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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
   
   
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

The purpose of this Notice of Funding Opportunity (NOFO) is to promote innovative preclinical, early phase clinical, and correlative studies that are hypothesis-driven and based upon established basic cancer research discoveries. By using the R21 mechanism, this NOFO will support exploratory/developmental projects in the advancement of novel anti-cancer agents, diagnostic tools, correlative biomarker identification, clinical approaches in treatment, symptom management, and prevention of common or rare tumors, as well as research on cancer disparities. These studies may involve considerable risk, but they would have the potential to lead to breakthroughs in particular areas, and/or to the development of novel techniques, agents, methodologies, models, or applications that could have a major impact on cancer research (preclinical or clinical).

This NOFO accepts only applications proposing research directly related to the development of novel approaches for cancer treatment, diagnosis, prevention, symptom management, or reduction of cancer disparities. Studies that focus on basic cancer biology, such as studies of cancer-related pathways or molecular mechanisms, are not responsive to this NOFO (see below for a more detailed description of studies that are not responsive to this NOFO).

Applicants are strongly advised to contact an appropriate NCI Scientific/Research Contact (see Section VII. Agency Contacts) prior to submission of their applications with questions regarding the responsiveness of their applications.

Applications for R21 awards should describe projects distinct from those supported through the traditional R01 mechanism. For example, such projects could assess, through preclinical or early phase clinical studies, the feasibility of a novel area of investigation or a new experimental system that has the potential to enhance patient-oriented research. Another example could include the unique and innovative use of an existing methodology to explore a new scientific area. Conversely, long-term projects, or projects designed to increase knowledge incrementally in a well-established area, will not be considered for R21 awards.

Applications submitted under this mechanism should break new ground or extend previous discoveries toward new directions or applications in the areas discussed below. Projects of limited cost or scope that use widely accepted approaches and methods within well-established fields are better suited for the R03 small grant mechanism, which is presently supported by the NCI Omnibus R03 FOA, PAR-20-052.

Specific Research Objectives

All areas of cancer research relevant to the mission of the Division of Cancer Treatment and Diagnosis (DCTD), the Division of Cancer Prevention (DCP), and the Center to Reduce Cancer Health Disparities (CRCHD), such as preclinical and clinical studies that focus on the development and testing of anti-cancer, symptom management, and cancer prevention interventions (drugs, biologics, natural products, dietary compounds or constituents, or complementary/alternative medicine), including combinations of agents; diagnostic and treatment methodologies; validation of predictive biomarkers for clinical use; and clinical and translational studies that seek to reduce the unequal burden of cancer in our society via research from underserved populations are appropriate for projects submitted to this NOFO. Testing (in prevention, symptom management, and/or treatment studies) of new models that closely parallel the development and progression of human cancers or the development of disease and treatment-related morbidities are also appropriate for this NOFO. In addition, comparative oncology studies of prevention, symptom management, and/or treatment of pet dogs with spontaneous cancers that serve as excellent models for human malignancies are acceptable for this NOFO.

Examples of the types of studies appropriate for this NOFO include, but are not limited to:

Clinical Studies:

• Exploratory, Phase I, or small Phase II trials of new agents, repurposed agents, or combinations of interventions (including radiation) for treatment of common or rare cancers, based on established mechanisms of action, demonstrable pre-clinical activity in relevant animal models, and pharmacological and toxicological data;
• Window-of-opportunity clinical trials to assess the effects of therapeutic doses of interventions on the patients tumors and their systemic effects, as well as associated correlative studies;
• Pilot trials of anti-cancer combination therapies to explore less toxic and more efficacious routes of administration, doses, dosing schedules, and sequences of individual interventions;
• Exploratory, Phase I, or small Phase II trials of new preventive agents or approaches (including medical devices, cancer preventive surgery, risk-reducing surgery, and non-surgical ablative techniques) to block, reverse, or delay of precancer or cancer, based on rational target selection and pharmacological and toxicological data;
• Exploratory, Phase I, or small Phase II trials of new agents, repurposed agents, or combinations of interventions (including radiation) for the prevention or treatment of acute and chronic symptoms and morbidities related to cancer and its treatment, based on established mechanisms of action, and pharmacological and toxicological data;
• Treatment of additional eligible cancer patients with age, racial/ethnic or health disparities during ongoing or prospective clinical trials to evaluate their differential responses (efficacy and toxicity) and resistance to the investigational regimens;
• Clinical studies for preliminary evaluation of the safety and efficacy of new cancer screening or imaging tools and techniques (devices, instrumentation, methods, and agents) designed to improve upon current technologies, practices, and interventions;
• Pilot trials of new radiation treatment modalities, and development of novel tools and approaches for radiation dosimetry and treatment planning/toxicity modulation.

