Data Management, Auditing, and Statistical Center (DMASC) (UG1 Clinical Trial Required) (2024)

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)

Funding Opportunity Title

Cancer Prevention Clinical Trials Network (CP-CTNet): Data Management, Auditing, and Statistical Center (DMASC) (UG1 Clinical Trial Required)

Activity Code

UG1 Clinical Research Cooperative Agreements - Single Project

Announcement Type

New

Related Notices

Funding Opportunity Number (FON)

RFA-CA-24-025

Companion Funding Opportunity

RFA-CA-24-024,UG1Clinical Research Cooperative Agreements - Single Project

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.393, 93.399

Funding Opportunity Purpose

Key Dates

Posted Date

August 12, 2024

Open Date (Earliest Submission Date)

September 30, 2024

Letter of Intent Due Date(s)

30 days prior to the application due date

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

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

Expiration Date

November 01, 2024

Due Dates for E.O. 12372

Not Applicable

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.

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

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.

Table of Contents

Part 1. Overview Information

Key Dates

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Section II. Award Information

Section III. Eligibility Information

Section IV. Application and Submission Information

Section V. Application Review Information

Section VI. Award Administration Information

Section VII. Agency Contacts

Section VIII. Other Information

Section I. Notice of Funding Opportunity Description

Purpose

This Notice of Funding Opportunity (NOFO) is intended to fund a Data Management, Auditing, and Statistical Center (DMASC) under the National Cancer Institute (NCI)-supported Cancer Prevention Clinical Trials Network (CP-CTNet). The purpose of 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 the respective NOFOs indicated below:

• CP-CTNet Sites (covered by companion NOFO, RFA-CA-24-024), whose role will be to design, perform and report the results of early phase (phase 0-2) cancer prevention clinical trials.
• 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 (this NOFO).

The CP-CTNet DMASCwill support the CP-CTNet Sites and coordinate trans-Network activities with the following specific responsibilities:

(i) Centralized data management and data reporting,
(ii) Clinical trials auditing,
(iii) Statistical support,
(iv) Administrative and logistical coordination across CP-CTNet.

To achieve these goals, the DMASC is expected to provide multi-disciplinary expertise in information technology, clinical research informatics, clinical trials auditing, clinical trials methodology and biostatistics, and operations management to support CP-CTNet activities.

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-24-024, including the specific goals and other vital details of their functioning 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 pharmaco*kinetic 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 network 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; https://ncorp.cancer.gov/).

This NOFO and RFA-CA-24-024 (for CP-CTNet Sites) will fund the continuation of CP-CTNet. The proposed DMASC (this NOFO) will replace and expand activities performed previously by the CP-CTNet Data Management, Auditing, and Coordinating Center (DMACC) (U24) (funded previously under RFA-CA-18-030).

Overall Goals of CP-CTNet

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.

Roles of CP-CTNet components:

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.

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 be responsible for support for clinical trials data management and reporting, clinical trials auditing, statistical support, and administrative and logistical coordination across CP-CTNet, as described below.

Because of the DMASC role in the Network, it is essential that the DMASC applicants are fully familiar not only with this NOFO, but also with the companion NOFO, RFA-CA-24-024, including the specific goals and requirements for the CP-CTNet Sites and other vital details of their functioning within the CP-CTNet.

DMASC Goals and Scope of Activities

Functional Areas.

The DMASC will be expected to facilitate efficient conduct of CP-CTNet clinical trials by providing support in four key functional areas:

• Centralized data management and data reporting;
• Clinical trials auditing;
• Statistical support, and
• Administrative and logistical coordination across CP-CTNet.

To achieve these goals, the DMASC should have appropriate multi-disciplinary expertise, background, skills, as well as established infrastructure for all the applicable areas of activities:

• Information technology;
• Clinical research informatics;
• Clinical trials auditing;
• Clinical trials methodology and biostatistics; and
• General administrative and logistical coordination capabilities to support CP-CTNet activities.

