Part 1. Overview Information

Key Dates

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

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

No late applications will be accepted for this Funding Opportunity Announcement.

It is critical that applicants follow the instructions in 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 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 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

This Funding Opportunity Announcement (FOA) is one of three FOAs that will support a comprehensive effort by the National Cancer Institute (NCI) to provide infrastructure to develop the Cancer Screening Research Network (CSRN). The primary goal of the CSRN is the conduct of multi-center cancer screening trials and studies. This Network is designed to take advantage of large and diverse populations receiving routine care in a variety of healthcare settings. The CSRN will engage these populations in rigorous studies focused on cancer screening to improve early cancer detection and evaluate emerging cancer screening modalities with the ultimate goal of reducing cancer incidence, and cancer-related morbidity and mortality.

The CSRN will support the following components that will be individually awarded through the respective FOAs indicated below:

• RFA-CA-23-020: CSRN Accrual, Enrollment, and Screening Sites (ACCESS) Hubs;
• RFA-CA-23-021: CSRN Statistics and Data Management Center (SDMC; this FOA); and
• RFA-CA-23-022: CSRN Coordinating and Communication Center (CCC).

Each key component of the CSRN program is described briefly below:

• CSRN ACCESS Hubs will establish multi-disciplinary teams to recruit participants to CSRN trials and studies, conduct the screening protocols, and participate in the scientific development and implementation of those trials and studies.
• CSRN SDMC will provide statistical expertise and centralized data management, quality control, and reporting in support of CSRN clinical trials and other cancer screening studies.
• CSRN CCC will provide cancer screening expertise and clinical trial leadership and is responsible for the coordination of all aspects of study operations, as well as the development and implementation of communication activities.

Background

Screening for cancer is a process that involves multiple steps and clinical care from primary care or other clinicians. An NCI Cancer Screening Research Network (CSRN) would provide an infrastructure to efficiently conduct cancer screening clinical trials and other important screening-related studies within clinical practice including the recruitment of participants from diverse, frequently underrepresented populations.

The gold standard for the evaluation of a new screening modality is a randomized clinical trial. The CSRN is expected to conduct a variety of randomized control trials and other studies related to cancer screening. Issues in cancer screening are not limited to assessing the benefits and harms of using a technology for cancer screening, but also in the implementation of that technology into the standard-of-care screening. A research network specifically designed to evaluate emerging technologies for cancer screening through randomized controlled trials, and to assess the clinical workflow, integration of these new technologies into standard-of-care screening, and answer other screening-related questions through longitudinal studies is greatly needed.

New emerging technologies, including Multi-Cancer Detection (MCD) assays that evaluate cell-free DNA (cfDNA) or other biological components, are rapidly coming forward for commercial availability without a systematic evaluation for their use in the process of cancer screening. These assays are also referred to as liquid biopsies, cell-free DNA testing, and/or multi-cancer early detection (M.C.E.D) evaluation assays. These assays offer a new way to identify a signal for the detection of multiple different cancers. This technology is potentially useful if it allows early detection of cancer, or if it detects cancers that do not currently have established screening modalities. However, very limited information is known about how to effectively use the different assays for the process of cancer screening. While some information about the analytic performance of MCD assays has been published for several of these tests, there is virtually no information available about the potential benefits (e.g., reduced cancer-specific mortality) or harms (e.g., unnecessary procedures, and over-diagnosis) of cancer screening using these assays.

A variety of challenges exist in the design and conduct of randomized controlled trials which evaluate a single technology to screen for multiple different cancers. As an initial effort, the CSRN will collaboratively develop a feasibility study, referred to as the Vanguard study, to inform the future design of a platform trial to evaluate multiple different technologies for cancer screening in a flexible, but rigorous manner. This will be the major effort for the initial 4 years of the Network. In its preliminary design, the Vanguard study will enroll participants without cancer in one of 3 arms; a control arm, which will receive standard of care cancer screening, and two separate arms each evaluating one MCD test as well as standard of care screening. Due to the nature of the Vanguard study, the NCI will work closely with the Network investigators on protocol design and data analysis. The results of the study are intended to inform a large, definitive, randomized trial which will be implemented by the CSRN.

