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 and Background

Through this notice of funding opportunity (NOFO), the National Cancer Institute (NCI) invites applications for support of investigator-initiated clinical trials related to the programmatic interests of the NCI Division of Cancer Prevention and/or the NCI Division of Cancer Control and Population Sciences that have the potential to reduce the burden of cancer through improvements in early detection, screening, prevention and interception, healthcare delivery, quality of life, and/or survivorship related to cancer; with such attributes, the proposed studies should also have the potential to improve clinical practice and/or public health. Applications submitted to this NOFO must include studies that meet the National Institutes of Health (NIH) definition of a clinical trial (see NOT-OD-15-015 for details) and provide specific clinical trial information as described in this NOFO and the application instructions. This NOFO does not and will not support clinical trials for studies of cancer diagnosis and/or oncologic therapy in patients.

Due to the introduction of a National Institutes of Health (NIH) policy, set forth in NOT-OD-16-147, to create notices of funding opportunity announcements (NOFOs) that are specifically designed for applications that involve clinical trials, the National Cancer Institute (NCI) has established two R01 investigator-initiated clinical trials required program announcements. This NOFO is to support Phase 0-IV clinical trials with the potential to reduce the burden of cancer for patients and other affected persons through improvements in early detection, prevention, healthcare delivery, quality of life, and/or survivorship related to cancer, all of which are program areas identified by NCI's Division of Cancer Prevention (DCP; https://dcp.cancer.gov) and/or NCI's Division of Cancer Control and Population Sciences (DCCPS; https://dccps.cancer.gov). This NOFO does not and will not support clinical trials to study cancer diagnoses and/or medical interventions (oncologic treatments) in cancer patients; such research will be supported through another NOFO, PAR-25-081, which is relevant to phase 0, I, and II interventional clinical trials supported by NCI through its Division of Cancer Treatment and Diagnosis (DCTD).

An application to be supported by this NOFO must propose a Phase 0-IV clinical trial involving investigations in cancer prevention or control that should contribute to the advancement of evidence–based medicine and the practice that supports it. NIH defines a clinical trial as "a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes" (NOT-OD-15-015). Applications submitted to this NOFO must meet the NIH definition of a clinical trial and provide specific clinical trial information as described in this NOFO and the NIH application FORM H guidelines (NOT-OD-22-195). Furthermore, investigators who are involved in clinical trials supported through this NOFO are  expected to follow the NIH Policy on Good Clinical Practice (see NOT-OD-16-148).

General Area of Research

This NOFO is applicable to a broad range of research supported through the NCI's Division of Cancer Prevention (DCP) and the NCI's Division of Cancer Control and Population Sciences (DCCPS).

Examples of relevant areas of research include but are not limited to:

• Cancer prevention and interception: development and testing of interventions (including diet, nutritional compounds, drugs, small molecules, vaccine and biologics) and approaches (including physical activity, medical devices, cancer preventive surgery, risk-reducing surgery, and non-surgical ablative techniques) to block, reverse, or delay the early stages of cancer (including treatment of preneoplastic lesions and presurgical trials in early stage cancer with the intent of developing an agent/intervention for cancer prevention). This also includes studies examining mechanism and surrogate biomarkers of efficacy;
• Cancer screening: studies of operating characteristics and clinical impact (harms as well as benefits) of cancer early detection technologies and practices, such as imaging and molecular biomarker approaches;
• Early detection: studies for identification, development, and validation of biological markers for early cancer detection and cancer risk assessment;
• Behavioral research in cancer prevention and control: development and testing of interventions addressing risk behaviors such as: tobacco use, energy balance, alcohol use, or sun exposure; vaccine uptake; immune function; screening behavior; treatment adherence; biopsychosocial processes of cancer-related behavior; communication, decision science, environmental modifications and policy changes aimed at altering cancer-related health behaviors and/or preventing or improving cancer-related risks and outcomes;
• Susceptibility to cancer and cancer-related outcomes: strategies to translate clinical, environmental and genomic/genetic determinants of cancer occurrence and outcomes into evidence-based interventions for clinical and public health practice;
• Implementation science: strategies to promote the adoption, implementation, and sustainability of evidence-based intervention into routine healthcare and public health settings or the deimplementation of ineffective interventions;
• Healthcare delivery: single and multi-level interventions addressing the organization and/or delivery of cancer care (e.g., team-based care; novel use of electronic health records; new organizational mechanisms/staffing such as patient navigation; new models of specialized services such as palliative care or survivorship programs);
• Cancer survivorship: interventions addressing the physical, psychological, social, and financial burden of cancer and its treatment among survivors of cancer and their families (e.g., mental health, social functioning, caregiver well-being and adaptation);
• Supportive and palliative care: development and testing of interventions (including diet, nutritional compounds, drugs, small molecules, vaccine and biologics) and approaches for the prevention or treatment of acute and chronic symptoms and morbidities related to cancer and its treatment including those experienced by patients with metastatic cancer; and/or
• Quality of Life (QOL): studies to improve the QOL of patients.