The main DMASC responsibilities in each of four key functional areas defined above include, but are not limited, to the following aspects:

Centralized Data Management and Data Reporting:

• Providing centralized data management for CP-CTNet clinical trials using Medidata Rave® as the NCI-designated Clinical Data Management System (CDMS) of record.The applicant is expected to create and enforce data management policies, formulate management techniques for quality data collection to ensure adequacy, integrity, and legitimacy of data, and devise and implement secure procedures for data management and analysis with attention to all technical and regulatory aspects.
• Providing data management support for tracking and improving participant accrual in CP-CTNet clinical trials bydeveloping and/or managing tools and resources for the collection, review, analysis, reporting, and quality improvement for accrual data and related information in partnership with CP-CTNet Sites and NCI staff.
• Supporting routine and ad-hoc reporting of clinical trials data to CP-CTNet Sites and to the NCI.The awardee will be expected to develop reports using pre-designed and custom formats that utilize real-time, historical, auditing, and/or analytical information.
• Developing web-services (e.g.,Representational State Transfer (REST),application programming interface (API), etc.) for system-to-system data exchange.The awardee will be expected to develop web-services using industry best practices to share clinical trial data with CP-CTNet Sites and with the NCI.
• Supporting efforts in management, tracking, and storage of biospecimens from CP-CTNet trials by maintaining a virtual biospecimen data inventory system that interfaces with CP-CTNet Sites and the DCP Biorepository Program. The awardee team will be expected to manage a centralized electronic inventory that will permit real-time remote access to status of biospecimens from CP-CTNet clinical trials.

Clinical Trials Auditing:

• Conducting independent auditing of clinical trials data and processes at all CP-CTNet LAOs and AOs to ensure that all relevantgood clinical practice (GCP) guidelines, protocol requirements, applicable regulatory requirements, federal regulations, and NIH/NCI/DCP policies are followed.
• Interacting with CP-CTNet Sites and NCI staff to identify areas for systemic and policy-level improvements in order to increase both efficiency and compliance, ensure the protection of human subjects, and enhance the quality and integrity of CP-CTNet clinical trials.

Statistical Support

• Providing statistical consultation and expertise for all CP-CTNet trials
• Serving as primary statisticians of record for all cross-network clinical trials and providing support to CP-CTNet LAOs and AOs

Administrative and Logistical Coordination:

• The DMASC will provide support for administrative and logistical coordination across CP-CTNet operations. The applicant will establish and maintain a unified and coordinated operational structure, including processes and documentation that appropriately support and integrate the logistical and administrative requirements of CP-CTNet.
• The DMASC will provide support for the development, presentation, and dissemination of educational materials and other capacity building resources for CP-CTNet recruitment and retention activities.

Required Functional Components:To realize the stated objectives, the CP-CTNet DMASC applicants must plan for organizing the following four required functional components:

• Data Management and Reporting Unit– This functional component must encompass experienced personnel providing support and leadership for activities in data management, data reporting, and web-services via management and coordination with teams of information technology and healthcare professionals at all levels. The emphasis is a team approach for efficient data management and reporting/data exchange functions in support of CP-CTNet clinical trials.
• Clinical Trials Auditing Unit– This functional component must encompass activities and personnel to conduct remote/virtual and on-site auditing of clinical trials data and processes for all CP-CTNet LAOs and AOs, in compliance withgood clinical practice and applicable regulatory requirements, federal regulations, and NIH, NCI and DCP policies.
• Statistical Unit– This functional component must encompass activities and personnel to provide statistical expertise and consultation for all CP-CTNet trials and serve as the primary statisticians of record for all cross-network clinical trials in support of CP-CTNet LAOs and AOs.
• Administrative and Logistical Coordinating Unit- This functional component must encompass activities that establish and maintain a unified and coordinated operational structure, including processes and documentation to appropriately support and integrate the logistical, administrative, and resource development requirements of CP-CTNet.

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

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

• Collaborating on network activities;
• Working with network collaborators to develop cross-network clinical trials; 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 that do not cover each of the four functional areas of DMASC activities, viz., data management and reporting, clinical trials auditing, statistical support, and administrative and logistical coordination.

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.

Section II. Award Information

Funding Instrument

Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed

New

Clinical Trial?

