Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)

Funding Opportunity Number (FON)
National Cancer Institute's Investigator-Initiated Early Phase Clinical Trials for Cancer Treatment and Diagnosis (R01 Clinical Trial Required)
Activity Code

R01 Research Project Grant

Announcement Type
Reissue of PAR-21-033
Related Notices

    See Notices of Special Interest associated with this funding opportunity

  • August 31, 2022- Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198.
  • August 5, 2022- Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189.
Funding Opportunity Number (FON)
PAR-24-085
Companion Funding Opportunity
PAR-24-072 , R01 Research Project
Number of Applications

See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)
93.393, 93.394, 93.395, 93.399
Funding Opportunity Purpose

Through this Notice of Funding Opportunity (NOFO), the National Cancer Institute (NCI) is soliciting research projects that implement early phase (Phase 0, I, and II) investigator-initiated clinical trials focused on cancer-targeted diagnostic and therapeutic interventions of direct relevance to the research mission of DCTD and OHAM. The proposed project must involve at least 1 clinical trial related to the scientific interests of one or more of the following research programs: Cancer Therapy Evaluation Program, Cancer Imaging Program, Cancer Diagnosis Program, Radiation Research Program, Complementary and Alternative Medicine Program and/or the HIV and AIDS Malignancies Research Programs. Applicants may propose to conduct an early phase trial by itself, or in combination with another research aim(s) as appropriate. This NOFO does not accept Phase III clinical trials.

Key Dates

Posted Date
December 15, 2023
Open Date (Earliest Submission Date)
January 05, 2024
Letter of Intent Due Date(s)

January 5, 2024

The following table includes NIH standard due dates marked with an asterisk.
Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed Scientific Merit Review Advisory Council Review Earliest Start Date
February 05, 2024 * March 05, 2024 * May 07, 2024 * July 2024 October 2024 December 2024
June 05, 2024 * July 05, 2024 * September 07, 2024 * November 2024 January 2025 April 2025
October 05, 2024 * November 05, 2024 * January 07, 2025 * March 2025 May 2025 July 2025
February 05, 2025 * March 05, 2025 * May 07, 2025 * July 2025 October 2025 December 2025
June 05, 2025 * July 05, 2025 * September 07, 2025 * November 2025 January 2026 April 2026
October 05, 2025 * November 05, 2025 * January 07, 2026 * March 2026 May 2026 July 2026
February 05, 2026 * March 05, 2026 * May 07, 2026 * July 2026 October 2026 December 2026
June 05, 2026 * July 05, 2026 * September 07, 2026 * November 2026 January 2027 April 2027
October 05, 2026 * November 05, 2026 * January 07, 2027 * March 2027 May 2027 July 2027

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.

Expiration Date
January 08, 2027
Due Dates for E.O. 12372

Not Applicable.

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

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

  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.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

Due to the introduction of the NIH policy, set forth in "NOT-OD-16-147," to create a Notice of Funding Opportunity (NOFO) that is specifically designed for applications that involve clinical trials, the National Cancer Institute (NCI) has established two program announcements for R01 applications to support investigator-initiated clinical trials that are now reissued as:

1. PAR-24-085 (this NOFO), which seeks applications for support of phase 0, I, and II medical imaging and oncologic interventional clinical trials relevant to the mission of the NCI's Division of Cancer Treatment and Diagnosis (DCTD); and Office of HIV and AIDS Malignancies (OHAM); and

2. PAR-24-072 (companion NOFO), which seeks applications for support of cancer prevention and control clinical trials relevant to the missions of NCI's Division of Cancer Prevention (DCP) and NCI's Division of Cancer Control and Population Sciences (DCCPS), respectively.

Applicants should be aware of the types of scientific programs that each named NCI Division manages to determine the appropriate NOFO defined above for submission of applications. In addition, NCI does not participate in the NIH-wide Research Project Grant (Parent R01 Clinical Trial Required) funding opportunity. However, applicants who want to request R01 support for clinical and translational cancer research projects that do not involve clinical trials can submit their application to the "NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)" NOFO.

