Part 1. Overview Information

Key Dates

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

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

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

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

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

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

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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

This notice of funding opportunity (NOFO) will support studies for the acquisition of data critical to completing the protocol of a full-scale multi-center Phase II or later phase trial. Applicants must describe the proposed future clinical trial and identify the specific issues for which additional data would be beneficial in planning a feasible future trial. Preliminary efficacy or effectiveness data to justify the future intervention trial must already exist at the time of application. Although the scientific literature or preliminary data may provide the rationale for conducting a future clinical trial, investigators often lack critical information about the study population, intervention, outcome, or operational risks necessary to finalize the trial protocol completely. The immediate goal is that the proposed planning activities will yield information that is both scientifically necessary and also sufficient to permit final decisions about the design or conduct of the clinical trial that increase rigor and feasibility. Preliminary studies may be needed to fill information gaps and address unknowns. This can include a pilot/ feasibility clinical trial if necessary, thereby improving future trial design and rigor.

Background

Unlike the R21 mechanism that is intended to obtain data that will support a future R01 grant, the U34 mechanism cannot be used for the collection of preliminary efficacy or effectiveness data to support the rationale for the subsequent clinical trial. Rather, the U34 mechanism may support planning activities to collect feasibility data, additional efficacy or effectiveness data, test accrual strategies, and address study design questions for a future trial. The information obtained using a U34 planning grant is intended to address issues that allow investigators to make decisions about whether the future trial should progress and, if so, what study design changes are necessary. Development of this U34 mechanism is meant to fill a gap in cancer prevention and control trials and facilitate study through our NCI-funded prevention and control clinical trials networks including but not limited to ULACNet, CP-CTNet, and NCORP.

Scope

The activities required will depend on the type of study (e.g., screening study, drug/device/biologics trial, behavior intervention, cancer care delivery). A pilot/ feasibility trial is allowed but is not required and should only be included if it is essential to the goals of the project.

Examples of research needs include but are not limited to the following:

• Perform studies to refine the appropriate study population, intervention, outcome, and/or study endpoint.
• Collect information necessary to identify appropriate recruitment methods and estimate available populations, screening-to-enrollment yield, attrition rate, or response rate with a focus on ensuring a diverse and adequate study population.
• Adapt and test an intervention or outcome instrument for a population that differs culturally from the population for which the instrument was originally designed and evaluated.
• Identify the appropriate control or comparison group to use in the subsequent clinical trial.
• Modeling data to support trial assumptions in the study design.
• Statistical planning and design
• Standardize the intervention or outcome across multiple sites.
• Test the feasibility of an outcome or intervention in the field.
• Determine the acceptability of the intervention to study participants.
• Determine whether adequate adherence to the intervention is achievable.
• Standardize and validate survey instruments.
• Develop methods for measuring intervention fidelity.
• Standardize and test the effectiveness of training tools.

Research Objectives

This NOFO is intended to support applications that address research questions that are within the mission of the Division of Cancer Prevention or Division of Cancer Control and Population Sciences.

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

• Cancer prevention and interception: testing of interventions (including nutritional compounds, drugs, small molecules, vaccine and biologics) and approaches (including medical devices, cancer preventive surgery, risk-reducing surgery, and non-surgical ablative techniques) to block, reverse, or delay the early stages of cancer (including treatment of preneoplastic lesions).
• Cancer screening: studies of clinical impact (harms as well as benefits) of cancer early detection technologies and practices, such as imaging and molecular biomarker approaches;
• Early detection: clinical utility of biological markers for early cancer detection and cancer risk assessment;
• Behavioral research in cancer prevention and control: testing of interventions addressing cancer risk behaviors such as: tobacco use, obesity prevention and management, sedentary lifestyles and poor diets; UV exposure; alcohol use. In addition, interventions of interest include those designed to improve vaccine uptake; immune function; sleep and circadian function; screening behavior; adherence to cancer prevention or treatment regimens; biopsychosocial processes of cancer-related behavior; communication and shared decision-making; environmental modifications and policy changes aimed at altering cancer-related health behaviors and/or preventing or improving cancer-related risks and outcomes;
• Susceptibility to cancer and cancer-related outcomes: strategies to translate clinical, environmental and genomic/genetic determinants of cancer occurrence and outcomes into evidence-based interventions for clinical and public health practice;
• Implementation science: strategies to promote the adoption, implementation, and sustainability of evidence-based intervention into routine healthcare and public health settings or the deimplementation of ineffective interventions;
• Healthcare delivery: single and multi-level interventions addressing the organization and/or delivery of cancer care (e.g., team-based care; novel use of electronic health records; new organizational mechanisms/staffing such as patient navigation; new models of specialized services such as palliative care or survivorship programs);
• Cancer survivorship: interventions addressing the physical, psychological, social, and financial burden of cancer and its treatment among survivors of cancer and their families (e.g., social functioning, caregiver adaptation);
• Supportive and palliative care: care/symptom science: intervention studies to prevent or treat acute and chronic symptoms and morbidities related to cancer and its treatment (e.g., cancer-related pain, chemotherapy induced peripheral neuropathy, cardiotoxicity, neurocognitive deficits, fatigue, sleep, etc.) as well as studies addressing the psychological impact of cancer and its treatment (e.g., stress, anxiety, depression); and/or
• Quality of Life (QOL): studies to improve the QOL (physical, functional, emotional, psychological, and social well-being) of patients.