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

Funds Available and Anticipated Number of Awards

NCI intends to commit $3,250,000 (total costs) each year for 6 years beginning in FY2025 to support one award for the CP-CTNet DMASC.

Award Budget

The requested budget must not exceed $2,000,000 in direct costs in any single year.

Award Project Period

All applicants should request a 6-year project period.

Section III. Eligibility Information

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Government

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

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 theirGrants.gov registration; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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

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

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

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 DMASC must have their primary affiliation at the application-submitting institution. 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 management and stewardship of network-based/multicenter clinical trials. Their expertise should broadly encompass the four functional areas of DMASC activities, viz., data management and reporting, clinical trials auditing, statistical support, and administrative and logistical coordination. It is expected that the PDs/PIs lead a multi-disciplinary team comprised of domain-specific experts with substantial experience in leading each of the four functional areas of the CP-CTNet DMASC.

The PDs/PIs of applications submitted in response to this NOFO must not be named as Senior/Key Personnel or Other Significant Contributors on any teams submitting applications to the companion NOFO, RFA-CA-24-024.

2. Cost Sharing

This NOFO does not require cost sharing as defined in theNIH 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 theHow to Apply - Application Guideexcept 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
Telephone: 240-276-7011
Fax: 240-276-7848
Email: szaboe@mail.nih.gov

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

, with the following exceptions or additional requirements:

For this specific NOFO, the Research Strategy section is limited to 30 pages.

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

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

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

Other Attachments: 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. Completed and Ongoing Data Management and Reporting Projects (Use filename: Data Management Projects): List all ongoing and completed data management and reporting projects that the applicant team has led and coordinated during the last 5 years. A table can be used to show such information as project title, data management scope, data reporting scope, years project was/is open, and additional columns for significant and relevant project outcomes.

Attachment 2. Completed and Ongoing Clinical Trials Auditing Projects (Use filename: Auditing Projects): List all ongoing clinical trials auditing projects as well as those completed during the last 5 years. Projects conducted by or coordinated by the DMASC applicant institution(s) as well as projects conducted by affiliated organizations should be included. A table can be used to show such information as project title, focus area/organ system and phase of clinical trials, types/frequency/duration of auditing, years project was/is open, and additional columns for significant project outcomes.

Attachment 3. Completed and Ongoing Statistical Support Projects (Use filename: Statistical Projects): List all ongoing statistical support projects as well as those completed during the last 5 years. Projects conducted by or coordinated by the DMASC applicant institution(s) as well as projects conducted by affiliated organizations should be included. A table can be used to show such information as project title, focus area/organ system and phase of clinical trials, nature/scope of statistical support, years project was/is open, and additional columns for significant project outcomes.

Attachment 4. Completed and Ongoing Multi-Site Coordination Projects (Use filename: Coordination projects): List all ongoing network/multi-site trial coordination projects as well as those completed during the last 5 years. Projects conducted by or coordinated by the DMASC applicant institution(s) as well as projects conducted by affiliated organizations should be included. A table can be used to show such information as project title, focus area/organ system and phase of the clinical trial network/multi-site trial, scope of coordination activities, years project was/is open, and additional columns for significant project outcomes.

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.

Important Note on Budget: The requested budget for the DMASC should not include costs for standardized central operational, regulatory, and administrative support provided by the NCI or existing NCI Contractors (details provided at http://prevention.cancer.gov/cp-ctnet) or the tasks/activities to be performed by the CP-CTNet Sites (LAOs/AOs) as defined in the companion RFA-CA-24-024.

Personnel Effort

• PD/PI Effort Commitment. A minimum effort level of 1.8 person-months is required for the designated DMASC contact PD/PI. In case of a multi-PDs/PIs application, each PD/PI will be required to commit a minimum of 1.2 person-months. This level cannot be reduced during the project period.
• DMASC Functional Unit Directors. It is anticipated that individuals serving as DMASC Functional Unit Directors will commit substantial efforts (e.g., minimum 1.2 person-months) to this role.

