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.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

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

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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

The purpose of the National Cancer Institute (NCI)-supported Cancer Prevention Clinical Trials Network (CP-CTNet) is to perform early phase clinical trials to evaluate the biologic effects of preventive agents and interventions and to determine clinically-relevant correlates in order to advance their development for cancer prevention.

CP-CTNet will support the following two types of components that will be individually awarded through two Notice of Funding Opportunity (NOFO) announcements indicated below:

• CP-CTNet Site, whose role will be to design, perform and report the results of early phase (phase 0-II) cancer prevention clinical trials (this NOFO). 
• Data Management, Auditing, and Statistical Center (DMASC), which will provide centralized data management, statistical support, and auditing of clinical trials data, as well as administrative support for all CP-CTNet recipients (covered by companion NOFO, RFA-CA-24-025).

Each CP-CTNet Site will consist of a Lead Academic Organization (LAO) and Affiliated Organizations (AOs) that will work together to perform clinical trials.  Each CP-CTNet LAO will serve as the research hub for its group and will be the UG1 applicant institution. Each LAO will constitute a multi-institutional clinical trial group and provide the infrastructure to develop, implement, and analyze the studies. The Clinical trials will be performed either by the LAO and/or AOs within each CP-CTNet site or across the CP-CTNet sites (cross-network trials).

Key Definitions for the context of this NOFO:

• The terms “Clinical Research” and “Clinical Trials” in this NOFO follow the NIH definitions (https://grants.nih.gov/policy/clinical-trials/glossary-ct.htm#ClinicalResearch.)
• CP-CTNet Site: UG1 Consortium supported by RFA-CA-24-024 consisting of the Lead Academic Organization (LAO, recipient of the UG1 award) and Affiliated Organizations (AOs). Each LAO serves as the research hub for the CP-CTNet Site. A LAO may have parts that represent the same legal entity, even if their location is different from the main location of the awardee (such parts are referred to as "LAO integrated components"). AOs are any institutions collaborating with the LAO on clinical trials under sub-contractual/consortium arrangements.
• Study Chair: the investigator who leads a given clinical trial
• Target organ: organ of focus for a given clinical trial. The clinical trial will provide information about prevention or interception of cancer arising from the specific target organ. 
• NCI Central Institutional Review Board (CIRB): a centralized approach to human subject protection through a process that streamlines local IRB review of selected NCI-sponsored trials for institutions across the country by relying on national experts to ensure trials are reviewed efficiently and with the highest ethical and quality standards (https://www.ncicirb.org/about-cirb/).
• An Accrued Participant is defined as an individual who has completed the informed consent process, has been deemed eligible through all levels of the screening process, and has started the study intervention (e.g., actually received the agent and/or intervention to be tested).
• A Screened Participant is defined as an individual who has signed consent to proceed with evaluation for eligibility for a study after preliminary eligibility (e.g., presence of a risk factor for a specific cancer, history of a specific premalignant lesion, etc.) has been determined.
• Cross-network trial: a trial performed across two or more CP-CTNet Sites such that funding for the trial is provided from the grants to all of the participating CP-CTNet Sites

Note: It is essential that applicants for this NOFO are also fully familiar with the companion NOFO, RFA-CA-24-025, including the specific goals and other vital details of the DMASC's functions within the CP-CTNet.

Background

The search for effective cancer preventive agents, in the context of a rapidly advancing molecular understanding of the process of carcinogenesis, has led to the study of an increasing number of agents that intervene in specific molecular pathways thought to be critical to cancer development. The rapidly advancing, albeit incomplete, understanding of the early phases of cancer development provides a strong rationale for increased investment in cancer prevention. There has been a longstanding interest in infectious etiologies of cancer and highly effective preventive vaccines (human papillomavirus, hepatitis B) or treatments (hepatitis C) are now integrated into standard care. Targeting these obligatory causes of cancer has profound consequences on public health. For instance, in the case of human papillomavirus, an effective country-wide vaccination program in the UK led to a highly significant population-level decrease in cervical cancer, as high as 97% when vaccinations were given at age 12-13 years. More recently, the recognition of the importance of the role of the immune system in tumor development and the recent successes in cancer immunotherapy for the treatment of advanced malignancies have led to a resurgence of interest in immunopreventive approaches aimed at cancers not associated with infections. The increasing number and molecularly or immunologically targeted nature of new agents require an efficient clinical trials system for evaluation and screening prior to moving to larger definitive phase III trials. These complex trials must also include extensive biomarker analyses, investigation of the biologic effects of the agent on the intended target, and correlation with clinically relevant indicators of potential health outcomes.