Non-Responsive Applications

Applications with the following attributes will be deemed non-responsive and will not be reviewed:

• Applications that are first-in-human studies.
• Applications that only propose to write a protocol or manual, develop infrastructure, or implement an already fully designed trial.
• Applications that include purely mechanistic work or contain animal studies.
• Applications that lack a milestone plan or a future clinical trials description.
• Applications for an intervention without preliminary efficacy or effectiveness data.

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

Plan for Enhancing Diverse Perspectives (PEDP)

The NIH recognizes that teams comprised of investigators with diverse perspectives working together and capitalizing on innovative ideas and distinct viewpoints outperform homogeneous teams. There are many benefits that flow from a scientific workforce rich with diverse perspectives, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved populations participate in, and benefit from research, and enhancing public trust.

To support the best science, the NIH encourages inclusivity in research guided by the consideration of diverse perspectives. Broadly, diverse perspectives can include but are not limited to the educational background and scientific expertise of the people who perform the research; the populations who participate as human subjects in research studies; and the places where research is done.

This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP), which will be assessed as part of the scientific and technical peer review evaluation.  Assessment of applications containing a PEDP are based on the scientific and technical merit of the proposed project. Consistent with federal law, the race, ethnicity, or sex of a researcher, award participant, or trainee will not be considered during the application review process or when making funding decisions.  Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.

The PEDP will be submitted as Other Project Information as an attachment (see Section IV).  Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP Guidance materials.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

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

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

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

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

Applicant Organizations

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

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

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

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

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019 and Notice of NIH's Interest in Diversity, NOT-OD-20-031.

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

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:

Brandy Heckman-Stoddard, Ph.D., M.P.H.
Division of Cancer Prevention
National Cancer Institute (NCI)
Telephone: 240-276-7048
Email: [email protected]

Page Limitations

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

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

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Milestone Plan: The filename "Milestone Plan.pdf" should be used and the attachment should not exceed 2 pages.

The applicant is required to provide detailed information and timelines for completing all necessary planning activities. Milestones should be easily measurable and realistic. Milestones for meeting the requirements of the network through which the study will be conducted must be included. This plan should detail how the team will work with the research base or LAO to accomplish these milestones. Milestones may include, as applicable, but are not limited to:

• Development of a Manual of Operations
• Development of case report forms
• Database programming
• Development of the research team
• Identification of studysites
• Identification of a central laboratory and other relevant service cores
• Development of study organization and governing principles, if appropriate, including a Publications Policy and an Ancillary Studies Policy
• Development of training materials and policies for staff certification and site initiation
• Establishment of a single IRB and initiation of the IRB approval process
• Plans for obtaining study drug, other intervention materials, or placebo if appropriate
• Obtaining an Investigational New Drug Application or Investigational Device Exemption, if appropriate

These milestones will be negotiated at the time of the award, as appropriate.

The Milestone plan is a separate document from the Study Timeline.

Future Clinical Trial Description: The filename "Future Clinical Trial Description.pdf" should be used and the attachment may not exceed 3 pages.

Provide a description to the extent known of the future clinical trial to provide context for information sought in the U34 award. The summary should not describe the pilot/feasibility trial that may be conducted during the U34 period of award.