DMASC Functional Units

• Data Management and Reporting Unit: The budget should be presented under the following categories:
  • Costs for hosting, maintaining, and providing round-the-clock access for an instance of Medidata Rave as the Clinical Data Management System (CDMS) of record (the license and specifications for the CDMS will be provided by the NCI).
  • Costs for the various activities described in the Research Plan including, but not limited to, the development of data management policies, formulating management techniques for quality data collection to ensure adequacy, integrity and legitimacy of data, and devising and implementing secure procedures for supporting clinical trials data management and analysis with attention to all technical and regulatory aspects, developing reports to perform clinical trial oversight, data review and/or program support, and end-of-study data collection and reporting requirements for the final study closeout process.
  • Costs for developing web services to exchange data between systems to assist with knowledge transfer and/or portfolio management, and for regulatory reporting.
  • Costs for plans to provide data management and reporting support for NCI's efforts in tracking and improving participant accrual in CP-CTNet clinical trials (DCP’s Accrual Quality Improvement Program, AQuIP).
  • Costs for maintaining a virtual biospecimen inventory system for CP-CTNet that interfaces with CP-CTNet Sites and the DCP Biorepository Program.
• Clinical Trials Auditing Unit:The budget should cover the followingtypes of costs: Costs for performing independent audits and distributing reports for all CP-CTNet clinical trials accruing sites with the following frequency:
  • LAOs will be audited on-site annually, and as needed, remotely.
  • All AOs will be audited once they have accrued 3 or more participants for a given clinical trial.
  • For intermediate and low-risk trials (e.g., FDA approved agent, over the counter medication or supplement, agent with low toxicity profile), follow-up audits will be conducted every 3 years on >50%of AOs meeting the accrual threshold (?3 participants).Site selection criteria may include but not be limited to protocol and data entry compliance, stable site staff, past audit performance rating, etc.
  • For high-risk trials (e.g., first in human trial, trial with moderate toxicity expected and/or post-administration observation period required, etc.), follow-up audits for all AOs will be conducted at least every three years, or more frequently as determined by DCP.
  • Expected ‘for-cause’ on-site auditing may be conducted on an ad hoc basis.
  • Note: remote audits may be considered in specific instances, with DCP concurrence
• Statistical Support Unit:The budget should cover the followingtypes of costs:
  • Personnel support and related costs for providing statistical expertise and consultation for all CP-CTNet trials
  • Personnel costs for serving as primary statisticians on the record for all cross network clinical trials in support of CP-CTNet LAOs and AOs.
• Administrative and Coordinating Unit:The budget should include costs for thefollowing activities:
  • Personnel support for coordination and standardization of CP-CTNet operational activities.
  • Costs for development and maintenance of documents, website content, and other educational and training materials
  • Costs for hosting leadership conference calls every two months, ad hoc conference calls, Steering Committee meetings
  • Costs for providing logistical and administrative support (e.g. web registration, on-site logistics support, etc.) for the CP-CTNet annual in-person meeting and other meetings as required.
  • Travel funds for DMASC personnel to travel to one annual investigator meeting per year in Rockville, MD (see section VI.2)

Restricted Funds for Support of Young/Emerging Investigators

An amount of $125,000 per year (direct costs) should be entered as "Restricted Funds" under the "Other Expenses" category in the Budget form for years1-5. These funds are intended for mentorship and professional development of young/emerging investigators at the CP-CTNet Sites (e.g., faculty, clinical fellows, post-doctoral fellows), including opportunities to lead clinical trials. Although investigators will be affiliated with CP-CTNet Sites, the funds will be administered by the DMASC, with a budget of $25,000 per year reserved per CP-CTNet Site, with details not known at the time of application for this NOFO. Specific projects to use these funds 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 activities to be provided by the CP-CTNet Sites 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 of the DMASC (i.e., Data Management and Reporting Unit, Clinical Trials Auditing Unit, Statistical Support Unit, Administrative and Logistical Coordinating Unit), and the amount allocated to the Restricted Funds.

R&R Subaward Budget

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

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

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

Specific Aims: Describe the overall Specific Aims for the proposed CP-CTNet DMASC addressing the applicant's goals for providing support for centralized data management and reporting, clinical trials auditing, statistical support, and coordination of operations and activities across CP-CTNet.