Purpose

Through this Notice of Funding Opportunity (NOFO), the National Cancer Institute (NCI) intends to support research projects that include and implement early phase (Phase 0, I, and II) investigator-initiated clinical trials on cancer-targeted diagnostic and therapeutic interventions of direct relevance to the research mission of the NCI's DCTD and OHAM. All applications submitted to this NOFO should address the mission and priorities of one or more of the following programs:

1. the Cancer Therapy Evaluation Program (CTEP, DCTD);

2. the Cancer Imaging Program (CIP, DCTD);

3. the Cancer Diagnosis Program (CDP, DCTD);

4. the Radiation Research Program (RRP, DCTD);

5. the Office of Complementary and Alternative Medicine (OCCAM, DCTD); and

6. the Office of HIV and AIDS Malignancies (OHAM, Office of the Director).

Applicants can learn more about the various program goals, research priorities, and strategies developed to diagnose and treat cancer by visiting the DCTD website and the OHAM website.

Applications submitted to this NOFO must meet the NIH definition of a clinical trial (see NOT-OD-15-015) and provide specific clinical trial information as described in this NOFO and the NIH application FORMS-G guidelines (See: https://grants.nih.gov/grants/guide/notice-files/NOT-OD-21-169.html.).

Note: To help determine if your study meets the NIH definition of a clinical trial, review the case studies, the frequently asked questions, and answer the questions listed on the NIH Grants & Funding website at https://grants.nih.gov/ct-decision/index.htm. 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). Investigators who are new to the conduct of clinical trials are welcome to apply to this NOFO and participate in clinical trial research, but they are encouraged to identify appropriate mentors and to establish the right personnel compositions for the clinical trial teams.

Research Objectives

This NOFO is applicable to a broad range of clinical trial evaluations designed to improve the diagnosis and treatment of cancer in areas of common and unmet need. Each application should represent the applicant's or applicants' interest(s) and competencies, as well as the science related to diagnosis and treatment of cancer patients through well-designed and executed clinical trials. In addition, strategies to assess feasibility can include a novel area of investigation, new experimental systems, and/or existing technologies in a new area.

Although the rationale must be supported by preliminary data, the proposed clinical investigations may include study designs, methods, and interventions that are not themselves innovative but address important questions and/or unmet needs.

General Areas of Research

This NOFO is applicable to a broad range of clinical trial evaluations that improve the diagnosis and treatment of cancer in areas of common and unmet need. Potential areas of research may include, but are not limited to, the clinical evaluation of new or improved anticancer drugs and biologics, including immunotherapies, new or improved imaging technologies and surgical interventions, novel approaches to radiation therapy, and incorporation of complementary and alternative medicine approaches to treatment. The research component may include the development of therapeutics, diagnostics, and devices in combination with standard care therapies including chemotherapy, immunotherapy, surgery, radiotherapy, or any combination of these modalities. Additional research aims can be proposed as part of the overall research plan provided it includes at least 1 clinical trial to be completed within the project period.

Examples of projects appropriate to this NOFO include applications with the primary intent of conducting early phase clinical trial(s) for testing the efficacy, safety, clinical management, and/or implementation of novel therapeutic or diagnostic interventions, such as drugs, biologics, vaccines, stem cells, medicinal natural products, clinical laboratory tests, imaging agents, imaging devices, or image-guided therapies.

Applicants may, for example, propose to conduct an early phase clinical trial that:

  • Evaluates the dosing, safety, tolerability, pharmacokinetics, pharmacodynamics, and effectiveness of novel anticancer drugs, biologics, immunotherapeutics (e.g., adoptive cell transfer therapies), and their combinations as well as imaging agents or other interventions;
  • Tests approved agents and combinations for new indications;
  • Evaluates new or improved image-guided interventions, radiation modalities, means of delivery, or combinations with novel agents;
  • Tests imaging probes or quantitative approaches incorporated into commercially available imaging instrumentation (e.g., positron emission tomography [PET], single photon-emission computed tomography [SPECT], magnetic resonance [MR] imaging, computed tomography [CT], ultrasound [US], optical imaging, and photoacoustic imaging [PAI]);
  • Assesses tools, methods, devices, and instruments that can perform at the molecular, cellular, and organ levels;
  • Investigates multi-parametric imaging approaches and biomarker detection assays including radiomics, radiogenomics, genomics, proteomics, and metabolomics;
  • Evaluates imaging or laboratory biomarker activity, pharmacodynamic response, target engagement, dose-response trends;
  • Selects or ranks the best potential interventions, technologies, and/or dosing regimens to be evaluated in a subsequent trial, based on tolerability, safety data, biological activity, or preliminary clinical efficacy (e.g., a futility trial);
  • Conducts exploratory investigational new drug (IND) and/or investigational device exemption (IDE) studies (visit the FDA's website to obtain guidance documents on INDs, IDEs, and Clinical Trials; and
  • Evaluates integrative medicine approaches such as diets, nutrients, herbs, bioactive food components, pre/probiotics, microbiota practices, and mind-body interventions (e.g., acupuncture, exercise, meditation, and sleep) to improve standard of care or investigational therapeutics.

