It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. 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

This Funding Opportunity Announcement (FOA) is one of two FOAs for 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 FOAs indicated below:

• CP-CTNet Sites (covered by companion FOA, RFA-CA-18-029), whose role will be to design, perform and report the results of early phase (phase 0-2) cancer prevention clinical trials.
• CP-CTNet Data Management, Auditing, and Coordinating Center (DMACC) (this RFA).

The CP-CTNet DMACC will 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, and

(iii) administrative and logistical coordination across CP-CTNet.

To achieve these goals, the DMACC 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 FOA:

• The terms Clinical Research and Clinical Trials in this FOA follow the NIH definitions (https://grants.nih.gov/policy/clinical-trials/glossary-ct.htm#ClinicalResearch.)
• CP-CTNet Site: UG1 Consortium supported by RFA-CA-18-029 consisting of 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 participants in the trial should be at high risk for developing cancer arising in the 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.

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 prospect of an even better understanding of the early phases of cancer development, such as will be provided by the Pre-Cancer Atlas (https://grants.nih.gov/grants/guide/rfa-files/rfa-ca-17-035.html), provides a strong rationale for increased investment in cancer prevention. Similarly, 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 immunoprevention. The increasing number and molecularly or immunologically targeted nature of new agents require an efficient clinical trials system for evaluation and screening. 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 procedures such as a colonoscopy or bronchoscopy to identify those who harbor such premalignancies, followed by post-treatment procedures with biopsies to assess the intervention’s efficacy. Other types of studies employed in cancer preventive agent development include (but are not limited to): phase 0 micro-dosing trials, phase I pharmacokinetic and pharmacodynamic trials, and window-of-opportunity trials performed prior to definitive cancer treatment. Cohorts 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 surgical, radiation, or chemoradiation treatment. 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 programs managed by the Division of Cancer Prevention (DCP):

• Preclinical agent development is supported through the PREVENT Cancer Preclinical Drug Development Program (https://prevention.cancer.gov/major-programs/prevent-cancer-preclinical).
• The early phase clinical development (phase 0-II clinical trials) of promising cancer preventive agents has been primarily supported by the contract-funded Phase 0-II Cancer Prevention Clinical Trials Program (Phase 0/I/II Cancer Prevention Clinical Trials Program). The goal of this program is to identify preliminary efficacy and safety of preventive strategies. The results of preliminary efficacy studies provide important data to inform decisions to proceed to lengthy, expensive phase III cancer prevention trials, thereby minimizing the risk of failure in phase III. This program fills a critical niche in cancer preventive drug development that is poorly supported by the pharmaceutical industry and not well represented in the investigator-initiated grants portfolio.
• The phase III cancer preventive agent development, aimed at demonstrating definitive efficacy, is supported via the NCI Community Oncology Research Program (NCORP; https://ncorp.cancer.gov/).

The CP-CTNet, as funded by the NCI through RFA-CA-18-029 and this FOA, will replace the current contract-funded Phase 0-II Cancer Prevention Clinical Trials Program.

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, as well as on other biological events associated with cancer development (such as cell proliferation, apoptosis, growth factor expression, oncogene expression, immune response) 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.

Roles of CP-CTNet components:

CP-CTNet Sites will perform a variety of early phase cancer prevention trials in appropriately high-risk populations, ranging from phase 0 to phase IIb trials. Agents under study 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.

The CP-CTNet Data Management, Auditing, and Coordinating Center (DMACC) will be responsible for support for clinical trials data management and reporting, clinical trials auditing, and administrative and logistical coordination across CP-CTNet as described below.

Because of the DMACC role in the Network, it is essential that the DMACC applicants are fully familiar not only with this FOA, but also with the companion FOA, RFA-CA-18-029, including the specific goals and requirements for the CP-CTNet Sites and other vital details of their functioning within the CP-CTNet.

DMACC Goals and Scope of Activities

Functional Areas. The DMACC will be expected to facilitate efficient conduct of CP-CTNet clinical trials by providing support in three key functional areas:

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

To achieve these goals, the DMACC 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 DMACC responsibilities in each of three key functional areas defined above include, but are not limited, to the following aspects:

Centralized Data Management and 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 by developing and 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.
• Development of 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 exchange clinical trial data to CP-CTNet Sites and to the NCI.
• Supporting efforts in management and storage of biospecimens from CP-CTNet trials by developing and 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 develop and 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 relevant good 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.