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

Subsection A: DMASC Overview and Capabilities

• Provide an overview of the proposed DMASC in the context of its role in the CP-CTNet and its primary responsibilities identified in Section I, indicating how DMASC can facilitate and enhance clinical trials conducted across CP-CTNet.
• Highlight any unique approaches of the proposed DMASC that reflect innovative ways of coordinating multi-institutional, trans-disciplinary, clinical trials research.
• Without repeating information in individual Biosketches and Facilities and Other Resources, summarize the collective capabilities of the applicant team, recent accomplishments, etc., in areas vital to the role of DMASC, including (but not limited to) all the aspects listed below:
  • Demonstrate ability to handle and manage multi-institutional clinical trials data, including the use of cancer-relevant common data elements (CDEs), standardized procedures for data collection, data quality control/quality assurance, etc.
  • Demonstrate ability to provide data management support for targeted clinical trials enhancement initiatives such as accrual tracking, biospecimen data management, etc.
  • Demonstrate ability to provide data reporting and web-services.
  • Outline ability to plan, manage, and implement multi-stage clinical trials auditing implementation frameworks.
  • Demonstrate ability to provide statistical consultation and expertise and design and implement statistical analysis plans as the lead statistician(s) on cross-network, multi-center clinical trials
  • Outline coordination and organizational support for multi-institutional and multi-disciplinary collaborative research efforts
  • Describe how the four key required DMASC Functional Units (plans for which will be described in Subsections B-F below) will contribute to aspects, attributes, and functions of CP-CTNet identified in Section I. The description must address (and be consistent with) the requirements of the NCI DCP CP-CTNet Standard Operation Procedures (https://prevention.cancer.gov/clinical-trials/clinical-trials-management/cp-ctnet-instructions-forms-and-templates) for the conduct of prevention clinical trials.

Note: Supporting documentation for this sub-section is requested under Other Attachments (Attachments 1-4).

Subsection B: Data Management and Reporting Unit:

Describe proposed approach and plans for efficient management of clinical trials data collected within CP-CTNet. Specifically, address support activities for the following:

1. Management of Clinical Trials Data

Describe plans for creating and enforcing data management policies, formulating management techniques for quality data collection to ensure adequacy, integrity and legitimacy of data, and devising and implementing secure procedures for clinical trials data management and analysis with attention to all technical and regulatory aspects. These should specifically address the following:

• General description for hosting and maintaining an instance of Medidata Rave as the Clinical Data Management System (CDMS) of record. The license and specifications for the CDMS will be provided by the NCI. (Additional information can be found at http://prevention.cancer.gov/cp-ctnet.)
• Procedures to ensure that the system is available 7 days per week with minimum interruptions to reduce the risk of data loss and disruption of operations.
• Procedures to ensure all CDMS systems and modules involving clinical trials data comply with Part 11 of Title 21 of the Code of Federal Regulations: Electronic Records; Electronic Signatures;
• Plans for data management activities including but not limited to CDMS study build tasks to develop and/or maintain standardized and study-specific eCRFs. NCI-defined common data elements (CDEs) and other CDMS elements should be utilized to ensure data consistency, quality and integrity across studies.
• Data standards and clinical data requirements to be defined and established for CP-CTNet clinical trials
• Procedures for the electronic transfer of data that meet or exceed the NIH and NCI data security standards and guidelines.
• Education and training required for the efficient use of Medidata Rave or other databases by CP-CTNet and NCI staff as needed.
• System set-up and integration with other NIH, NCI and DCP systems. (Additional information can be found at http://prevention.cancer.gov/cp-ctnet.)
• Ad hoc support for AQuIP data reports and/or graphs, or other data support for presentations, manuscript preparation, and other publications.

2. Routine and Ad-hoc Reporting of Clinical Trials Data

Outline plans for developing reports to perform clinical trial oversight, data review and/or program support, by addressing the following:

• Development and/or maintenance of standard operating procedures for clinical trials data reporting, including but not limited to transfer of data captured from Medidata Rave or other databases to DCP monthly, bi-annually, and ad-hoc. (Additional information can be found at http://prevention.cancer.gov/cp-ctnet.)
• Provide routine and ad-hoc reports to assess data quality, timeliness and completeness, assist in the resolution of data discrepancies, and present pertinent clinical trial information to CP-CTNet and NCI staff.
• Support of end-of-study data collection and reporting requirements for the final study closeout process. (Additional information can be found at http://prevention.cancer.gov/cp-ctnet.)