A comprehensive CSRN would include investigators with expertise in cancer screening and institutions with the capacity to conduct a variety of cancer screening studies, including evaluating the utility of various modalities for screening and surveillance as well as observational studies related to important cancer screening questions. Ideally, the investigators will include a diverse group of medical specialties (e.g., primary care, gastroenterology, gynecology, pulmonology, urology, oncology, radiology, and other relevant specialties), public health experts, and investigators within a range of healthcare delivery systems in the U.S. and across a variety of geographic locations that will enroll populations for cancer screening research studies. Investigators and institutions with experience in disease screening trials and studies are encouraged to participate even if their experience with NCI clinical trials is limited. The CSRN will provide a necessary research infrastructure to support the increasing demand to evaluate the next generation of screening tests and modalities, related health care issues, and implementation strategies.

Key Terms for 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.)
• ACCESS Hub: An organization or group of organizations which consists of institutions that may be individual institutions with affiliate members, healthcare systems, successful practice-based research networks, other relevant institutions, or any combination thereof, that includes a single scientific leadership team that is responsible for study procedures and participant recruitment into CSRN trials and studies.
• Affiliate Organization (AO): An Affiliate Organization refers to a hospital, clinic, primary care practice, or other institution where participants are enrolled on a regular and ongoing basis to CSRN-approved clinical trials.
• 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/).

Overall Goals of CSRN and Scope of this FOA

Overall Goals of CSRN: The overall goal of the CSRN is to evaluate technologies and strategies for the purpose of cancer screening in asymptomatic individuals.

To successfully achieve this goal, the CSRN must:

• Establish the organizational and administrative infrastructure of all necessary components needed to implement cancer screening clinical studies and trials, especially a large screening randomized control trial.
• Develop cancer screening trials to evaluate emerging cancer detection modalities for clinical utility.
• Assess the clinical utility of cancer screening programs or biomarkers of detection including downstream interventions and health outcomes.
• Apply precision medicine approaches to screening using novel risk assessment tools to individualize screening protocols.
• Evaluate the effectiveness, feasibility, and scalability of screening strategies in real-world settings.
• Identify and address technical, process, and/or cultural challenges to adapt the implementation of screening strategies for diverse practice settings.
• Conduct surveillance of cancer screening in populations to track progress and characterize reach and health outcomes across populations.
• Develop cancer screening studies to evaluate clinical workflow and coordination of care.

This Network will conduct clinical trials and other types of research studies to address the clinical utility, effectiveness, implementation, and other questions related to established and emerging screening methods, technologies, and strategies.

Scope of this FOA: The scope of research conducted by the CSRN will include the evaluation of technologies for early detection of cancer, but not for the purpose of detection of recurrence of a previously treated cancer.

To support the CSRN goal, the SDMC will be expected to have the expertise and capacity to contribute the following:

• Provide the statistical leadership and expertise required to assure the effective scientific design and conduct of clinical trials and other cancer screening studies.
• Ensure the integrity of clinical trials including randomization and establishment of interim analyses and early stopping rules for safety and futility.
• Provide high-quality data management support (collection and monitoring) and procedures to ensure appropriate trial and study conduct, reporting of adverse events, and timely trial completion and publication.
• Collect, store, and provide quality control for all participant data for cancer screening trials and studies. This includes, but is not limited to the data management, the design of all trial forms and questionnaires, and the design and operation of systems for secure and timely receipt of trial data from the ACCESS Hubs.
• Support processes to promote the collection of long-term follow-up data for both screen positive and screen negative participants.
• Produce interim trial reports for the Data Safety Monitoring Board.
• Develop and implement a plan for sharing trial data with the research community.
• Collaborate with the NCI program staff including statisticians to develop and execute plans for analysis and quality control of trial data, and assist with trial publications. This will involve data sharing with the NCI statisticians and program staff at pre-specified time points for the Vanguard study.
• Coordinate auditing and trial conduct in a collaborative and integrated manner with the CCC.
• Ensure compliance with all federal and international standards for clinical research.