Administrative and Logistical Coordination:

• The DMACC 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 DMACC 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 DMACC applicants must plan for organizing the following three 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 managing and coordinating 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 with good clinical practice and applicable regulatory requirements, federal regulations, and NIH, NCI and DCP policies.
• 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 CP-CTNet DMACC will be expected to establish productive collaborations with CP-CTNet’s Lead Organizations (LAOs) and Affiliated Organizations (AOs) and facilitate interactions across CP-CTNet Sites and NCI staff in support of CP-CTNet clinical trials and high priority ancillary studies, including developmental work for new biomarkers.

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

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
• Central Institutional Review Board (CIRB) review
• Protocol receipt, review, and approval process, and study document submissions and management

NCI anticipates providing long-term storage solutions for the collected biospecimens and access to them for the research community.

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

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

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:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o 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)

Governments

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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.

• System for Award Management (SAM) (formerly CCR) 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.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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 DUNS number and 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 his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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

Any individual(s) designated as PD(s)/PI(s) for the CP-CTNet DMACC must have their primary affiliation at the application-submitting 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 three functional areas of DMACC activities, viz., data management and reporting, clinical trials auditing, 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 three functional areas of the CP-CTNet DMACC.

The PDs/PIs of applications submitted in response to this FOA must not be named as Senior/Key Personnel or Other Significant Contributors on any teams submitting applications to the companion FOA, RFA-CA-18-029.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit only one application per institution (normally identified by having a unique DUNS number or NIH IPF number)

The NIH will not accept duplicate or highly overlapping applications under review at the same time. 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 NOT-OD-11-101).

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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 SF424 Application Guide and the Table of Page Limits must be followed

Research Strategy Section is limited to 30 pages

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

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

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

All instructions in the SF424 (R&R) Application Guide must be followed. Additional instructions are defined below.

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

All instructions in the SF424 (R&R) Application Guide must be followed. The following additional guidance applies.

Important Note on Budget: The requested budget for the DMACC 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-18-029.

Personnel Effort

• PD/PI Effort Commitment. A minimum effort level of 1.8 person-months is required for the designated DMACC 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.
• DMACC Functional Unit Directors. It is anticipated that individuals serving as DMACC functional Unit Directors will commit substantial efforts (e.g., minimum 1.2 person-months) to this role.

DMACC Functional Units

• Data Management and Reporting: 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.
• Costs for developing and 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 following types of costs:
• Costs for performing independent audits and distributing reports for all CP-CTNet clinical trials accruing sites with the following frequency:

o LAOs will be audited on-site annually, and as needed, remotely.

o AOs will be audited remotely on an annual basis, or on-site in the following instances: the AO has accrued 10 or more participants across all studies in the previous 12 months, or three years have elapsed since the AO’s last on-site audit.

o Expected for-cause on-site auditing that may be conducted on an ad hoc basis.

• Administrative and Coordinating Unit: The budget should include costs for the following 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 DMACC personnel to travel to one annual investigator meeting per year in Rockville, MD (see section VI.2)

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 FOA (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 DMACC (i.e., Data Management and Reporting Unit, Clinical Trials Auditing Unit, Administrative and Logistical Coordinating Unit).

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

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

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aim: Describe the overall Specific Aims for the proposed CP-CTNet DMACC addressing the applicant's goals for providing support for centralized data management and reporting, clinical trials auditing, 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: DMACC Overview and Capabilities

• Provide an overview of the proposed DMACC in the context of its role in the CP-CTNet and its primary responsibilities identified in Section I, indicating how DMACC can facilitate and enhance clinical trials conducted across CP-CTNet.
• Highlight any unique approaches of the proposed DMACC 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 DMACC, including (but not limited to) all the aspects listed below:
• 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.
• Ability to provide data management support for targeted clinical trials enhancement initiatives such as accrual tracking, biospecimen data management, etc.
• Ability to provide data reporting and web-services.
• Ability to plan, manage, and implement multi-stage clinical trials auditing implementation frameworks.
• Coordination and organizational support for multi-institutional and multi-disciplinary collaborative research efforts
• Describe how three key required DMACC Functional Units (plans for which will be described in Subsections B-D 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 Standard Operation Procedures (https://prevention.cancer.gov/clinical-trials/clinical-trials-management/2012-consortia-early-phase) for the conduct of prevention clinical trials.