Plan for Enhancing Diverse Perspectives (PEDP)

• In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of actionable strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity. 
• Applicants should align their proposed strategies for PEDP with the research strategy section, providing a holistic and integrated view of how enhancing diverse perspectives and inclusivity are buoyed throughout the application.
• The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured.
• The PEDP may be no more than 2 pages in length and should include:
  • Actionable strategies using defined approaches for the inclusion of diverse perspectives in the project;
  • Description of how the PEDP will advance the scientific and technical merit of the proposed project;
  • Anticipated timeline of proposed PEDP activities;
  • Evaluation methods for assessing the progress and success of PEDP activities.

Examples of items that advance inclusivity in research and may be appropriate for a PEDP can include, but are not limited to:

• Partnerships with different types of institutions and organizations (e.g., research-intensive; undergraduate-focused; HBCUs; emerging research institutions; community-based organizations).
• Project frameworks that enable communities and researchers to work collaboratively as equal partners in all phases of the research process.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as human subjects in clinical trials, including those from underrepresented backgrounds.
• Description of planned partnerships that may enhance geographic and regional diversity.
• Outreach and recruiting activities intended to diversify the pool of applicants for research training programs, such as outreach to prospective applicants from groups underrepresented in the biomedical sciences, for example, individuals from underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.
• Plans to utilize the project infrastructure (i.e., research and structure) to enhance the research environment and support career-advancing opportunities for junior, early- and mid-career researchers.
• Transdisciplinary research projects and collaborations among researchers from fields beyond the biological sciences, such as physics, engineering, mathematics, computational biology, computer and data sciences, as well as bioethics.

Examples of items that are not appropriate in a PEDP include, but are not limited to:

• Selection or hiring of personnel for a research team based on their race, ethnicity, or sex.
• A training or mentorship program limited to certain researchers based on their race, ethnicity, or sex.

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see PEDP Guidance materials.

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.

PEDP implementation costs:

Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7): https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: The goals and expected outcome(s) of the planning activities should be concisely stated in the Specific Aims section. These should be explicitly linked to specific objectives of the future trial.

Research Strategy: This section must address both the planning activities and the future trial.

The Research Strategy must include:

• A discussion of the significance of the problem being studied, the need for the future trial, and the potential impact of the results of the future trial;
• Sufficient details of the future clinical trial (e.g. study design, primary objective, inclusion and exclusion criteria, proposed study population, proposed study agent(s), preliminary sample size, primary and major secondary endpoints, duration of recruitment and follow-up, etc.) to allow assessment of the likelihood that a feasible clinical trial will be developed;The statistical methods, including the assumptions made for preliminary power calculations for the future study, must be described. The sample size and statistical power calculations must contain adequate detail for duplicating the analysis readily. 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;
• Details of any pilot/ feasibility clinical trial that will be conducted as part of the award and the metrics that would signify success;
• A description of the potential problems, alternative strategies, and benchmarks for the success of the planning activities and future trial;
• A description of the planning activities to be carried out including stakeholder engagement;
• A discussion of how the proposed activities address any major barriers to the timely and successful implementation of the future trial;
• Information about how the future trial documents, and planning trial documents (if applicable), will be developed;
• A description of how the trial will be organized and managed, including the plans to identify and select additional collaborators, if applicable; and
• A concise description of the milestone plan.

Letters of Support: Provide all appropriate letters of support for the planning activities, including any letters necessary to demonstrate the support of consortium/site participants including the research base or Lead academic organization (LAO) that will support the future study, cores, laboratories, pharmacies, and other collaborators, including cost-sharing by NIH resources, in the case of intramural collaborators. If co-funding or in-kind support is planned from any source (non-NIH sources or NIH sources), letter(s) outlining details of the commitment (e.g. type, amount, and source of support), signed by a business official on organization letterhead, must be included. Letters of support should also be provided from individuals or organizations that have been or will be involved in stakeholder engagement efforts.

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.

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Other Plan(s): 

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

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

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

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

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan (for the planning study)

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

2.7 Study Timeline

The study timeline should describe key milestones throughout the planning study, not the future trial, that needs 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. Program staff will review the milestones and timelines which can be negotiated, as needed, at the time of the award.

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

• Registration of clinical trial in ClinicalTrials.gov;
• Completion of regulatory approvals;
• Enrollment of the first subject;
• Enrollment of 10%, 25%, 50%, 75%, and 100% of the projected recruitment for all study participants including women, minorities, and children (as appropriate);
• Completion of data collection time period;
• Completion of primary endpoint and secondary endpoint data analyses;
• Completion of the final report of the primary outcome;
• Reporting of results in ClinicalTrials.gov;
• Status of the FDA-regulated product requiring IND or IDE if applicable.