Requirements:

• Applicants must have prior experience using Medidata Rave for study set-up and data management.
• Applicants must have multi-institutional clinical trial experience.
• Recipients will be required to use the NCI clinical research infrastructure in the conduct of CSRN trials including, but not limited to: The Regulatory Support System (RSS), the Oncology Patient Enrollment Network (OPEN), Registration and Credentialing Repository (RCR), Medidata Rave, Medidata Targeted Source Data Verification (TSDV), the NCI Central Institutional Review Board (CIRB), the CTEP AERS System, Cancer Trial Support Unit (CTSU), and the NCI National Clinical Trials Reporting Program (CTRP). Access the CSRN website at https://prevention.cancer.gov/CSRN for more information about the NCI clinical research infrastructure.
• Recipients will be required to closely collaborate with NIH program staff including statisticians and perform data sharing at pre-defined time points for the Vanguard pilot study.
• Recipients will cooperate with NCI Division of Cancer Prevention (DCP) procedures for accrual monitoring and data entry. Access the CSRN website at https://prevention.cancer.gov/CSRN for more information about DCP procedures for accrual monitoring.

Non-responsive Application

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

• Evaluating technology for the purpose of detecting the recurrence of previously treated cancers.
• Applications that do not address NCI’s scientific mission.

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

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Government

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

Other

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

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 not 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.

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

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

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

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

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

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

Only one application per institution (normally identified by having a unique UEI or NIH IPF number) is allowed

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the 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.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Paul Pinsky, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-7014
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

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.

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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.

Facilities & Other Resources:

In addition to the standard items for this attachment, provide documentation of SDMC facilities and equipment (including computer hardware and software) as well as the information technology (IT) support for central storage, security, analysis, and retrieval of clinical data for the SDMC that will be utilized in CSRN trials.

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 Statistics and Data Management Clinical Trials and Studies (Use filename: Stats Data Management.pdf ): List all multi-center, completed clinical trials and studies for which the applicant team has led and coordinated the statistics and data management 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 open, and additional columns for significant and relevant project outcomes and publications.

Attachment 2: General Data Quality and Timeliness Table (Use filename: Data and Timeliness.pdf): Provide a table detailing general data timeliness and quality for the trials listed in attachment 1. The column headings for the table should include Trial Name, Reporting Year, % Eligible Patients, Eligibility Case Report Form (CRF) Reporting % Timeliness, Eligibility CRF Reporting % Accuracy, Off-Study CRF Reporting % Timeliness, and Off-Study CRF Reporting % Accuracy. The applicant team can select other major CRF categories that it believes represent the best measures of the timeliness of general data submission.

Attachment 3: Key Statistical Standard Operating Procedures (Use filename: Stats Key SOP.pdf): Provide key procedures for statistical trial design and analysis (e.g., guidelines for interim monitoring, general procedures for sample size estimation, accrual rate estimation, and choice of testing and estimation procedures).

Attachment 4: Key Data Management Procedures (Use filename: DM Key SOP.pdf): Provide key procedures for data management.

Attachment 5: Conflict of Interest Policy (Use filename: COI.pdf): Provide documentation of the Conflict of Interest Policy used by the SDMC to ensure that staff working on the design, monitoring, and analysis of specific trials do not have any conflicts of interest with respect to the trials. In this attachment, the SDMC should also describe the policies it has in place to ensure that outcome data is guarded/blinded from other investigators on the study team (e.g., clinical investigators/study PIs) prior to the study's final analysis to avoid investigator bias in oversight/conduct of the trial.

Attachment 6: Key Procedures to Ensure Security and Confidentiality of Patient Data (Use filename: Data Security.pdf): Provide documentation of key procedures for ensuring the security and confidentiality of patient data, including protected health information.

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

R&R Budget

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

Important Note on Budget: The requested budget for the SDMC should not include costs for standardized central operational, regulatory, and administrative support provided by the NCI or existing NCI Contractors or the tasks/activities to be performed by the CCC or ACCESS Hubs.

Personnel Effort

• A minimum effort level of 1.8 person-months is required for the designated PD/PI for a single PI project. In the 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.

Trial Costs

• 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. (Note: The license and specifications for the CDMS will be provided by the NCI).
• Independent consulting with Medidata Rave for additional support.
• 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 specialized statistical hardware and software.

Travel funds

• Annual meeting to be held in person. Please include travel costs for PI’s and administrative personnel.

Notes:

• Available funds may increase after year 1, dependent upon accrual to the Vanguard study.
• The following costs should not be included in the budget:
  • Costs for alterations and renovations.
  • Costs for supporting activities that will be provided by the CCC, ACCESS Hubs or covered by services/functions funded directly by NCI outside of this FOA such as the NCI research clinical infrastructure.