3. Development of Web-Services

Outline plans for developing web services to exchange data between systems to assist with knowledge transfer and/or portfolio management, by addressing the following:

• Development of web-services (e.g., Representational State Transfer (REST), application programming interface (API), etc.) for system-to-system data exchange using industry best practices to exchange clinical trial data.
• Development and implementation of web-services for NCI to receive electronic transfer of standardized dataset from Medidata Rave or other databases to assist NCI with complying with NIH and/or other Federal-level data reporting requirements. (Additional information can be found at http://prevention.cancer.gov/cp-ctnet.)

4. Data Management for Accrual Tracking

Describe plans for providing data management support for NCI's efforts in tracking and improving participant accrual in CP-CTNet clinical trials.

• Develop and/or maintain tools, system(s), and processes for the collection, review, analysis, and reporting of per-person accrual and related information for clinical trials in partnership with CP-CTNet performance sites.
• Provide data management and reporting support for NCI's efforts in tracking and improving participant accrual in CP-CTNet clinical trials (via DCP’s Accrual Quality Improvement Program (AQuIP).

5. Virtual Biospecimen Inventory System for Clinical Trials

Describe plans for supporting NCI's efforts in management, tracking, and storage of biospecimens from CP-CTNet clinical trials.

• Outline plans for developing and maintaining a virtual biospecimen inventory system for CP-CTNet that interfaces with CP-CTNet Sites and the DCP Biorepository Program. The plan should include the approach for a seamless and secure transfer of the virtual biospecimen data/inventory from the current U24 DMACC grantee. (Additional information can be found at http://prevention.cancer.gov/cp-ctnet.).
• The virtual inventory system should include standard clinical and specimen annotations and study-specific information and should have remote (web-based) real-time access functionality.

Subsection C: Clinical Trials Auditing Unit:

Describe plans and approaches for audits of all CP-CTNet Sites that DMASC will be required to perform as an entity outside of the audited sites. The plans should ensure that all clinical trial-related activities CP-CTNet Sites are in compliance with federal regulations, protocol requirements, GCP guidelines, and NIH, NCI and DCP policies, procedures and requirements for protocol and clinical trials development, implementation and management. The plans need to accommodate the following required to audit frequency:

• LAOs will be audited on-site annually, and as needed, remotely.
• All AOs will be audited once they have accrued 3 or more participants for a given clinical trial.
• For intermediate and low-risk trials (e.g., FDA approved agent, over the counter medication or supplement, agent with low toxicity profile), follow-up audits will be conducted every 3 years on >50%of AOs meeting the accrual threshold (?3 participants). Site selection criteria may include but not be limited to protocol and data entry compliance, stable site staff, past audit performance rating, etc.)
• For high-risk trials (e.g., first in human trial, trial with moderate toxicity expected and/or post-administration observation period required, etc.) follow-up audits for all AOs will be conducted at least every three years, or more frequently as determined by DCP.
• Expected ‘for-cause’ on-site auditing may be conducted on an ad hoc basis.
• Note: remote audits may be considered in specific instances, with DCP concurrence

Outline plans for inspecting and auditing CP-CTNet Sites, including, but not limited to, the following activities:

• Develop and/or update as well as implement processes, procedures and documentation for clinical trials auditing of all CP-CTNet Sites;
• On-site or remote auditing of all CTNet Sites to ensure data quality and site compliance with federal regulations, GCP Guidelines, NCI and NIH policies and procedures, and DCP's protocol, regulatory, pharmacy, and data collection requirements (additional information can be found at http://prevention.cancer.gov/cp-ctnet);
• Preparation and distribution of reports of audit visit findings and follow-up of visit action items for NCI DCP review and approval and dissemination to the appropriate LAOs.
• Engage with CP-CTNet Sites and NCI staff to identify areas for systemic and policy-level improvements in order to increase both efficiency and compliance, ensure the protection of human subjects, and enhance the quality and integrity of CP-CTNet clinical trials.