Research approaches should focus on interventions with outcome measures that contribute to the improvement of knowledge regarding mechanism of action or resistance, therapeutic index, prediction of response, standard-of-care practices, and/or quality of life. Research that combines expertise in more than one clinical research area (e.g., the development of therapeutics, diagnostics, and devices) is also welcome.

Prior to submitting applications to this NOFO, applicants are encouraged to review the NIH clinical trial case studies and frequently asked questions to determine if their clinical study meets the NIH definition of a clinical trial. Applicants should also consult with the Scientific/Research contacts for the area of science for which they are planning to develop an application. Early contact (at least 12 weeks prior to submission) is encouraged. This period provides an opportunity for the NCI staff to discuss the scope and goals, and to provide information and guidance to the applicants.

Type of Clinical trials to be supported by this NOFO

Clinical trials proposed must meet the NIH definition of a clinical trial (see NOT-OD-15-015) and should contribute to the advancement of evidence-based medicine/practice and the sciences that support it. Applicants may propose to conduct an early phase trial by itself, or in combination with other non-clinical trial research aims as appropriate. The NOFO will support the conduct of investigator-initiated oncologic intervention research at all early stages, from early mechanistic research and intervention development (e.g., stage 0 and/or I) through implementation and cost-effectiveness research. NCI funds may be used to support single-site, multi-site, hypothesis-driven, pathway-related, exploratory/feasibility and pragmatic trials (as defined below) designed to improve the management of care for patients with cancer. The trial design should be appropriate for the hypothesis to be tested. This NOFO also supports randomized phase II trials that can be performed within the temporal and fiscal limits of this program announcement. In addition, applicants may find the NIH-FDA Clinical Trial e-Protocol Writing Tool and Templates helpful in preparing phase II clinical trial protocols conducted under an FDA Investigational New Drug (IND) or Investigational Device Exemption (IDE) Application. These web-based resources, which is optional for use here, can be found at https://grants.nih.gov/policy/clinical-trials/protocol-template.htm.

Note that phase III clinical trials will not be accepted through this NOFO.

Description of the type of clinical trials that can be supported include:

  • Single site clinical trial(s): Early phase trials where the protocol is implemented by one investigational site that conducts and coordinates the protocol. While a single site clinical trial may enroll participants from multiple locations/clinics within a geographic area, those participants will receive an intervention or undergo outcome assessments under the direction and oversight of one research team at one investigational site.
  • Multi-site clinical trial(s): Early phase trials that recruit study subjects from two or more geographically distinct enrollment sites, or centers. The sites are usually distinct in other characteristics (e.g., demographic, socioeconomic, or clinical). Study protocols are followed at these sites.
  • Mechanistic clinical trial(s): Hypothesis-driven interventional studies (i.e., early phase trials) focused on basic and/or translational, discovery research on the biology and pathophysiology of cancer or the mechanism of action of an intervention.
  • Feasibility clinical trial(s): Early phase trials that propose to break new ground and/or extend previous discoveries toward new directions and/or applications.
  • Pragmatic trial(s): Early phase trials that test an intervention under the usual clinical conditions in which it will be applied, while explanatory trials do so under more idealized circumstances.
  • Ancillary clinical trial(s): Early phase trials that address research questions related to ongoing trials but are distinct from the primary/secondary objectives of the parent study. An ancillary clinical trial is an independent trial that includes an additional intervention prospectively assigned to patients or a subpopulation of patients within a larger trial. For helpful examples, see case studies 42b and 42c.
  • Pharmacodynamic trial(s): Early phase trials that link outcomes to measurements on pre- and post-treatment specimens to test hypotheses about therapeutic mechanisms based on pre-clinical data.
  • Biomarker-driven trial(s): Early phase trials that test predictive or prognostic biomarker findings obtained from pilot trials.
  • Co-clinical trial(s): Early phase trials that involve patients and in parallel (or sequentially) animal or human-in-animal models of cancer that mirror the genetics and biology of the patients malignancies or pre-cancerous lesions. The co-clinical trial should include either a therapeutic goal (e.g., the prediction, staging, and/or measurement of tumor response to therapies) or an early diagnostic goal.
  • HIV and AIDS related trials: Any of the above listed trial types conducted in individuals with an underlying human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).