Scope of Work and Additional Guidance

Applicants proposing to conduct behavioral intervention research are encouraged to use an existing framework, such as the ORBIT model for developing behavioral treatments (http://dx.doi.org/10.1037/hea0000161), to determine the clinical trial phase being proposed and for guidance on study designs and methods appropriate for early-phase (Phase 0, I, and II) translational behavioral research. Applicants may also wish to reference other frameworks in their application, such as the experimental medicine approach (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4656226/) as defined by the Science of Behavior Change Common Fund initiative when proposing basic, mechanistic, and early-phase translational behavioral studies (see doi: 10.1037/hea0001095. PMID: 34990185 for examples of behavioral translational frameworks). Applicants may propose to conduct a clinical trial or trials, or in combination with other research aims as appropriate.

This NOFO is not intended for observational studies, which may be submitted as R01 applications to the NIH "Parent" R01 NOFO, PA-20-185 or its future reissuance, or other relevant NIH NOFOs. Other types of human subject research that do not fit the NIH definition of a clinical trial may also be submitted to the NIH Parent R01 NOFO.

With regard to support for Phase III clinical trials, this NOFO will only support applications proposing Phase III clinical trials that are limited to public health interventions, healthcare delivery research (e.g., supportive care, palliative care, and symptom management), and other psychosocial, behavioral, environmental, policy, health system, or implementation strategies, and related interventions to address cancer prevention and control, provided they can be completed entirely within the grant cycle. This NOFO is not intended to support Phase III clinical trials to test the efficacy of cancer-related medical (oncologic) interventions or Phase III clinical trials of cancer imaging (or other diagnostic) modalities. Large trials may be subject to negotiated milestone plans.

Applications that propose clinical trials sought by and to be supported through this NOFO can include studies planned to be conducted through special NCI programs and networks such as, the Specialized Programs of Research Excellence (SPOREs), Cancer Centers, and/or the NCI Community Oncology Research Program (NCORP). The studies may include correlative laboratory, imaging studies, and/or other trial-related study endpoints. Investigators conducting studies in the NCORP should contact the NCI NCORP Research Base Program Officer prior to submission of the application. Budget requests for projects to be conducted through otherwise supported NCI clinical trials infrastructure cannot include support (i.e., funds) that would duplicate that already supported infrastructure.

Non-responsive Applications  

The following types of clinical trials are not responsive to this NOFO and applications proposing such activities will be deemed non-responsive and will not be reviewed:

• Phase III clinical trials to test the efficacy of cancer-related medical (oncologic) interventions;
• Phase III clinical trials of cancer imaging (or other diagnostic) modalities;
• Phase 0, I, and II medical imaging and oncologic interventional clinical trial covered by PAR-25-081.
• Clinical trial applications requesting to utilize the NCTN and/or NCORP infrastructure and/or resources that do not have NCI prior approval.

NOTE: Applicants to this NOFO are strongly encouraged to contact NCI staff as soon as possible in the development of the application (preferably no later than 12 weeks prior to the application due date) to discuss the details of their proposed clinical trial, so that NCI staff can help the applicant understand whether the proposed clinical trial is within the goals and mission of the NCI and is appropriate for this NOFO.