R&R Subaward Budget

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 Aims

Describe the objectives of the SDMC in terms of providing robust statistical design and analysis plans for clinical trials and trial monitoring, as well as appropriate data management (collection and monitoring) processes and procedures for clinical trials, including the impact of these plans on ensuring appropriate trial conduct, timely trial completion, and data validity.

Research Strategy

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

Sub-section A. SDMC Organizational Structure and Statistical Leadership in Clinical Trials:

• Describe the organizational structure of the SDMC.
• Describe the leadership of the SDMC and the qualifications of key personnel who would be responsible for assisting with the study design, data collection, monitoring, and data analysis for CSRN trials and other studies.
• Describe how the SDMC will handle collaboration with the CCC and ACCESS Hub investigators and subcommittees in protocol development, monitoring, analysis planning, and publication drafting.

Sub-section B. SDMC Approach for the CSRN and Statistical Experience with Multi-Center Clinical Trials:

• Describe the statistical approach to trial design and analysis plans for multi-institutional clinical trials, including guidelines for interim monitoring and general procedures for sample size estimation and randomization for potential CSRN screening trials and studies.
• Provide an example (or several) of a previous trial(s) or study(ies) where the applicant designed and executed participant randomization, early stopping rules for safety and futility, and performed interim analyses including participant demographic analyses.
• Describe how the SDMC will ensure that final study analyses are performed in a manner to provide timely publication of study results and results reporting per NIH/NCI and federal regulations.
• Describe the establishment and management of the Data Safety and Monitoring Board (DSMB) and the type of reports that will be generated.
• Provide an example(s) of how the SDMC has provided clinical data in a timely and user-friendly format for public access to data from completed clinical trials and how this approach will be applied to CSRN studies.
• Describe the flow and review of data following submission from individual ACCESS Hubs and the CCC including data quality assurance.
• Describe the procedures for the safe storage of study data.
• Describe efforts to use electronic infrastructure to more efficiently collect patient-level data from ACCESS Hubs.
• Describe procedures for study monitoring as well for data quality control and accuracy verification.
• Describe how data collection tools including questionnaires will be developed.
• Describe prior experience building databases using Medidata Rave for multi-center clinical trials.

Sub-section C. SDMC Approach to the Large Clinical Trial Using the Vanguard (pilot) study:

The initial role of the CSRN will be to perform a pilot study called the Vanguard study that assesses the feasibility of initiating a randomized control trial (RTC) of multi-cancer detection (MCD) assays. This study would inform the design of a future RTC to assess the clinical utility of MCD assays for cancer screening. After reading the following design of the Vanguard study, describe the statistical and data management approach to a large clinical trial that would build upon the Vanguard study.

Objectives of the Vanguard study:

1. Assess participant willingness to be randomized to cancer screening with MCD assays versus a control arm.
2. Determine the extent to which participants will adhere to MCD testing and diagnostic follow-up.
3. Evaluate the feasibility of the protocol-defined diagnostic workflow for the detection of various cancer types.
4. Determine the reliability and timeliness with which participating MCD companies can process the de-identified blood specimens for testing and return results.
5. Identify facilitators and barriers to the recruitment and retention of diverse groups of participants and assess the extent to which underserved populations of participants can be recruited into an RCT to evaluate MCD assays for clinical utility.

Preliminary Design of the Vanguard Study

The Vanguard study will randomize participants to one of 3 arms. Each arm will contain approximately 8000 individuals. Arm 1 will be the control arm and participants allocated to arm 1 will receive standard of care screening. Arms 2 and 3 will each receive a different MCD test annually for 2 years in addition to standard of care screening. Participants in MCD arms will undergo additional diagnostic tests based on a positive MCD result and the type of cancer that the MCD is intended to test for and/or identifies (for example if an MCD indicates the participant has a GI malignancy, they will undergo a GI malignancy workup). It is anticipated that 1% of assay results will be positive and approximately 60% of positive results will reach a diagnostic resolution.

Describe the approach to a large clinical trial from a statistical and data management perspective that would build on the results of the described Vanguard study.

Letters of Support

Provide a general Institutional Letter of Support (i.e., Letter of Support from the primary applicant institution or organization supporting the SDMC application).

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

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

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the 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.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

Applications must add and complete the Delayed Onset Study record and must check the box "Anticipated Clinical Trial?"

Study Title--use: "Multiple Delayed Onset Studies"

Justification Attachment: Indicate that the clinical trials will be designed and conducted by the CSRN 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 CSRN.