Note: Supporting documentation for this sub-section is requested under Other Attachments (Attachments 1-3).

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 implement 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.)

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 implementation of standard operating procedures for clinical trials data reporting, including but not limited to 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.)
• Development of 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.
• Development and 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 U24 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 manage 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.
• Participate in the transition of the existing accrual quality improvement and tracking program in the ongoing contract-funded Phase 0-II Cancer Prevention Clinical Trials Program, including but not limited to the transfer of data and materials to new systems as required. (Additional information regarding the existing accrual quality improvement program can be found at http://prevention.cancer.gov/cp-ctnet).

5. Virtual Biospecimen Inventory System for Clinical Trials

Describe plans for supporting NCI's efforts in management 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. (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 DMACC 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:

• Lead Organizations (LAOs) will be audited on-site annually, and as needed, remotely.
• Participating Organizations (AOs) will be audited remotely on an annual basis, or on site in the following instances:

o the AO has accrued 10 or more participants across all studies in the previous 12 months,

o three years have elapsed since the AO’s last on-site audit.

• For-cause on-site auditing will be conducted on an ad hoc basis.

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

• Development and implementation of the 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: 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 DMACC 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.
• Other operational and administrative support, as needed.

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

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Data Sharing Plan is expected to adhere to the guidelines in the NCI Genomic Data Sharing Policy (https://www.cancer.gov/grants-training/grants-management/nci-policies/genomic-data).
• It is expected that these plans will address data compatibility. Formats, analytical algorithms, computational modeling and visualizations, and other bioinformatics tools resulting from this FOA are expected to be compatible with the NIH-approved bioinformatics platforms, such as those designed and implemented by the NCI Center for Biomedical Informatics and Information Technology (CBIIT) (https://cbiit.cancer.gov/).
• The data sharing plan is also expected to address procedures ensuring that claims of agent efficacy are accurate and reliable (e.g., by establishing an independent response review panel).

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving NIH-defined human subjects research, clinical research, and/or clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions:

Do not complete study records.

Delayed Onset Study

All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions:

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 DMACC will participate as a CP-CTNet clinical trial infrastructure during the implementation of the approved clinical trials.

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

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

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

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

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

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

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 the NIH Grants Policy Statement.

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. 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 Component of the SF424(R&R) Application Package. 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 FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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

For this announcement, note the following:

The overarching goal of the CP-CTNet program is to facilitate the clinical development of novel cancer prevention interventions through the conduct of early phase clinical trials. Achieving this goal will require the CP-CTNet DMACC to operate under outstanding leadership, with robust infrastructure, and a strong record of supporting clinical trials and clinical research activities. Essential for CP-CTNet will be the CP-CTNet DMACC awardees' ability to work as part of a network and effectively collaborate with the CP-CTNet Sites to efficiently and expeditiously conduct early phase clinical trials.

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

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

How well does the proposed DMACC address the needs of the CP-CTNet that it will coordinate? Is the scope of activities proposed for the DMACC appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research proposed through CP-CTnet?

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

Specific for this FOA: How likely is the proposed CP-CTNet DMACC to contribute meaningfully to the CP-CTNet goals by enhancing and streamlining data management, data integration and reporting, and clinical trials auditing in the context of multi-site clinical trials research? Will the proposed strategies, infrastructure, and methods adequately support CP-CTNet’s research goals? Do the approaches and methodologies proposed in the application support and enhance the coordination, conduct and quality of cancer prevention clinical trials?

Are the PD(s)/PI(s) and other personnel well suited to their roles in the DMACC? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing clinical trials? Do the investigators demonstrate significant experience with coordinating collaborative clinical research? If the DMACC is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the DMACC? Does the applicant have experience overseeing selection and management of subawards, if needed?

With regard to the proposed leadership for the DMACC, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Specific for this FOA: How strong is the background of the PD(s)/PI(s) in leading and coordinating collaborative trans-disciplinary clinical trials research? Do the PD(s)/PI(s) demonstrate accomplishments and related experience in multi-institutional clinical trials data management and reporting, clinical trials auditing, accrual support, biospecimen inventory system management, and logistical coordination activities? How well does the organizational structure support the administrative leadership? How well are the other key personnel (e.g., Functional Unit Directors) proposed in the DMACC applicant team suited and qualified to carry out the activities? Do the DMACC key personnel have complementary and integrated expertise and skills? How well will the team be able to contribute unique expertise and perspectives to such joint endeavors?