Correlative Studies/Biomarker Development:

• Development and/or validation of novel assays to support the characterization and efficacy of cancer therapies or cancer prevention interventions;
• Early validation of biomarkers, such as (but not limited to) the following:
  • Predictive biomarkers that may lead to better cancer diagnosis and patient stratification, including imaging biomarkers or genetic/epigenetic signatures, using direct patient measurements or patient specimens from drug, biologic, radiation, or combination trials where the outcome is known;
  • Biomarkers elucidating molecular targets of interventions aimed at preventing or treating symptoms and/or toxicities resulting from disease or its treatment;
  • Biomarkers that may be used to predict or determine individual susceptibilities to symptoms and/or toxicities;
  • Biomarkers elucidating molecular targets of cancer preventive interventions;
  • Intermediate endpoint biomarkers for cancer prevention clinical trials;
  • Biomarkers or genetic signatures that may be used to detect or predict early recurrence;
  • Integration of biomarker measurements with imaging studies for the detection of early-stage cancers or to distinguish indolent from aggressive cancers;
  • Biomarkers or genetic/epigenetic signatures that may improve cancer diagnosis, patient stratification, and/or prediction of treatment response among diverse age, racial/ethnic, and/or underserved groups to better elucidate and decrease cancer disparities.
• Studies of particles, microvesicles, nucleic acids from tumor cells, and/or circulating tumor cells, for the purpose of cancer diagnosis, prognosis, detection of metastases, and cancer recurrence;
• Studies that correlate pathology image data with cancer diagnosis and prognosis;
• Studies that use high dimensional data (e.g., proteomic, genomic, or radiomic information) for cancer early detection, diagnosis, and disease stratification;
• Pharmacogenomic studies aimed at the identification of genomic profiles associated with increased/decreased efficacy or toxicity during clinical interventions;
• Correlation of the activation of specific signaling pathways with outcomes in immunotherapy clinical trials;
• Studies that use AI/machine learning models for the purpose of investigating cancer prevention, screening, or cancer symptom/toxicity modulation;
• Proton/image-guided radiation therapy dosimetry analysis of patient data;
• Dose-effect analysis of image-guided intervention (IGI) methods.

Target and Agent Development:

• Development of new molecular targeting agents or biologics for cancer treatment based on specific signaling pathways activated, or specific proteins expressed or amplified, during the process of tumorigenesis or tumor progression (including invasion and metastasis);
• Development of molecular targeting agents or biologics to reduce cancer therapy-related toxicity;
• Development of agents, biologics, or immunoprevention for cancer prevention or the treatment of pre-neoplasia;
• Development of molecular targeting agents, biologics, or novel strategies to enhance the effectiveness of immune therapies, including those that modulate the immunosuppressive tumor microenvironment;
• Evaluation of new combination treatment strategies and development of new agents to enhance the effectiveness of chemotherapy and other standard-of-care therapies;
• Development and preclinical evaluation of novel molecular agents and strategies to overcome therapeutic resistance;
• Performance of high-throughput screens for discovery of chemical probes and molecular targeting agents for cancer treatment;
• Development of theranostic agents.