Applications Not Responsive to this NOFO

Applications proposing these kinds of studies will not be considered responsive. Applications not responsive to this NOFO will not be reviewed.

  • Investigator-initiated phase III cancer-related medical/oncologic intervention and/or investigational imaging clinical trials as specified in the NCI policy for R01 and P01 activity codes found in Notice NOT-CA-13-012.
  • Applications involving only animal and/or in vitro studies that do not complement a trial are not appropriate; however, applications proposing both animal work and/or in vitro studies and a clinical trial are appropriate.
  • Applications proposing only observational studies that do not meet the NIH definition of a clinical trial. These studies may be submitted as R01s to the NIH Parent R01 Clinical Trial Not Allowed.
  • Clinical trials to investigate behavioral interventions without a therapeutic endpoint are not supported under this announcement but could be submitted to the NCI investigator-initiated clinical trials NOFO sponsored by DCP and DCCPS.
  • Planned or ongoing clinical trials performed by NCI-funded networks and special programs (e.g., National Clinical Trials Network (NCTN), Experimental Therapeutics Clinical Trials Network (ETCTN), and Specialized Programs of Research Excellence (SPOREs).
  • Clinical trial applications requesting to utilize the NCTN and/or ETCTN infrastructure and/or resources that do not have NCI prior approval. These programs operate under a cooperative agreement in which NCI has the responsibility for final review and approval of all protocols and subsequent amendments as well as the use of biospecimens collected in association with the Network trials. Applicants must consult the appropriate Principal Investigator of the NCTN Group or the ETCTN Lead Academic Organization to determine if NCI approval has been obtained for a potential submission.

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

Funding Instrument

Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed
New
Renewal
Resubmission
Revision

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Required: Only accepting applications that propose clinical trial(s).

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

Application budgets are limited to no more than $499,999 in direct costs per year.

Award Project Period

The maximum project period is 5 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

All organizations administering an eligible parent award may apply for a supplement under this NOFO.

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 (Organizations)
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.

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference 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 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.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) 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:

Lori A Henderson, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5930
Email: hendersonlori@mail.nih.gov

Page Limitations

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

Instructions for Application Submission

The following section supplements the instructions found in the How to Apply Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide must be followed.

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) 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 SF424 (R&R) Application Guide.

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

All instructions in the SF424 (R&R) 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 SF424 (R&R) Application Guide.

The following modifications apply:

For applications that have the complete Clinical Trial Protocol available, combine all clinical documents in a single PDF file in the Appendix. Resubmission applications that have modified the clinical trial(s) should indicate the changes in the Clinical Trial Protocol and update the Research Strategy section accordingly.

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 SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Note: If the proposed project consists of an ancillary clinical trial, please complete the study record with details of the ancillary study and not the parent trial/protocol.

Section 2 - Study Population Characteristics

Section 2.5 Recruitment and Retention Plan

Please include a discussion of the availability of potential participants for the proposed study and anticipated yield from recruitment and screening efforts. If there is more than one site, please provide a table showing the expected number and demographics of the population to be recruited at each site and overall. The plan should also include a discussion of experiences in recruiting and retaining similar populations, expected challenges to recruitment and retention, decision points for terminating the trial, and possible contingency plans.

Section 2.7 Study Timeline

The study timeline must 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 must include an estimated timeline for the following general milestones, as applicable:

  • Status of the FDA-regulated product requiring IND or IDE if 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;

Additionally, applicants should consider the following expectations when scheduling the above milestones:

NCI expects a protocol that meets the definition of a delayed start trial to have received full IRB approval with all regulatory requirements met (as appropriate) within the first year of the project period. Furthermore, NCI expects investigators proposing a delayed onset trial to have substantially engaged appropriate stakeholders and have all clinical trial planning activities completed within the first 3 years of the project. Applicants should also give contingency plans if they do not meet the milestones and address any other implementation activities necessary such as start-up tasks to achieve trial completion.

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 4 - Protocol Synopsis

Section 4.1 Study Design

4.1.a. Detailed Description

A detailed description of the protocol is required in this section regardless of the clinical trial protocol attachment in the Appendix. It should summarize the necessary elements of the trial and supplement the Research Strategy, which is meant to justify the need, its potential impact, and provide supporting preclinical and/or clinical evidence. Applications submitted without the Clinical Protocol Synopsis are considered incomplete and will not be reviewed.

