phases)

UH2 Analytical Validation Phase should address each of the items listed below:

• Plan to perform analytical validation of the marker(s) and assay(s) within the sample matrix of its intended use;
• Plan to obtain appropriate well-annotated human specimens for developing and optimizing the assay(s);
• Plan to evaluate the marker's (analyte's) stability within the matrix of the specimens to be used;
• Plan to evaluate (i) accuracy, (ii) precision, (iii) analytical sensitivity, (iv) analytical specificity including in the presence of interfering substances, (v) reportable range of test results for the test system, (vi) reference intervals (normal values) with controls and calibrators, (vii) harmonization of analytical performance if the assay(s) are to be performed in multiple laboratories, (viii) establishment of appropriate quality control and improvement procedures, and (ix) any other performance characteristic required for test performance in the UH3 study with determination of calibration and control procedures;
• Plan to address the regulatory issues regarding the use of the marker(s) and assay(s) in clinical trials/studies within the intended clinical context;
• Plan for the management of the intellectual property and potential collaboration with commercial entities to support the assay(s) if successful.

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:

• Definition of the clinical endpoint of interest (e.g., survival, response, disease presence or absence);
• Definition of the association(s) of interest between the assay result(s) and the clinical endpoint, such as sensitivity and specificity of the assay with respect to the clinical endpoint or prevalence of the marker within the intended study population;
• Plan to accrue specimens to perform clinical validation of assays including identification of the clinical trial/study that will provide specimens, documentation of appropriate availability and pre-approvals to get specimens (i.e. indication that the repository holder identifies availability of specimens and that there is an appropriate process to get the specimens with reasonable certainty);
• Provision of a statistical power analysis that defines the number of specimens needed;
• Plan for additional optimization such as establishing a clinical threshold or cut-off for assay(s);
• Plan to address additional regulatory requirements needed to bring assays into a clinical trial/study, including the potential requirement for an Investigational Device Exemption from the FDA.

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:

• Provide appropriately detailed (quantitative) criteria by which milestone achievement will be assessed;
• Provide a detailed timeline for the anticipated attainment of each milestone and the overall goal;
• Identify any impediments that could require an addendum to the research plan, milestones, or timeline with a discussion of alternative approaches;
• Metrics for clinical validation of the assays to be achieved during the UH3 phase.

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.

Other Plan(s): 

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.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the 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.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

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.

Important reminders:

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, 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

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

This NOFO 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 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. 

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.

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.

2. Review and Selection Process

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 NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

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

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Institutional Review Board or Independent Ethics Committee Approval: Recipient 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 recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH 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 NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 2 CFR Part 200, 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 recipients 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 recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Defining the overall research objectives and approaches of the projects;
• Determining experimental approaches, designing protocols, setting project milestones, and overseeing the conduct of experiments;
• Overseeing and coordinating the effort of the multidisciplinary teams and participating institutions and ensuring their optimal integration;
• Overseeing the conduct of UH2/UH3 research projects and ensuring their scientific rigor;
• Ensuring compliance with the applicable mandatory regulations (including protection of human subjects);
• Adhering to the NIH policies regarding intellectual property, data release, and other policies that might be established during the course of the project;
• Submitting periodic updates on human subject and accrual reports upon initiation of validation studies;
• Participating as Members of the Steering Committee;
• Participating in regular teleconferences with NCI program staff;
• Attending annual Steering Committee meetings organized by the NCI;

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

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:

• Providing input on experimental and clinical approaches, assisting in designing protocols, and consulting on updates to project milestones;
• Providing advice to the recipients on specific scientific, analytical, and clinical issues;
• Assisting and advising recipients with regard to various regulatory and compliance issues;
• Participating in regular teleconferences with PDs/PIs to monitor progress and facilitate cooperation;
• Monitoring progress of the projects towards meeting milestones and adherence to the strategic goals of the program;
• Reviewing all major transitional changes that the recipients might propose (e.g. from the UH2 to the UH3 project) and advising on their appropriateness prior to implementation to ensure consistency with the goals of this FOA;
• Tracking accrual of participants for clinical testing to ensure proper completion of this essential step;
• Participating in the activities of the Steering Committee;
• Stimulating interactions among recipients;
• Attending annual Steering Committee meetings organized by the NCI;
• Contributing to publications and presentations resulting from the project if appropriate.

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 recipients. The Program Steering Committee will consist of:

Two representatives of each recipients (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 recipients attendance and by conference calls as needed.

The Steering Committee will be responsible for the following:

• Communication and coordination among funded projects, including sharing ideas, logistics, and solutions to technical issues;
• Other shared advice may include promise of clinical potential, manufacturability, regulatory issues, and deployment into local resource-limited settings.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: 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 recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

Consistent with the 2023 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.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

For inquires related to response, resistance, and risk stratification markers for treatment trials, please contact:

Sumana Dey, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5748
Email: [email protected]

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: [email protected]

For inquires related to assays involving screening and early detection:
Lynn Sorbara, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-7135
Email: [email protected]

For inquires related to assays involving cancer epidemiology and population science:
Rao Divi, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6913
Email: [email protected]

For inquires related to assays involving cancer epidemiology and population science:
Mukesh Verma, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276- 6889
Email: [email protected]

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: [email protected]

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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 2 CFR Part 200.