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

Section 4 - Protocol Synopsis

4.1.a Detailed Description

It should summarize the necessary elements of the planning study, not the future trial, and supplement the Research Strategy, which includes an overview of the state-of-science and relevance of the trial.

4.1.c Interventions

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

4.3 Statistical Design and Power

The sample size and statistical power calculations should contain enough detail about the planning study, not the future trial, including sufficient information on the assumptions made so that a reviewer can readily duplicate the projected sample size for primary and secondary endpoints related to feasibility. The power analysis should include a discussion of non-compliance, potential cross-over (if applicable), account for rates of follow-up (i.e., drop out/lost to follow up) during key outcome collection contacts. A discussion of how missing data will be handled should be included.

Delayed Onset Study

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

PHS Assignment Request Form

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

Foreign Organizations

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

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

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.

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

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

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected].

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

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

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

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

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NCI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

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

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions, consistent with applicable law.

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

Please note that reviewers will not consider race, ethnicity, age, or gender of a researcher, award participant, or trainee, even in part, in providing critiques, scores, or funding recommendations. NIH will not consider such factors in making its funding decisions.

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. 

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

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

• Development of research strategy for the planning of the future clinical trial and appropriate conduct, monitoring, and results reporting of the pilot/ feasibility trial if conducted.
• Collaborating with the network research base or LAO to provide statistical expertise for effective scientific design, conduct, and data management of future clinical trials and other human subjects research conducted through the award.
• Any involvement of a third-party (including but not limited to industry, academia, and non-profit institutions) in the study and network activities that includes access to any network generated resources (i.e., data and biosamples, or study results that are not publicly available, or using the name of the network or study or the name of the NIH or NCI, is permitted only after written permission by the NCI Program staff who will consult with others at NIH and NCI Technology Advancement Office.
• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
• Recipientsmust comply with the guideline and standard operating procedures of the network through which future trials will be conducted.

In addition:

• PDs/PIs may be expected to supply additional progress-related information, in addition to the standard annual Research Performance Progress Report (RPPR) submission based on the network through which the study will be conducted.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

An NCI Program staff member(s) acting as a Project Scientist(s) will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. Additional NCI staff members may be designated to have substantial involvement (as Project Scientists).

The main responsibilities of substantially involved NCI staff members include, but are not limited to, the following activities:

• Ensuring that the clinical trial proposed is within the research scope of the network.
• Ensuring the concept receives all the required approvals through the network.
• Serving as a resource for scientific information on trial/study design.
• Working with recipients to collaboratively manage issues associated with their participation in the conduct of clinical trials across the network.
• Informing the PDs/PIs of scientific opportunities resulting from NCI-supported clinical research programs and facilitating collaborations between the recipient, the network, and other NCI-sponsored programs.
• Facilitating formal aspects of collaborations with outside organizations including review of any memoranda of understanding and data/material transfer agreements for compliance with NIH/NCI and federal policies.
• Negotiating and evaluating compliance with the milestone plan.
• Review compliance with applicable HHS, FDA, OHRP, NIH, and NCI regulations for clinical research involving human research subjects.
• Monitoring the progress and performance of the key components of the award.

Additionally, an NCI program director acting as Program Official (PO) will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The PO will ensure that there is no budgetary overlap between the network funding and the U34 funding.

The NCI will have access to all data (including imaging data) collected and/or generated under this Cooperative Agreement and may periodically review the data. The NCI may also review all records related to recipients performance under the award for appropriate collection, review, and distribution of biospecimens collected in association with network trials.

The NCI reserves the right to reduce the budget or withhold an award in the event of substantial recipient underperformance (e.g., vastly insufficient participant accrual per the protocol specified) or other substantial failures to comply with the terms of the award.

Areas of Joint Responsibility

• General aspects of collaboration on study development and conduct especially with respect to compliance with federal regulations for clinical trial research.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

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

4. Reporting

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

• Recipients will provide updates at least annually on implementation of the PEDP.

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

Section VII. Agency Contacts

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

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

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

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

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

For cancer prevention, early detection, screening, and symptom management-related clinical trials, contact:
Brandy Heckman-Stoddard, Ph.D., M.P.H.
National Cancer Institute (NCI)
Telephone: 240-276-7048
Email: [email protected]

For cancer care delivery, contact:
Kate Castro, M.S., R.N.
National Cancer Institute (NCI)
Telephone: 240-276-5871
Email: [email protected]
 

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

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: [email protected]

Section VIII. Other Information

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.