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

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

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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

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

Pre-award costs are allowable only as described in 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 How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

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

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

Section V. Application Review Information

1. Criteria

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

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) will not be evaluated at time of review.

For this particular announcement, note the following:

The overarching goal of the Cancer Screening Research Network (CSRN) is to establish the infrastructure to develop and conduct cancer screening clinical trials and studies. The Statistics and Data Management Center (SDMC) will provide statistical design, data management, and data analysis capacity to the Network to support cancer screening trials. Achieving this goal will require the SDMC to operate under outstanding leadership, with robust infrastructure, and a strong record of supporting clinical trials and clinical research activities. Essential for CSRN function will be the SDMC's ability to work as part of a network and effectively collaborate with the CCC and ACCESS Hubs to efficiently and comprehensively conduct cancer screening trials and studies. Randomized controlled trials, by their nature may not be innovative, but may be essential to advance a field. Thus, innovation may be de-emphasized and a history of excellence in performance of clinical trials should be prioritized.

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.

Overall Impact

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

Scored Review Criteria

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

Significance

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

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 well does the proposed SDMC address the needs for statistical design, analysis and data management for cancer screening clinical trials and studies? Is the scope of activities proposed for the SDMC appropriate to meet the needs of the CSRN? Will successful completion of the aims bring unique advantages or capabilities to the research proposed through CSRN?

Investigator(s)

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

With regard to the proposed leadership for the project, 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 qualified are the statisticians and data managers to lead the statistics and data management components of large, multi-institutional studies? How much experience do the SDMC investigators have in successful collaborations for multi-institutional projects and the successful completion of multi-institutional trials of the scale proposed by the CSRN?

Innovation

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

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

How comprehensive is the ability of the statistical team to conduct rigorous statistical analysis and successfully publish their findings? How well has the team utilized information regarding the design of the Vanguard pilot to inform the design of a larger definitive trial? Do the proposed approaches to managing and coordinating data management activities include innovative elements, as appropriate? How well do the proposed plans for data collection, management, and transmission take advantage of the growing availability of electronic data capture and interoperability?

Approach

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

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 are the plans for coordination with the CCC and ACCESS Hub investigators to accomplish the objectives of the CSRN and participate in the collective management of the CSRN? Given the SDMC's prior experience, how likely is it to collect high quality data, and establish adequate monitoring procedures sufficient for CSRN studies? How experienced is the applicant in performing statistics and data analysis at the scale of the CSRN? How adequate were the described procedures for randomization, blinding, interim analyses, and early stopping rules for safety and futility? How comprehensive is the methodology described for data collection tools? How comprehensive is the applicant’s plan for compliance with NIH and Federal regulations? How adequate is the proposed plan for data management reporting in support of multi-institutional research and collaboration within the CSRN? How adequate is the description of the flow and review of data, and data quality assurance? 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 CSRN? How adequate are described procedures for study monitoring as well for data quality control and accuracy verification? How feasible and comprehensive is the proposed approach to the multi institutional clinical trial?

Environment

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

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

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

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

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

Specific for this FOA

Does the applicant have a well-defined organizational structure and clearly defined roles and responsibilities for its staff? What is the probability of success of facilitating the clinical trials conducted in the CSRN? Are the institutional support systems, equipment, and other physical resources available to the investigators adequate for the SDMC proposed? How will the SDMC benefit from unique features of the institutional environment, infrastructure, or personnel? How well do the data management systems employed by the applicant integrate with required results reporting systems? How adequate is the plan for data security?

Additional Review Criteria

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

Study Timeline

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

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

Protections for Human Subjects

For research that involves human subjects but does not involve one of the 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 categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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.

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

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.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) will not be evaluated at time of review.

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

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

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

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

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

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

Applications will be assigned 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 National Cancer Advisory 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.
• Geographic diversity and distribution of healthcare entities.
• Relevance of the proposed project to program priorities.
• Demonstration of successful data sharing of completed trials or studies.

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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 recipient's business official.