Subsection D: Statistical Support Unit:

Describe proposed approach and plans for providing statistical support for clinical trials data collected within CP-CTNet. Specifically, address support activities for the following:

• Providing independent and authoritative statistical consultations to CP-CTNet constituents for network clinical trials
• Overview of plans to serve the function as the primary statistician(s) of record for all cross-network clinical trials in support of LAOs and AOs in CP-CTNet

Subsection E: Administrative and Coordinating Unit:

Explain how this unit will provide support for administrative and logistical coordination across CP-CTNet operations. Describe plans that include, but are not limited to, the following activities:

• Coordination and standardization of CP-CTNet operational activities across all CTNet Sites, by establishing and maintaining a unified and coordinated operational structure, including processes and documentation that appropriately support and integrate the logistical and administrative requirements of CP-CTNet.
• Development and maintenance of documents, such as the DMASC Manual of Operations, CP-CTNet standard operating procedures, website content for CP-CTNet, and other procedural documents and materials.
• Logistical and administrative support for leadership conference calls every two months, ad hoc conference calls, Steering Committee meetings, annual in-person meeting, and other meetings as required.
• Development, presentation, and dissemination of educational and training content and tools to support clinical and CP-CTNet operations at all CTNet Sites.
• Tools, training, educational materials and other capacity building resources to support timely recruitment to clinical trials at all CP-CTNet Sites.
• Support for the CP-CTNet DSMB meetings, including honoraria for DSMB members (n=5) for yearly remote meetings
• Other operational and administrative support, as needed.

Subsection F: Transition:

Describe a transition plan that will ensure the continuity of all services outlined in this NOFO subsections A-E. The transition plan shall demonstrate a seamless approach of all tasks, systems, URLs, material, data, and other documents securely.

(Additional information can be found at http://prevention.cancer.gov/cp-ctnet.)

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 theHow 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.

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

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.

Applications 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 Sites with NCI assistance 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. The DMASC will participate as a CP-CTNet clinical trial infrastructure during the implementation of the approved clinical trials.

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

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 theHow to Apply – Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

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 theNIH 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.

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

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

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.

Overall Impact

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

Scored Review Criteria

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

Significance

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

Investigator(s)

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

Innovation

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

Approach

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

Does the application adequately address the following, if applicable

Study Design

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

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

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

Data Management and Statistical Analysis

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

Specific for this NOFO:

• How adequate is the proposed plan for centralized data management and reporting, clinical trials auditing, and administrative and logistical coordination for support of multi-institutional research and collaboration within CP-CTNet? How adequate are plans for providing data management support and developing and managing tools, system(s) and processes for NCI's efforts in tracking and improving participant accrual in CP-CTNet clinical trials? To what extent are the proposed leadership and governance structure, staffing, decision-making processes, and interactions among key personnel optimal for supporting the goals of CP-CTNet?
• How adequate are plans for seamless and secure transition of the CP-CTNet Rave URL, databases, and associated information including the AQuIP system currently being hosted and maintained by the current U24 grantee (i.e., code, database, and/or other AQuIP materials)?
• How adequate are the plans for developing web services to exchange data between systems to assist with knowledge transfer and/or portfolio management and to assist in complying with data reporting requirements?
• How adequate are plans for development and maintenance of the virtual biospecimen inventory system and do the plans include an approach for a seamless and secure transfer of the virtual biospecimen data/inventory from the current U24 grantee?
• How adequately do the plans for independent audits of all CP-CTNet Sites as part of the plan for the functional unit focused on Clinical Trials Auditing address the needs outlined in this NOFO?
• How adequate are the plans for providing statistical expertise and consultation for all CP-CTNet trials and serving as the primary statisticians of record for all cross-network clinical trials in support of CP-CTNet LAOs and AOs?
• How adequately are plans and approaches for providing support for administrative and logistical coordination across CP-CTNet operations described, plans for the development and maintenance of network coordination documents, such as the DMASC Manual of Operations, CP-CTNet standard operating procedures, website content for CP-CTNet, and other procedural documents and materials described? How adequate are plans for the development, presentation, and dissemination of educational and training content and tools to support clinical and CP-CTNet operations and clinical trial recruitment at all CP-CTNet Sites described?
• How adequately does the proposed DMASC organization adequately facilitate (a) the application of novel methodologies and analytics related to data harmonization and the creation of integrated datasets; (b) data management in the context of multi-institutional and interdisciplinary studies; (c) cancer prevention agent development science; (d) appropriate and required privacy and confidentiality protections; (e) regulatory compliance and (g) reuse of data? How strong are the applicant's measures to protect data confidentiality, prevent data loss or data security breaches, and overcome other concerns related to data safety and security?