The nature of cancer prevention clinical trials requires access to specialized high-risk populations who obtain their care from different subspecialists and expertise in tissue collection and biomarker analysis. A typical phase II trial might examine the effect of an intervention on a histologically-proven premalignancy in participants at risk for cancer. This requires the screening of multiple high-risk individuals with invasive procedures, such as a colonoscopy or bronchoscopy, to identify those who harbor such premalignancies, followed by post-treatment procedures with biopsies to assess the intervention’s efficacy. Other types of studies employed in cancer preventive agent development include (but are not limited to): phase 0 micro-dosing trials, phase I pharmacokinetic and pharmacodynamic trials, and window-of-opportunity trials performed prior to definitive cancer treatment. Individuals participating in such studies include healthy volunteers, individuals at high risk for cancer either due to genetic predisposition or the presence of premalignant lesions, and cancer patients either prior to or after definitive treatment of the primary malignancy. Thus, multi-institutional groups of clinicians from diverse specialties, research nurses, pathologists, translational scientists, statisticians, data managers, and other personnel with expertise in cancer prevention, drug development, and biomarker analysis are needed to successfully perform increasingly complex cancer prevention clinical trials.

NCI supports the systematic development of cancer preventive agents through three major programmatic initiatives managed by the Division of Cancer Prevention (DCP):

• Preclinical agent development is supported through the PREVENT Cancer Preclinical Drug Development Program and the Cancer Prevention-Interception Targeted Agent Discovery Program (CAP-IT). 
• The early phase clinical development (phase 0-II clinical trials) of promising cancer preventive agents is supported by the Cancer Prevention Clinical Trials Network (CP-CTNet). The goal of this Program is to identify preliminary efficacy and safety of preventive strategies. The results of preliminary efficacy studies provide important data to inform decisions to proceed to lengthy, expensive phase III cancer prevention trials, thereby minimizing the risk of failure in phase III. This program fills a critical niche in cancer preventive drug development that is poorly supported by the pharmaceutical industry and not well represented in the investigator-initiated grants portfolio.
• The phase III cancer preventive agent development, aimed at demonstrating definitive efficacy, is supported via the NCI Community Oncology Research Program (NCORP).

This NOFO and RFA-CA-24-025 will fund the continuation of CP-CTNet. Each CP-CTNet Site will perform a variety of early phase cancer prevention trials in appropriately high-risk populations, ranging from phase 0 to phase IIb trials. Agents to be studied will include those developed by the pharmaceutical industry and provided to NCI for collaborative development, commercially available agents, agents developed by the grantees, and agents developed by NCI.

Overall Goals of CP-CTNet and Requirements for CP-CTNet Sites

The overall goal of CP-CTNet is to perform early phase cancer prevention clinical trials to identify agents and interventions that can advance through the various phases of clinical development. Specific objectives are summarized below:

• To efficiently design and conduct early phase clinical trials to assess the cancer preventive potential of a variety of different agents or strategies. Emphasis is on novel agents and interventions that target relevant pathways important in carcinogenesis.
• To characterize the effects of these agents and interventions on their molecular targets, immune function, and other biological events associated with cancer development (e.g., cell proliferation, apoptosis, growth factor expression, oncogene expression, etc.) and correlate these effects with clinical endpoints.
• To develop further scientific insights into the mechanism of cancer prevention by the agent or strategy examined and to continue to develop novel potential markers as determinants of response.
• To facilitate development and conduct of cross-network trials and to speed up preventive agent development.

Goals and Scope of Activities for CP-CTNet Sites

The main role of CP-CTNet Sites will be to design and conduct early phase (phase 0-II) cancer prevention clinical trials.

For this role, each CP-CTNet LAO will be expected to serve as the main research infrastructure to support the performance of clinical trials. The LAOs will provide administrative support and oversight to clinical trial performance across their member AOs, as well as develop and perform specific clinical trials within their own (LAO) institutions. The role of the AOs will be to develop clinical trials in collaboration with the LAOs and to accrue to specific studies. LAOs and AOs may participate in studies arising within their CP-CTNet Site as well as within other CP-CTNet Sites. Studies that are performed across CP-CTNet Sites, with funding provided by different CP-CTNet Sites, are considered cross-network trials and are encouraged.

The LAO will be required to interact closely with the DMASC, which will provide centralized data management, statistical expertise for cross-network trials, auditing, and network-wide administrative support.

Required Capabilities: Each proposed CP-CTNet Site needs to have expertise, skills, and infrastructure for the proper conduct of the following expected scope of activities:

• Designing and conducting early phase cancer prevention clinical trials using single agents, combinations of agents or other modalities. The emphasis will be on novel agents or strategies that target relevant pathways important in carcinogenesis, such as those involved in immune function, proliferation, apoptosis, differentiation, cell signaling, and others.
• Managing all aspects of study operations, including quality assurance plans, while adhering to all applicable rules and regulations for the conduct of clinical trials. This includes monitoring of all trials performed at the LAOs and AOs.
• Developing 1-3 new clinical trials per year, with expected accrual of 10-40 or more participants per year at each CP-CTNet Site. For new CP-CTNet Sites, 10 participants will be expected to be accrued in year 2, and 40 or more participants will be accrued starting with year 3. For returning CP-CTNet Sites that have ongoing clinical trials, 40 or more participants are expected to be accrued starting with year 1. 
• Conducting prevention clinical trials in participants at risk for cancers arising in one of at least 3 different target organs (at least one of which is breast, colon, prostate, or lung and at least one of which is not one of those 4 target organs), with access to populations at high risk for the development of cancer in these organs.
• Developing statistically appropriate clinical trial designs, including novel designs using ‘omic’ technologies, to rapidly obtain evidence of preliminary efficacy. A variety of clinical trial models, including phase 0 micro-dosing trials, phase I pharmacokinetic and pharmacodynamic (PK/PD) trials, window-of-opportunity trials performed prior to definitive treatment for premalignant lesions or cancer, and phase IIa or IIb cancer prevention clinical trials, will be used.
• Evaluating translational endpoints in biospecimens obtained from participants in clinical trials of investigational agents/strategies (e.g., the levels of expression and/or activity of molecular targets and/or downstream effectors pertinent to a given agent, effects on immune function).
• Assessing PK/PD of the studied agents and establishing relationships between the dose, schedule, exposure, and effect.
• Obtaining mechanistic proof-of-principle data for new agents or approaches directed at novel molecular targets important in carcinogenesis.
• Collecting, processing, and storing biospecimens from trial participants for biomarker analysis.
• Evaluating novel technologies (e.g., imaging, blood based, etc.) for assessing the effects of interventions.
• Mentoring and professional development of young/junior investigators in cancer prevention science.

Agents to be Studied: Agents to be developed will be announced quarterly via NCI solicitations for Concept Proposals for clinical trials. Agents may be developed for specific indications by individual CP-CTNet Sites or jointly by more than one Site (for cross-network trials). CP-CTNet Sites are also expected to propose unsolicited concepts using agents or interventions available to their investigators.

Important Note: It is expected that the CP-CTNet Sites supported under this NOFO will have expertise in evaluating multiple types of agents, with emphasis on pharmacologic agents and immunopreventive vaccines and other immune modulators.

Required Functional Components: To realize the stated objectives, the CP-CTNet Site applicants must organize and include the following two required functional components:

• Clinical Trial Program – This functional component must include the scientific leadership capable of developing and conducting early phase cancer prevention clinical trials within each CP-CTNet Site or across Sites within the network and the infrastructure to oversee, support, and to ensure compliance with applicable clinical trial regulations.
• Site Accrual Program – This functional component must provide robust accrual of appropriately diverse study participants at the LAO and AOs to CP-CTNet trials, including accrual to studies focusing on the identified target organ sites that give rise to less common cancers (e.g., those arising in the oral cavity, esophagus, ovary, bladder, etc.), as well as timely activation of trials and provision of good clinical trial stewardship.

CP-CTNet Network Governance and Trans-Network Activities

Steering Committee: The representatives of CP-CTNet awardees (with the participation of the NCI) will be expected to form a Steering Committee as a self-governing body for the Network. For details on the composition and responsibilities of the Steering Committee, see Section VI.2 under Cooperative Agreement Terms and Conditions of the Award.

Trans-Network Research Activities

All CP-CTNet Sites will be expected to work jointly toward the CP-CTNet network goals by:

• Collaborating with the DMASC on network activities;
• Working with other CP-CTNet Sites and the DMASC to develop cross-network trials and participating in cross-network clinical trials developed by other CP-CTNet Sites; and
• Participating in high priority ancillary studies, including developmental work for new biomarkers.

Non-responsive Applications

The following types of activities remain outside the scope of this NOFO, and applications proposing them are non-responsive to this NOFO and will not be reviewed:

•  Proposals from institutions that do not have the infrastructure to recruit participants to cancer prevention clinical trials from within their own institution.

Additional NCI Support for the Initiative (beyond the scope of the two CP-CTNet NOFOs).

NCI/DCP will provide the following additional infrastructure support to CP-CTNet participants:

• Regulatory support, including Investigational New Drug (IND) application preparation and Food and Drug Administration (FDA) reporting
• Agent acquisition, packaging, and distribution, including placebo manufacture when feasible
• Central Institutional Review Board (CIRB) review
• Protocol receipt, review, and approval process, and study document submissions and management

NCI will support data and specimen access through the Cancer Data Access System (CDAS). This portal will provide access to the CP-CTNet clinical trial data after trial publication and will provide access to request associated residual biospecimens.  NCI will provide long-term storage for the collected biospecimens. 

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)

Federal Governments

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

Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not 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 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.

The individual designated as PD/PI for the CP-CTNet Site must have his/her primary affiliation at the application-submitting institution (i.e., the LAO). For proposals with Multiple PDs/PIs, the second individual designated as MPI may have a primary affiliation at a different US institution.

These individuals are expected to be nationally and internationally recognized leaders in clinical trials of cancer preventive agents. This expertise should reflect mainly clinical trials of preventive agents (e.g., drugs, small molecules, vaccines/biologics) using measures of drug action and efficacy that include modulation of cancer-related biomarkers.

Additional expertise in other cancer preventive approaches (including medical devices, cancer preventive surgery, risk-reducing surgery, and non-surgical ablative techniques) is also desirable.