Does the application propose novel organizational concepts, management strategies, or instrumentation in coordinating clinical trials in CP-CTNet that the DMACC will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts, management strategies or instrumentation proposed?

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

Specific for this FOA: Do the proposed approaches to managing and coordinating DMACC activities include innovative elements, as appropriate, to facilitate efficient and effective operations? How well do the proposed plans for data collection, management, and transmission take advantage of the growing availability of electronic records and interoperability?

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the clinical trials in CP-CTNet that the DMACC will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the CP-CTnet, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? In the early stages of operations of CP-CTNet trials, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the CP-CTNet? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of 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 FOA:

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? 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 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 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? How adequate are plans for participating in the transition of the existing accrual quality improvement and tracking program for the 2012 Consortia (AQuIP)?

How adequate are plans for maintaining and developing a virtual biospecimen inventory system for CP-CTNet in support of NCI's efforts in management and storage of biospecimens from CP-CTNet trials? Do such plans provide for standard clinical and specimen annotations and study-specific information and remote (web-based) real-time access functionality?

How adequate are plans for independent audits of all CP-CTNet Sites as part of the plan for the functional unit focused on Clinical Trials Auditing? Do the proposed plans take into account the frequency of auditing suggested in the FOA? How adequately are plans for on-site and remote auditing, and preparation, distribution and dissemination of reports of audit visit findings and follow-up of visit action items described? How adequately are plans for engagement with CP-CTNet Sites and NCI staff for identifying improvements, increasing efficiency and compliance, ensuring protection of human subjects, and enhancing quality and integrity of CP-CTNet clinical trials described?

How adequately are plans and approaches for providing support for administrative and logistical coordination across CP-CTNet operations described? How adequately are the plans for the development and maintenance of network coordination documents, such as the DMACC Manual of Operations, CP-CTNet standard operating procedures, website content for CP-CTNet, and other procedural documents and materials described? How well are plans for logistical and administrative support for conference calls and meetings 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 CTNet Sites described?

How adequately does the proposed data management and reporting plan address potential challenges related to differences in clinical practice patterns, data management practices, and site-specific approaches to clinical trials management? Does the proposed DMACC 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?

Will the institutional environment in which the DMACC will operate contribute to the probability of success in facilitating the clinical trials conducted in CP-CTNet? Are the institutional support, equipment and other physical resources available to the investigators adequate for the DMACC proposed? Will the DMACC benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

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?

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 DMACC 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)?

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

For research that involves human subjects and meets the criteria for one or more of the six 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.

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 children 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.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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.

Not Applicable

Not Applicable.

Not Applicable.

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

Not Applicable.

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).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

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.

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

As part of the scientific peer review, all applications:

• Will receive a written critique.

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

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 FOA. 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.

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

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

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

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

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

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

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

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee 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).

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that 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 FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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 awardees 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 award 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 awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

• Managing the DMACC’s operations and tasks, including but not limited to data management and reporting, clinical trials auditing, 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.
• Developing and maintaining procedural documents and materials for logistical and administrative support of CP-CTNet.
• Establishing collaborations among the DMACC team, CP-CTNet, and other NCI support organizations.
• Establishing project timelines in coordination with NCI to ensure all required DMACC 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 awardees performance under the award for appropriate collection, review, and distribution of biospecimens collected in association with CP-CTNet trials.

The NCI reserves the right to reduce the budget or withhold an award in the event of substantial awardee underperformance or other substantial failure to comply with the terms of award.

Areas of Joint Responsibility

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 DMACC), 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; and
• Developing agenda and co-organizing with the NCI the annual in-person investigator meeting to be held at NCI (https://prevention.cancer.gov/news-and-events/meetings-and-events/2018-investigators-site)
• 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 LOI solicitations from NCI or as unsolicited LOIs 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 award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the CP-CTNet Group representatives chosen from the CP-CTNet Leadership 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 awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

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

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

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

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten on-time submission, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application processes and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

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

Eva Szabo, MD
National Cancer Institute (NCI)
Telephone: 240-276-7011
Email: szaboe@mail.nih.gov

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: ncirefof@dea.nci.nih.gov

Sean Hine
National Cancer Institute (NCI)
Telephone: 301-276-6291
Email: hines@mail.nih.gov

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.