Environment

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

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

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

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

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Additional Review Criteria

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

Study Timeline

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

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Biohazards

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

Select Agent Research

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

Resource Sharing Plans

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

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

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

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

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

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via theeRA 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 theNIH 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 inSection 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 theNIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, seeAward 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 theHHS 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 inNIH 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 circ*mstances. See2 CFR Part 200.340 Termination andNIH 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.
• Managing the DMASC’s operations and tasks, including but not limited to data management and reporting, clinical trials auditing, statistical support, and administration and coordination of the CP-CTNet.
• Managing a centralized clinical trial data management system to support CP-CTNet trials including coordinating and leveraging, where feasible, NCI’s Common Data Elements.
• Protecting the confidentiality of CP-CTNet clinical trial data and the information shared with CP-CTNet organizations, including, without limitation, unpublished data, protocols, data analysis, and other confidential information received by CP-CTNet personnel.
• Providing routine and ad-hoc reports and data to CP-CTNet and NCI.
• Developing and supporting the end of study data collection and reporting requirements.
• Developing and/or maintaining a clinical trials accrual quality improvement program and accrual tracking system.
• Developing and maintaining a virtual biospecimen inventory system to support tracking the collection and use of the biospecimens and related data.
• Providing expertise in statistical design and analysis for cross-network trials as the primary statistician of record
• Serving as a resource for consultations on statistical design and analysis for all CP-CTNet trials
• Developing and maintaining procedural documents and materials for logistical and administrative support of CP-CTNet.
• Establishing collaborations among the DMASC team, CP-CTNet, and other NCI support organizations.
• Establishing project timelines in coordination with NCI to ensure all required DMASC activities are adequate and developing standard operating procedures in support of CP-CTNet operations and management.
• Participating in the collective management of the CP-CTNet including the internal evaluation of the CP-CTNet program.
• Coordinating with and leveraging, where feasible, technology from related NCI-sponsored informatics initiatives, e.g. the NCI Informatics Technology for Cancer Research (ITCR) program, and the NCI Cancer Research Data Commons (cbiit.cancer.gov/cancerdatacommons). Additional information regarding this can be found at http://prevention.cancer.gov/cp-ctnet.

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 plans for data management, data reporting, auditing, and coordination of clinical trials proposed are within the research scope of CP-CTNet and relevant to the state-of-the-science, NIH/NCI priorities, resources, and availability of funding;
• Serving as a resource for best practices for data management, data reporting, and clinical trials auditing;
• Overseeing and participating as necessary in clinical trials audits and quality assurance site visits (on-site and remote) and reviewing audit reports;
• Working with CP-CTNet Awardees to collaboratively manage scientific, administrative, and implementation issues associated with their participation in the conduct of clinical trials across CP-CTNet;
• Informing the CP-CTNet awardee PD(s)/PI(s) 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 at CTNet Sites;
• Reviewing compliance with applicable HHS, FDA, OHRP, NIH, and NCI regulations for clinical research involving human research subjects; and
• 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 biospecimens collected per the approved protocol for CP-CTNet trials.

The NCI will have access to all raw data (including imaging data) from clinical trial participants 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 CP-CTNet trials.

The NCI reserves the right to reduce the budget or withhold an award in the event of substantial awardee underperformance 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 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 protocol. 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.

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 theResearch 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.

Section VII. Agency Contacts

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

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email:GrantsInfo@nih.gov(preferred method of contact)
Telephone: 301-480-7075

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

Section VIII. Other Information