Section 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. The power analysis should include a discussion of the anticipated level of adherence to the intervention and 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. Any planned interim analysis should also be described.

Section 5 - Other Clinical Trial-Related Attachments

Applicants should provide a list of clinical trials that demonstrate their experience in trial coordination over the last 5 years, without duplicating information in biosketches. A table should be provided as an attachment using the filename Clinical Trial Experience" just once. The table must 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.

Investigators who are new to the conduct of clinical trials must 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 the table.

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 SF424 (R&R) Application Guide must be followed.

For this NOFO, clinical trials designated as a delayed onset study are expected to be completed within the research project period .

PHS Assignment Request Form

All instructions in the SF424 (R&R) 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 SF424 (R&R) Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

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.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile 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 SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NCI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Any instructions provided here are in addition to the instructions in the policy:

  • Applicants that did not include the Clinical Trial Experience table in the Study Record: PHS Human Subjects and Clinical Trials Information - Section 5 - Other Clinical Trial-Related Attachments of their application will be asked to submit this document as part of the peer review post submission material following the policy guidelines described above.

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.

Overall Impact

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).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Specific for this NOFO: How appropriate and well-selected is the therapeutic or imaging strategy proposed for the Phase II trial in overcoming barriers to current methods of practice or the best available standard therapy?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance, and organizational structure appropriate for the project?

With regard to the proposed leadership for the project, do 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? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Specific to this NOFO: How likely will established investigators serving as the PI(s) succeed in the overall coordination of activities and reach trial completion based on information provided in their Clinical Trial Experience table (see table in the Study Record: PHS Human Subjects and Clinical Trials Information - Section 5 - Other Clinical Trial-Related Attachments") and/or their biosketches? For PI(s) who are new to, or less experienced with trial coordination/conduct, how significant is the mentor that was defined relative to the strength of the overall study team? How appropriate is the study team selected by the new investigator in meeting activities essential to the coordination and conduct of the trial?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Specific to this NOFO: If applicable, how likely can the Phase II clinical trial protocol be efficiently implemented and completed within the proposed time frame? Does the Phase II clinical trial protocol indicate an appropriate mechanism to capture, track, and monitor adverse events? Does the Phase II clinical trial protocol outline appropriate stopping rules or clear go/no decisions to mitigate risks? Are the plans to mitigate risks to participants and operations adequate?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment, and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there 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?

Additional Review Criteria

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.

Specific to this NOFO: Are the timelines and milestones listed in section 2.7 Study Timeline of PHS Human Subjects and Clinical Trials Information achievable within the time frame of the project?

Study Timeline


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)?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

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

Renewals

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.

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the Resource Sharing Plan(s) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review, in accordance with NIH peer review policies and practices, 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.

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

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.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

If a recipient is successful and receives a Notice of Award, 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.

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 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.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 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.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Data Management and Sharing

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.

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. 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.

The Federal Funding Accountability and Transparency Act of 2006 as amended (FFATA), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 2 CFR Part 200.113 and Appendix XII to 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 2 CFR Part 200 Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

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: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-637-3015

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

For Therapeutic Studies:
Lori A. Henderson, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5930
Email: hendersonlori@mail.nih.gov

For Imaging Studies:
Lalitha Shankar, MD, PhD
National Cancer Institute (NCI)
Telephone: 240-276-5936
Email: ls419z@nih.gov

For Radiation Research Studies:
Jeff Buchsbaum, M.D., Ph.D., AM
National Cancer Institute (NCI)
Telephone: 240-276-5914
Email: jeff.buchsbaum@nih.gov

For Biomarker Studies:
Tracy G. Lively, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5944
Email: livelyt@mail.nih.gov

For Complementary and Alternative Medicine Studies:
Dan Xi, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6143
E-mail: xida@mail.nih.gov

For HIV and AIDS Studies:
Rebecca Liddell Huppi, Ph.D.
National Cancer Institute
Telephone: 240-781-3324
Email: liddellr@exchange.nih.gov

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: crystal.wolfrey@nih.gov

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.

Authority and Regulations

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.

NIH Office of Extramural Research Logo
Department of Health and Human Services (HHS) - Home Page
Department of Health
and Human Services (HHS)
USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.