Model Development and Analysis:

• Development and early validation of clinically relevant in vivo or in vitro (including 3D/organoid) models of common or rare tumors, when the purpose is to investigate diagnosis, treatment, and prevention strategies for human cancer (including efficacy of targeted therapies and treatment-related toxicity);
• Development and early validation of in vivo or in vitro models for the assessment, prevention, or treatment of cancer treatment-related toxicities;
• Development and early validation of in vivo or in vitro models for the assessment of immunoprevention or immunotherapy efficacy;
• Analysis of biological differences by race, age, and/or gender for the development of symptoms and/or toxicities;
• Analysis of clinical and genetic factors that may increase the incidence of symptoms and/or toxicities;
• Novel imaging approaches to characterize disease anatomy, physiology (including metabolism), and molecular biology (of the tumor and/or the microenvironment/vasculature) in order to guide the administration of targeted therapies in a clinical trial;
• Development of data acquisition methods and/or computational, mathematical, and animal models that can be used to assess imaging systems, including systems for IGI, and to improve image processing;
• Development of in vivo and in vitro models for the purpose of investigating cancer risk, when the purpose is to develop prevention strategies for human cancer;
• Development of in vivo and in vitro models for the purpose of investigating therapeutic outcome disparities among diverse racial/ethnic populations, including genetically engineered mouse models, patient-derived xenograft models, organoids, and cell lines;
• Comparative oncology studies to investigate diagnosis and treatment strategies for human disease. Co-clinical trials in dogs and humans are appropriate.

Applications Not Responsive to this NOFO

The following types of studies are not responsive to this NOFO. Applications proposing such studies will be considered non-responsive and will not be reviewed.

• Studies of basic science aspects of cancer biology, such as (but not limited to) studies of the following:
  • Basic cellular pathways, mechanisms, and oncogenic events that drive the development of tumors and behavior of cancer cells. Studies using therapeutic or preventive agents as tools/probes to interrogate basic cancer-related pathways and cellular mechanisms are not responsive to this FOA (although studies using agents for the purpose of studying therapeutic/preventive activity, mechanisms of drug action, or mechanisms of drug resistance are appropriate and responsive);
  • The role of tumor-initiating and cancer stem cells in tumorigenesis;
  • Epigenetic or transcriptional differences in tumor cells compared to normal cells;
  • Metabolic alterations in tumors and/or the tumor microenvironment (TME);
  • Features of the tumor microenvironment (TME) that contribute to cancer cell growth and survival;
  • Mechanisms of tumor progression, invasion, and metastasis;
• Development of in vivo or in vitro models of tumors, when the purpose is to interrogate basic oncogenic pathways or mechanisms;
• Phase III clinical trials (although studies using specimens from these trials are appropriate);
• Early-stage biomarker identification and validation using cell lines and in vitro model systems (although in vitro studies on methods of biomarker measurement -- for example, studies involving validated microphysiological systems or tissue chips -- are acceptable provided they are matched with human patient samples where outcomes are known or prospectively obtained);
• Risk assessment studies;
• Studies of behavioral interventions (although studies using specimens from these trials are appropriate);
• Studies that support epidemiological, behavioral, social, applied, and surveillance cancer research.

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

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Section II. Award Information

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)

Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are 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 and Notice of NIH's Interest in Diversity, NOT-OD-20-031.

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.

R&R or Modular 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:

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.

In addition, please include the following:

If the study is an ancillary project to a Parent Clinical Trial, the study record should relate to the ancillary project and not the Parent Clinical Trial.

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan

• Recruitment and referral sources: include the number of potentially available participants per proposed site annually;
• Enrollment rate (e.g., number of participants meeting eligibility criteria for enrollment per month);
• Discussion of potential recruitment delays or challenges and alternative strategies that can be implemented if there are enrollment delays or shortfalls;
• Procedures to monitor enrollment and track/retain participants for follow-up assessments;
• Evidence to support the feasibility of enrollment, including prior experience and yield from research efforts using similar referral sources and/or strategies;
• Strategies to ensure the study population has scientifically appropriate diversity and representativeness;
• Decision points for terminating the trial.