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

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 Government

• 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.

• 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 registration; 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.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Jessica M. Faupel-Badger, Ph.D., M.P.H.
Division of Cancer Prevention
National Cancer Institute (NCI)
Telephone: 240-276-7296
Email: [email protected]
 

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.

Other Attachments:

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-definedclinical 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.

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

Section 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:

• Complete 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

Section 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.

Section 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

Section 4.1.a Detailed Description

It should summarize the necessary elements of the trial and supplements 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.

4.1.d Study Phase

Applicants proposing behavioral intervention research are encouraged to use an existing framework, such as the ORBIT model for developing behavioral treatments (http://dx.doi.org/10.1037/hea0000161), to determine the clinical trial phase being proposed and for guidance on study designs and methods appropriate for early-phase (Phase I and II) translational behavioral research.

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.

Section 5 - Other Clinical Trials-Related Attachments

5.1 Other Clinical Trials-related Attachments

For applications that have the complete Clinical Trial Protocol available, submit the Clinical Trial Protocol as a single PDF that combines all clinical documents.  

Applicants should provide a list of clinical trials that demonstrate their experiences in trial coordination over the last 5 years, without duplicating information in biosketches. The table should be provided as an attachment using the filename “Clinical Trial Experience." The table should also include the following for each trial listed: start and completion date; percent of target accrued; whether the trials reached completion; and, if applicable, the date of first publication.

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.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions 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. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH 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 components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 8 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

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.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Review Criteria

Reviewers will consider 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 factor score. 

Factor 1: Importance of the Research

Significance

• Evaluate the importance of the proposed research in the context of current scientific challenges and opportunities, either for advancing knowledge within the field, or more broadly. Assess whether the application addresses an important gap in knowledge in the field, would solve a critical problem, or create a valuable conceptual or technical advance.
• Evaluate the rationale for undertaking the study, the rigor of the scientific background for the work (e.g. prior literature and/or preliminary data) and whether the scientific background justifies the proposed study.

Innovation

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

Specific to this NOFO:

• Evaluate the potential for the proposed research to improve scientific knowledge, technical capability, and/or clinical practice or to lead to changes in the concepts, methods, technologies, treatments, services, or preventative interventions currently used in the field.
• Evaluate whether the design/research plan includes innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice.

Factor 2. Rigor and Feasibility

Approach

• Evaluate the scientific quality of the proposed work. Evaluate the likelihood that compelling, reproducible findings will result (rigor) and assess whether the proposed studies can be done well and within the timeframes proposed (feasibility).

Rigor:

• Evaluate the potential to produce unbiased, reproducible, robust data.
• Evaluate the rigor of experimental design and whether appropriate controls are in place.
• Evaluate whether the sample size is sufficient and well-justified.
• Assess the quality of the plans for analysis, interpretation, and reporting of results.
• Evaluate whether the investigators presented adequate plans to address relevant biological variables, such as sex or age, in the design, analysis, and reporting.
• For applications involving human subjects or vertebrate animals, also evaluate:
  • the rigor of the intervention or study manipulation (if applicable to the study design).
  • whether outcome variables are justified.
  • whether the results will be generalizable or, in the case of a rare disease/special group, relevant to the particular subgroup.
  • whether the sample is appropriate and sufficiently diverse to address the proposed question(s).
• For applications involving human subjects, including clinical trials, assess the adequacy of inclusion plans as appropriate for the scientific goals of the research. Considerations of appropriateness may include disease/condition/behavior incidence, prevalence, or population burden, population representation, and/or current state of the science.

Feasibility:

• Evaluate whether the proposed approach is sound and achievable, including plans to address problems or new challenges that emerge in the work. For proposed studies in which feasibility may be less certain, evaluate whether the uncertainty is balanced by the potential for major advances.
• For applications involving human subjects, including clinical trials, evaluate the adequacy and feasibility of the plan to recruit and retain an appropriately diverse population of participants. Additionally, evaluate the likelihood of successfully achieving the proposed enrollment based on age, racial, ethnic, and sex or gender categories.
• For clinical trial applications, evaluate whether the study timeline and milestones are feasible.

