Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

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

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

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

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

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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

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-25-081 (this NOFO), which seeks applications for support of early phase (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-25-167 (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 NOFO, the 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-H 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., Phase 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 applications may be submitted as R01s to the NIH Research Project Grant (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

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)

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

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Page Limitations

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

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

Other Plan(s): 

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

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 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.

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 How to Apply- 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 How to Apply- Application Guide must be followed.

Foreign Organizations

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

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

See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the How to Apply-Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

Applications must be submitted electronically following the instructions described in the How to Apply Application Guide. Paper applications will not be accepted.

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply Application Guide.

See more tips for avoiding common errors.

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

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov.

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.

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

Reviewers will evaluate Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate criterion score. 

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

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

2. Review and Selection Process

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

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

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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

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

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

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

2. Administrative and National Policy Requirements

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

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

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

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

Not Applicable

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

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

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (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: support@grants.gov

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:
Magdalena Thurin, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5973
Email: magdalena.thurin@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
 

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 (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.

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.