The PDs/PIs of applications submitted in response to this NOFO must not be named as Senior/Key Personnel or Other Significant Contributors on the CP-CTNet DMASC award supported under RFA-CA-24-025.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit only one application per institution

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).

Only one application per institution is allowed; the institutional resources needed to be a successful LAO and to avoid local competition for resources are too great for any one institution to be able to support more than one LAO.

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 How to Apply - 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:

Eva Szabo, MD 
National Cancer Institute (NCI)
Telephone: 240-276-7011
Fax: 240-276-7848
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.

• Research Strategy Section is limited to 30 pages

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.

Facilities & Other Resources:

In addition to the standard items for this attachment, provide the documentation of main capabilities and available resources for CP-CTNet Site. Relevant information may be provided in table form. Provide documentation on the characteristic of the scientific environment in which the cancer clinical trials and other human subjects research will be conducted. Include such aspects as:

• Characteristics of the AOs (as applicable) that will be accruing participants to CP-CTNet clinical trials. A table can be used to show such information as: the name of entity, responsible AO Site Lead, city, and state where the entity is located, target organs or special high-risk populations that the site will be studying, and access to diverse populations.
• Research pharmacy description (at LAO and AOs). Describe investigational pharmacy operations, procedures, and adherence to local/state/federal guidelines.
• Biospecimen repository storage facilities and summary of procedures for collection, processing, storage, retrieval, and dissemination of biospecimens.

SF424(R&R) Other Project Information

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

(Applicants must provide the following additional material specified below.  Each attachment should be uploaded as a separate PDF using the indicated filenames (which will serve as application bookmarks).

Attachment 1. Scientific Achievements for Clinical Trials (Use filename: Scientific Achievements): 'Scientific achievements' refers to important information from primary and secondary endpoints of previously performed clinical trials listed in Attachment 3. A table can be used to show such information as the general cancer site category, trial phase, year of publication of study primary outcome or other significant impact, brief title, investigational agent/regimen, description of endpoint or sub-study result, manuscript or abstract reference, and brief description of the importance of endpoint or sub-study result. 

For renewal applications, provide overview of major achievements specifically from prior CP-CTNet grant, as well as from other clinical trials if relevant.

Attachment 2: Sample Cancer Prevention Clinical Trial Concepts (Use filename: Sample Concepts): Provide two sample concepts for clinical trials to illustrate the team's approach to preventive agent development. These sample concepts should be realistic and feasible (e.g., the applicants should demonstrate access to agents and target populations proposed.) Although the concepts are primarily to document applicants' proficiency, they may be selected for implementation after grant award.

The two concepts should have the following features:

• Each sample concept should address a different target organ and use different agents/strategies.
• Each sample concept must be no longer than 10 pages (excluding references and letter of support from agent supplier).
• At a minimum, each concept should define/address/describe the following elements and may use NCI's CP-CTNet concept submission form found here:
  • Title (include phase of study),
  • Key personnel and performance sites (individual designated as study chair, study chair's performance site, all participating sites, other key personnel and their roles),
  • Target organ and study population,
  • Rationale/hypothesis,
  • Agents proposed (including dose, schedule, supplier, and evidence of access to agent),
  • Objectives (primary, prioritized secondary, and exploratory (as appropriate) objectives),
  • Details of Study Plan, including laboratory correlates/biomarkers, endpoints/statistical considerations, proposed sample sizes, etc.,
  • Participant recruitment capability (planned duration of accrual, expected monthly accrual rate, accrual capabilities of each performance site, including access to diverse accrual), and
  • The anticipated next steps in the development of the agent/strategy

Attachment 3. Completed and Ongoing Phase 0, I and Phase II Clinical Trials (Use filename: Early Phase Clinical Trials): List phase 0, I and II cancer prevention clinical trials that have been completed during the last 5 years or are ongoing. Trials conducted by or coordinated by the LAO (whether or not the LAO was an accruing site) as well as trials conducted by up to 3 proposed AOs should be included. A table can be used to show the following information: protocol title, trial phase, target organ, when the trial was approved or funded (month/year), when the trial was open (month/year opened - month/year closed), and total planned and achieved participant accrual. Indicate whether the LAO or any proposed AOs participated in each trial. Separately (in a separate table or a separate section in the same table), list up to ten phase I and/or II therapeutic clinical trials that have been completed during the last 5 years and any ongoing clinical trials for which significant research findings are available. The lead institution for each trial should be noted. Note: trials coordinated by the LAO or an AO, for which the LAO or that AO did not accrue participants, should also be listed and the 'coordination only' role should be noted. Additionally, if the LAO and its proposed AOs have participated in at least 5 cancer prevention trials, the inclusion of cancer treatment trials is optional.

For renewal applications: Include all CP-CTNet trials and identify them as CP-CTNet funded.

For new applications: Indicate if any of the included trials were CP-CTNet funded.

Attachment 4. Screening and Accrual Summary by Site for Phase I and Phase II Clinical Trials (Use filename: Trial Screening and Accrual): Provide additional screening and accrual information for the trials listed in Attachment 3. Specifically, indicate the number of participants screened and accrued at the LAO and at each proposed AO that participated in the trial (only provide information on institutions involved in the current grant application). A table can be used to show such information as protocol title, years during which the trial was open, number of participants screened, and number of participants accrued (broken out by individual accruing site).