Specific to this NOFO:

• Evaluate the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention is supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms.
• Evaluate whether the study design is justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested.
• Given the methods used to assign participants and deliver interventions, evaluate whether the study design is adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results. Evaluate whether the trial is appropriately designed to conduct the research efficiently including streamlining data collection to reduce site burden. Evaluate whether the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, are appropriate and well justified.
• Evaluate whether the process for obtaining informed consent or assent is appropriate. Evaluate whether the eligible population available.  Evaluate whether the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection. Evaluate whether there is the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria has been addressed.
• Evaluate whether the plan to obtain required study agent(s) is appropriate and whether the application proposes to use existing available resources, as applicable.
• Evaluate whether the planned analyses and statistical approaches are appropriate for the proposed study design and methods used to assign participants and deliver interventions.
• Evaluate whether the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable
• Evaluate whether methods for standardization of procedures for data management to assess the effect of the intervention and quality control have been addressed
• Evaluate whether there are adequate plans to complete data analysis within the proposed period of the award
• Evaluate whether the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines is appropriate
• Evaluate whether the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers and whether there are plans to add or drop enrollment centers, as needed.
• If international site(s) is/are proposed, evaluate whether the application adequately address the complexity of executing the clinical trial.
• If multi-sites/centers, evaluate whether there is evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure.

Factor 3. Expertise and Resources

Investigator(s)

• Evaluate whether the investigator(s) have demonstrated background, training, and expertise, as appropriate for their career stage, to conduct the proposed work. For Multiple Principal Investigator (MPI) applications, assess the quality of the leadership plan to facilitate coordination and collaboration.

Environment

• Evaluate whether the institutional resources are appropriate to ensure the successful execution of the proposed work.

Specific to this NOFO:

• Evaluate whether the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines.  Evaluate whether the PD/PI(s) and key personnel have appropriate expertise in study coordination, data management and statistics. For a multicenter trial, evaluate whether the organizational structure is appropriate and identifies a core of potential center investigators and staffing for a coordinating center.
• Evaluate whether the project will benefit from unique features of the scientific environment, subject populations, or collaborative arrangements.
• Evaluate whether the administrative, data coordinating, enrollment and laboratory/testing centers, are appropriate for the trial proposed.

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Study Timeline

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate? Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Vertebrate Animals

When the proposed research includes Vertebrate Animals, evaluate the involvement of live vertebrate animals according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards

When the proposed research includes Biohazards, evaluate whether specific materials or procedures that will be used are significantly hazardous to research personnel and/or the environment, and whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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.

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, evaluate the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Evaluate whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by CSR, 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. 

Successful recipients under this NOFO agree that:

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by any funded entity, recipients and subrecipient(s) are required to: Use health IT that meets standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if such standards and implementation specifications can support the activity.  Visit https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-D/part-170/subpart-B to learn more.

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by eligible clinicians in ambulatory settings, or hospitals, eligible under Sections 4101, 4102, and 4201 of the HITECH Act, use health IT certified under the ONC Health IT Certification Program if certified technology can support the activity. Visit https://www.healthit.gov/topic/certification-ehrs/certification-health-it to learn more.

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

        1) ongoing and consistent access to HHS owned or operated information or operational technology systems; and 

        2) receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

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]

For cancer prevention, early detection, screening, and symptom management-related clinical trials, contact:

Jessica Faupel-Badger, Ph.D., M.P.H.
National Cancer Institute (NCI)
Telephone: 240-276-7296
Email: [email protected]

For cancer control and population sciences-related clinical trials, contact:

Tanya Agurs-Collins, Ph.D., R.D.
National Cancer Institute (NCI)
Telephone: 240-276-6956
Email: [email protected]

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Crystal Wolfrey
National Cancer Institute
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.