2.7 Study Timeline

The study timeline should describe key milestones throughout the project and trial that need to be met to achieve the goals of the study. A milestone is defined as a scheduled event in the project timeline that signifies the completion of a project stage or activity. Applicants are required to provide detailed project performance and timeline objectives as outlined below. Investigators must indicate where within the Plan the clinical trial or trials are scheduled and when the required documents will be available if not included at the time of submission. Program staff will review the milestones and timelines which can be negotiated, as needed, at the time of the award.

This section should include an estimated timeline for the following general milestones, as applicable:

• Completion of the finalized Clinical Trial Protocol for submission to NCI;
• Registration of clinical trial in ClinicalTrials.gov;
• Completion of regulatory approvals;
• Enrollment of the first subject;
• Enrollment of 25%, 50%, 75%, and 100% of the projected recruitment for all study participants including women, minorities, and individuals across the lifespan (as appropriate);
• Completion of data collection time period;
• Completion of primary endpoint and secondary endpoint data analyses;
• Completion of final report of the primary outcome;
• Reporting of results in ClinicalTrials.gov;
• Status of the FDA-regulated product requiring IND or IDE if applicable.

In addition to meeting the above recruitment and other targets, applicants should give contingency plans if they do not meet the milestones and address other implementation activities necessary such as start-up tasks to achieve trial completion. Future year support is contingent on satisfactory achievement of performance milestones. If milestones are not achieved fully, NCI may request development of a remedial plan and more frequent monitoring of progress, and/or take other remedial actions.

Section 3 - Protection and Monitoring Plans

3.3 Data and Safety Monitoring Plan

In addition to the description of safety monitoring, address plans to monitor trial performance, including plans to assure fidelity to the protocol and integrity of the data. Information about Data and Safety Monitoring Plans are available at https://humansubjects.nih.gov/data_safety.

3.5 Overall Structure of the Study Team

In addition to the standard requirements for this item, provide a description of methods to identify additional collaborators, including enrollment/participation sites, if applicable. Investigators who are new to the conduct of clinical trials should identify an appropriate mentor and establish the right composition for the clinical trial team (e.g., trial manager, statistician, data manager, study coordinator(s), research assistants, institutional review board [IRB] and ethics coordinator, etc.). In this situation, only the names and titles of key team members should be listed in a table.

Section 4 - Protocol Synopsis

4.1.a Detailed Description

It should summarize the necessary elements of the trial and supplement the Research Strategy, which includes an overview of the state-of-science and relevance of the trial and is meant to justify the need, its potential impact, and provide supporting preclinical and/or clinical evidence to justify the proposed trial, its design, and likelihood of successful completion. Applications submitted without the Clinical Protocol Synopsis are considered incomplete and will not be reviewed.

4.1.c Interventions

Please include the dose and intensity of the intervention in the description, if applicable.

4.3 Statistical Design and Power

The sample size and statistical power calculations should contain enough detail, including sufficient information on the assumptions made, so that a reviewer can readily duplicate the projected sample size for primary and secondary endpoints. The power analysis should include a discussion of non-compliance, potential cross-over (if applicable), account for rates of follow-up (i.e., drop out/lost to follow up) during key outcome collection contacts. A discussion of how missing data will be handled should be included. Planned interim analyses for safety, efficacy, and/or futility should be described, if applicable. For single-case design and other small-N study designs where traditional power analyses may not be applicable, provide a detailed description of the approach to sample size and analysis being used.

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.

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply- Application Guide.

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.

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 the NCI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

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.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

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. 

Not Applicable

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]

Applications Related to Cancer Treatment/Diagnosis (Preclinical Studies):

Morgan O'Hayre, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-7482
Email: [email protected]

Applications Related to Cancer Treatment/Diagnosis (Clinical Studies):

Anita Undale, MD, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5251
Email: [email protected]

Applications Related to Cancer Prevention/Symptom Management:

Marjorie Perloff, MD
National Cancer Institute (NCI)
Telephone: 240-276-7097
Email: [email protected]

Applications Related to Cancer Health Disparities:

Tiffany Wallace, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5114
Email: [email protected]

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

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
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.