Attachment 5: Trial Development, Participant Accrual and Trial Reporting for Individual Clinical Trials (Use filename: Trial Timelines): For each trial listed in Attachment 3, list actual timelines for the following specific steps in the clinical trial protocol development process: concept submission to approval (if appropriate), protocol development (from concept approval to final protocol approval, as appropriate), annual accrual rate projected and achieved, total accrual, total number of participants assessed for the primary endpoint, and time from last participant off study to manuscript publication. 

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

Personnel Costs

• Senior/Key Personnel and Other Personnel. The request under this category may include estimated costs of salary support (based on level-of-effort) for the PD(s)/PI(s), statistician, lead coordinator, and other personnel responsible for the various aspects of the clinical operation within the functional component of the Clinical Trial Program.
• A minimal effort level of 1.2 person-months is required for all designated PDs/PIs and cannot be reduced below that level during the project periods.
• Protocol Chairs and Lead Site Coordinators. Salary requests for Protocol Chairs and Lead Site Coordinators should be commensurate with the efforts needed for their expected involvement in 1-3 new protocols per year.

Costs of Clinical Trial Performance

The costs of prevention clinical trials are expected to vary depending on their complexity (e.g., short intervention in a “healthy cohort” versus a longer intervention in a cohort that requires eligibility determination via invasive biopsies). A balanced mix of simple and complex trials and resultant patient care costs should be anticipated.  The following types of costs may be requested:

• Costs associated with participant accrual and patient care costs (that are not part of standard care). The costs budgeted should assume accrual of a minimum of 40 participants per year in years 1-6 of the project period.
• Institutional costs of research that are not considered “a cost of treatment” by medical insurers, and therefore are not reimbursed by insurers (e.g., eligibility tests, performance of research biopsies, biospecimen handling and shipping, pharmacy start-up and per participant agent distribution, etc.).
• Costs for obtaining biospecimens to assess the main study endpoints (e.g., biopsies) and for analyses of primary and most important secondary endpoints (assume one primary and two secondary endpoints per typical trial). Standard costs for common analyses (e.g., immunohistochemistry) may be proposed.

Note: The actual costs of clinical trials performed by the CP-CTNet Site will be determined at the time that studies are proposed and conducted. The proposed complexity and maximum accrual of the studies that are performed will be limited by the funds available at the time the studies are proposed. The use of funds budgeted for participant accrual and endpoint analyses will be restricted until specific clinical trial protocols have received final approval from NCI.   

Travel Funds

The LAO PD(s)/PI(s) and at least three representatives from the CP-CTNet LAO and/or AOs will be required to travel to one annual investigator meeting per year in Rockville, MD (see section VI.2).

Patient Advocate and Community Engagement Support

The LAO will be required to engage patient advocates and/or a community engagement board to help with the planning, accrual of minority and underrepresented populations, and oversight of their clinical trials. Support for these activities should be listed in the budget.

Rapid Response Restricted Fund

An amount of $100,000 per year (direct costs) should be entered as "Rapid Response Restricted Fund" under the "Other Expenses" category in the Budget form for years 1-5. This Fund is intended for participant accrual to cross-network trials and/or novel biomarker development and analysis. Specific projects to use this fund will be proposed post-award and will be subject to Steering Committee approval.

The following costs should not be included in the budget:

• Costs associated with routine patient care that are reimbursable by insurance.
• Costs for alterations and renovations.
• Costs for supporting activities that will be provided by the DMASC or covered by services/functions funded directly by NCI outside of this NOFO (listed in Section I).

Budget Justification Additional Instructions:

In addition to the standard items for this attachment, provide a breakdown of the direct costs to show separate amounts for each functional unit (Clinical Trial Program and Site Accrual Program). 

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 Aim: Summarize the overall Specific Aims for the proposed CP-CTNet Site, addressing the development and conduct of early phase cancer prevention clinical trials. Include critical benchmarks for these aims (which should be in line with the requirements outlined in Section I).

Research Strategy: Organize the overall Research Strategy section with sub-sections in the specified order and follow instructions provided below. Start each sub-section with the appropriate sub-section heading.

Sub-Section A: Overview of the Proposed CP-CTNet Site

• Define the intended scientific focus for the proposed CP-CTNet Site and outline the overall strategy and approaches that the applicant team will use to develop and implement its research agenda.  Include proposed agents or strategies (minimum of 2) to be developed and target organs (minimum of 3) to be studied. Explain how the proposed agents/strategies would be developed in successive clinical trials (in studies funded by this NOFO or subsequently).
• Describe the LAO’s and AOs’ most important achievements in cancer prevention clinical trials.
• Describe the governance, organizational structure and capabilities, commitment relevant to the award, and general expertise of the senior leadership team.
• Provide an overview of the proposed operations.
• Describe plans for AO engagement to ensure their prioritization of CP-CTNet trials throughout the lifetime of the grant.
• Describe plans for mentorship and professional development of young/emerging investigators (e.g., faculty, clinical fellows, post-doctoral fellows), including opportunities to lead clinical trials. Note that $25,000 per year will be reserved for young investigator development; these funds will be administered by the DMASC (under Steering Committee stewardship) and will not be included in the Site budgets.
• Describe plans for engaging patient advocates and/or establishing a community engagement board to aid in the accrual of minority and underserved populations and describe how such input will be utilized. 

Note: Supporting documentation for this sub-section is requested under Other Attachments (Attachment 1).

Sub-Section B: Clinical Trial Program

Applicants should describe the proposed management of complex early phase cancer prevention clinical trials, including LOI development, protocol development, participant accrual, clinical trial monitoring, data and specimen management, data analysis and reporting, and compliance with regulatory statutes. The description must address (and be consistent with) the requirements of the NCI DCP Standard Operation Procedures for the conduct of prevention clinical trials.

Scientific and Administrative Leadership

• Describe the LAO's and AOs’, as appropriate, collective team strengths, expertise, and scientific leadership in development of early phase cancer prevention clinical trials. If experience is primarily in early phase cancer treatment trial development, include this as well. Note that PD(s)/PI(s) are expected to be leaders in the relevant areas of science and have documented administrative leadership experience.
• Explain how the proposed team and collaborations cover the needed range of transdisciplinary expertise. Include appropriate subspecialists (i.e., breast surgeons, dermatologists, gastroenterologists, gynecologists, otolaryngologists, pulmonologists, urologists, etc.) for the clinical care of individuals at high risk for cancer. As applicable, outline the roles of investigators/experts from other fields (oncology and/or non-oncology) in the design, conduct, and/or monitoring of clinical studies. In particular, address the trans-disciplinary needs for studies/clinical trials that will be focused on the identified target organs.
• Outline how the AOs will be involved in the Site scientific activities (e.g., committee memberships, study chair positions, training programs, etc.).
• Describe plans, including benchmarks, to ensure effective interaction, communication, and monitoring of performance within the LAO and AO sites. These plans should include, but not be limited to:
  • Actions to be taken to address failure by investigators and/or institutions to meet study timelines and objectives;
  • Contributions to clinical trial protocol development and conduct;
  • Compliance with clinical trial protocol requirements;
  • Timely submission of required data to NCI centralized clinical trial support systems;
  • Timely preparation, presentation, and publication of clinical trial results and research findings at international meetings and scientific journals.
• Describe available biostatistical expertise, including the capabilities of the team in analyses that combine clinical endpoints with sophisticated molecular analyses. (Biostatisticians with expertise and experience with these types of analyses are required as a part of the leadership team.)
• Describe pathology expertise in characterizing premalignant lesions in the disease areas of focus.

Operational Capacity

• Describe the LAO plans and strategy that will be used to develop new trial concepts. Address the following aspects:
  • Planning clinical trials in response to NCI solicitations:
  • Exploring original ideas developed by the LAO and/or AOs;
  • Selecting concepts from multiple potential ideas; and
  • Obtaining access to new agents to be used in studies proposed by the Site investigators.
• Describe how the LAO will provide oversight and coordination of study development, participant accrual, and study conduct. 
  • The description should include timelines for concept proposals and protocol development, study activation and completion, biomarker analyses, and submission of abstracts and manuscripts.
  • Include plans for study monitoring (defined as the act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, Standard Operating Procedures, Good Clinical Practice, and applicable regulatory requirements). Whereas the DMASC will be responsible for study auditing (the systematic and independent examination of trial-related activities and documents, performed on site or remotely), each LAO is responsible for study monitoring (see CP-CTNet Manual of Standard Operating Procedures). 
• Outline of plans for an internal CP-CTNet committee(s) to facilitate interactions of member site investigators, including review of progress and agent-related toxicities, establishment of priorities, and plans for future clinical trial research activities.
• Provide plans for procedures to oversee participant safety, protocol compliance, outcome and response review, and regulatory compliance.
• Describe criteria for adding new AOs and for removal of poorly functioning AOs.
• If foreign AOs are proposed, include plans to meet regulatory, drug acquisition/shipment, monitoring and translation requirements.

Note: Additional documentation (two samples of potential trial concepts) is requested under Other Attachments (Attachment 2). In addressing the bullets above, refer to these sample concepts as appropriate to illustrate specific points.

Trial Endpoint Evaluation

• Describe approach to selection of biomarker endpoints for phase 0-II trials.
• Outline team expertise in biomarker analyses, PK/PD determinations, and other molecular characterizations of clinical specimens. Delineate ability to conduct assays of frequently used cancer prevention biomarker endpoints, such as assays to measure proliferation and apoptosis, as well as various types of genomic, transcriptomic, and/or proteomic analyses that are applicable to evaluation of participant specimens.
• Describe ability to develop new laboratory assays or biomarkers to be used in fit-for-purpose assays ready to be transferred to or already implemented in Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories.
• Outline approach to and experience with acquisition, handling, storage, and shipment of biospecimens.
• Describe use of validated molecular and standard imaging capabilities as well as innovative experimental imaging techniques if available.

Sub-Section C: Site Accrual Program

Accrual and Study Conduct

• Describe access to healthy volunteers and individuals at high-risk for disease areas of focus for phase 0-II clinical trials at LAO and AOs.
• Describe the operational efficiency of trial activation and conduct by the CP-CTNet Site.
• Describe the ability of the LAO to conduct trials with proper clinical trial stewardship. This aspect may be illustrated, for example, by audit results from accrual to NCI-sponsored early phase cancer prevention or (if not previously participating in cancer prevention trials) cancer treatment clinical trials.
• Explain how the LAO will ensure the appropriate enrollment of participants across the cancer prevention trials spectrum (healthy to high-risk to early stage cancer) and in diverse populations, (e.g., racial/ethnic minorities, those of varied sexual and gender identities, and other underserved or underrepresented populations (e.g. rural poor)).
• Describe anticipated strategies for recruitment and retention, including any innovations related to accrual/recruitment/retention, and plans/milestones for corrective action.

Note: Supporting documentation for this sub-section is requested under Other Attachments (Attachments 3-5).

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

Other Plan(s): 

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

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

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

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

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

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.

Renewal applications will have ongoing studies that should be updated in the Human Subjects System (HSS). Both renewal and new applications will be designing trials with delayed onset and therefore applicants must add and complete the Delayed Onset Study record and must check the box "Anticipated Clinical Trial?"

Study Title - use: "Multiple Delayed Onset Studies"

Justification Attachment: Indicate that the clinical trials will be designed and conducted by the CP-CTNet Site during the Project Period. Each clinical trial protocol developed will be subject to approval through the standard NCI procedure that involves an initial concept submission and subsequent review.  If the concept receives approval, the next stage will be development of the full clinical trial protocol, which will be subject to review and approval by NCI prior to activation through the CP-CTNet. Although all new studies will be delayed onset, human subject protection must be addressed in the appropriate grant section.

PHS Assignment Request Form

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

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.

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

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

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

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

For this particular announcement, note the following:

The overarching goal of this NOFO is to bring novel prevention interventions into early phase clinical trials. This goal requires investigators with outstanding leadership and a strong record of conducting clinical trials, as well as a robust infrastructure. Particularly important for the clinical development of new generations of investigational cancer preventive interventions is the ability to integrate translational analyses into clinical trials and to perform additional studies, such as PK/PD analyses, and to obtain biomarker data in all participants enrolled on studies.

Essential for CP-CTNet will be the awardees' ability to work as part of a network. In this context, the important aspects are whether the applicants are capable of conducting state-of-the-art early phase prevention trials and biomarker-pilot studies covering a broad range of cancer prevention scenarios (ranging from cancer prevention in healthy individuals, through prevention efforts in high-risk sub-populations, to efforts focused on early stage cancer). Also important is the ability of applicants to work as a coherent research team to efficiently and expeditiously conduct early phase clinical trials.

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

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

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

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

Specific to this NOFO: The sample concepts (Attachment 2) should be reviewed, and specific comments are requested. Are the sample concepts addressing an important question, are they well-thought-out and are they feasible? Are the proposed biomarker endpoints informative? Are they likely to lead to further development of the proposed agent/strategy?

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 NCI, 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.

Appeals of initial peer review will not be accepted for applications submitted in response to this NOFO.

Applications will be assigned on the basis of established PHS referral guidelines. 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 NCI Board of Scientific Advisors. 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. 

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:

• 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 HHS, PHS, and NIH policies.
• Provide updates at least annually on progress in PEDP implementation. 
• Development of research strategy for early phase cancer prevention clinical trials and appropriate conduct, monitoring, and results reporting of NCI-approved trials.
• Development of an overall strategy to provide statistical expertise for effective scientific design, conduct, of clinical trials.
• Recruitment of AOs for diverse patient enrollment to CP-CTNet trials and oversight of AOs for the conduct of trials they participate in.
• Use of CP-CTNet’s common data management system including use of DCP reporting tools for adverse event reporting and risk-based central monitoring.
• Mentoring of new/junior investigators as well as patient advocates in clinical trials research/activities.
• Ensuring that all U.S. AOs are members of the NCI CIRBs and use the NCI CIRB for all CP-CTNet multi-site clinical trials.
• Provision of standard operating procedures covering all aspects of clinical trial design, trial conduct (including compliance with Good Clinical Practice (GCP) guidelines), development and compliance with data safety/monitoring plans and Data Safety Monitoring Board policy for applicable trials, and training for Clinical Research Associates (CRAs) at AOs and Study Chairs/Teams about their responsibilities for study monitoring and data management.
• Participation in the collective management of the CP-CTNet.

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.
• 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, NIH, and NCI policies and within the limits of any accepted binding NCI/NIH collaborative agreements with biotechnology and pharmaceutical partners and as governed by NCI-approved Data Sharing Plans and NCI-approved review for use of biospecimens collected in association with CP-CTNet trials.
• Recipients are allowed to accept funds from non-governmental sources to support CP-CTNet research that is not supported in part or in full by the NCI. These funds are considered “Program Income” (e.g., additional per case data management funding supplementing the NCI/DCP data management funding; support for correlative science studies that use biospecimen or image collections funded by the NCI/DCP for trials under the CP-CTNet) and must be reported under the Terms and Conditions of Award for the CP-CTNet unless they are associated with an exempted category under the NIH grant policy for program income, available at: https://grants.nih.gov/grants/policy/nihgps_2011/nihgps_ch8.htm#_Program_Income.
• All key components of the CP-CTNet must report these funds to the NCI on an annual basis (in the non-competitive Type 5 application – the annual progress report) and must indicate the clinical trial that the funds are being used to support (or other functional component if the funds are not provided to support specific trials). The Terms and Conditions of Award for all the Cooperative Agreements under the CP-CTNet define the operational principles under which the awardees must function to ensure the independence of the research conducted regardless of whether program income is or is not available for any of the awards.

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).

• Additionally, an NCI program director acting as Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

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

• Ensuring that clinical trials proposed are within the research scope of CP-CTNet.
• Evaluating and approving clinical trial concepts, protocols, and amendments of all CP-CTNet trials.
• Serving as a resource for scientific information on trial/study design.
• Working with CP-CTNet Awardees to collaboratively manage issues associated with their participating 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 CP-CTNet 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.
• Reviewing accrual and overall performance of CP-CTNet clinical trials by the site.
• Reviewing 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 CP-CTNet.
• Sponsoring strategy sessions, when indicated, to discuss specific research initiatives.
• Final review and approval of requests for use of any bio-specimens collected per the approved protocol for CP-CTNet trials.

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 awardees’ performance under the award for appropriate collection, review, and distribution of biospecimens collected in association with CP-CTNet trials.

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

Areas of Joint Responsibility include:

Steering Committee: A Steering Committee will be the governing body of CP-CTNet that will integrate the efforts of all CP-CTNet awardees and provide oversight of collaborative activities.

The Steering Committee will consist of the following voting members:

• Two representatives from each CP-CTNet awardee (i.e., from CP-CTNet Sites and from DMASC), one of whom must be the PD/PI, who will jointly have one vote for the CP-CTNet award they represent; and
• NCI Project Scientist(s), who will collectively have one vote for NCI.

The NCI Program Official will be a non-voting member of the Steering Committee.

Additional non-voting members may be added to the committee as needed.

The Steering Committee will be chaired by a PD/PI of a CP-CTNet cooperative agreement award and will be elected by the voting members of the Steering Committee.

Key responsibilities of the Steering Committee include:

• Holding quarterly meetings;
• Developing Network operating policies for the implementation by the CP-CTNet awardees;
• Approving the CP-CTNet Manual of Operations for the Network;
• Facilitating the process of joint development of appropriate early phase prevention clinical trial protocols by CP-CTNet Sites and NCI (see below);
• Reviewing and approving the studies that will use Rapid Response Restricted Funds;
• Reviewing and approving proposals for mentoring and professional development of young/junior investigators
• Developing agenda and co-organizing with the NCI the annual in-person investigator meeting to be held at NCI (https://events.cancer.gov/dcp/iscore); and
• Other programmatic responsibilities to be addressed jointly, as needed, by the CP-CTNet awardees and the NCI staff.     

Subcommittees. The Steering Committee may establish subcommittees for specific purposes (e.g., for joint development of clinical trial protocols by CP-CTNet awardees and NCI staff members, see below). The NCI Project Scientist(s) may serve on such subcommittees, as they deem appropriate. Other NCI staff members may also be involved as needed.

Joint Development of Early Phase Prevention Clinical Trial Protocols by CP-CTNet Awardees and NCI. CP-CTNet awardees will be expected to participate as active team members and work closely with the NCI on the development of appropriate clinical trial protocols.  These joint activities will include (but will not be limited to) the following aspects:

• General aspects of collaboration on study development and conduct, especially with respect to compliance with federal regulations for clinical trial research, accrual, and participation in activities related to the collective management of the CP-CTNet, as appropriate;
• Development of concepts for new clinical trials, either in response to specific concept solicitations from NCI or as unsolicited concepts developed by the LAOs or AOs.
• Meeting as frequently as needed to assure optimal study performance and to review studies performed under the CP-CTNet awards.

Note that in addition to these general rules for dispute resolution, a specific appeal process will be in place for decisions regarding approval of CP-CTNet study proposals and the types of studies supported by the CP-CTNet. 

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.

3. Data Management and Sharing

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

4. Reporting

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

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

Section VII. Agency Contacts

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

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

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

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

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

Eva Szabo, MD 
National Cancer Institute (NCI)
Telephone: 240-276-7011
Fax: 240-276-7848
Email: [email protected]

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

Amy Bartosch 
National Cancer Institute (NCI) 
OFFICE OF GRANTS ADMINISTRATION  
240-276-6375 
[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.