Recipients 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 and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

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

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

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

2. Administrative and National Policy Requirements

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, Recipients, and Activities, including of note, but not limited to:

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

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

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identity, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

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.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.
• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

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 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH's 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

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

• Developing an overall strategy to provide statistical expertise for effective scientific design and conduct of clinical trials and other studies led by the CSRN.
• Managing the SDMC’s operations and tasks, including but not limited to data management and reporting for the CSRN.
• Compliance with the use of Medidata RAVE for the centralized clinical trial data management system to support CSRN trials including coordinating and leveraging, where feasible, NCI’s Common Data Elements.
• Ensuring use of the NCI CIRB for all CSRN multi-site clinical trials and eligible related studies.
• Compliance with Network operating policies developed by the Steering Committee.
• Compliance with NCI policies for registration of clinical trials in clinicaltrials.gov and NCI's Clinical Trials Reporting Program (CTRP), publication, and trial data deposit to NCI Cancer Data Access System.
• Protecting the confidentiality of CSRN clinical trial data and the information shared with CSRN organizations, including, without limitation, unpublished data, protocols, data analysis, and other confidential information received by CSRN personnel.
• Providing routine and ad-hoc reports and data to the CSRN and NCI.
• Collaborating with the CCC to maintain a clinical trials accrual quality improvement program and accrual tracking system.
• Collaborating with the CCC to maintain a biospecimen inventory system to support tracking the collection and use of the biospecimens and related data.
• Collaborating with NCI scientists (statisticians) and program staff and data sharing with NCI at pre-specified time points.
• Ensuring development of and compliance with federal regulations including the development of complaint standard operating procedures covering all aspects of clinical trial design, trial conduct (including compliance with Good Clinical Practice (GCP), manual of operation, data management, study monitoring, and data analysis.
• Development of and compliance with data safety/monitoring plans and Data Safety Monitoring Board policy for applicable trials, and training for Clinical Research Associates (CRAs) at member participating sites and Study Chairs/Teams about their responsibilities for study monitoring and data management.
• Use of the NCI clinical trial network infrastructure for all CSRN trials and studies.
• Participating in the collective management of the Network including shared policies and procedures, as well as participation in appropriate CSRN Program activities and initiatives (e.g., NCI Scientific Steering Committees, NCI central IRBs).
• 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).
• Compliance with CSRN/NCI/NIH timelines and policies for publication, and trial- data deposit in the NCI Cancer Data Access System (CDAS).
• Compliance with DCP process for accrual monitoring.
• Participation in the Vanguard study.
• Supplying additional progress-related information, in addition to the standard annual Research Performance Progress Report (RPPR) submission as needed.
• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, NIH, and NCI policies and within the limits of any accepted binding NCI/NIH collaborative agreements with biotechnology and as governed by NCI-approved Data Sharing Plans and NCI-approved review for use of biospecimens collected in association with CSRN trials.

NCI program staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. The substantially involved NCI program staff member(s), acting as Project Scientist(s), will coordinate in a centralized fashion various activities of the recipient. Specific responsibilities of the NCI Project Scientist(s) will include, but will not be limited to:

• Ensuring that plans for statistical design and analysis, data management, and data reporting of clinical trials proposed are within the research scope of the CSRN and relevant to the state-of-the-science, NIH/NCI priorities, resources, and availability of funding.
• Collaboratively working with CSRN recipients to manage scientific, administrative, and implementation issues associated with their participation in the conduct of clinical trials across the CSRN.
• Informing the CSRN recipient PD(s)/PI(s) of scientific opportunities resulting from NCI-supported clinical research programs and facilitating collaborations between the CSRN 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.
• Facilitating coordination of the clinical trial activities and collaborations between the Network and other NCI-sponsored programs and investigators.
• Serving as scientific liaisons to the SDMC.
• Providing oversight for data and safety monitoring plans and boards for CSRN clinical trials.
• Providing oversight for data management and monitoring programs for CSRN trials, as well as audits and quality assurance site visits (on-site and remote), and reviewing audit reports.
• Facilitating the evaluation of clinical trial concepts and protocol development as well as review and approval of final trial protocols, including statistical analysis plans.
• Ensuring compliance with FDA requirements for investigational devices and ensuring compliance with OHRP, NIH, and other federal requirements and regulations for research involving human research subjects.
• Assuming responsibilities as a sponsor for device development for NCI-sponsored or co-sponsored Investigational Device Exemption (IDE) clinical trials.
• Advising recipients concerning mechanisms established by the recipients for quality control of diagnostic modalities.
• Monitoring the progress and performance of the SDMC.
• The NCI will have access to all raw data (including imaging data) from clinical trial participants collected and/or generated under this Cooperative Agreement and may periodically review the data. The NCI may also review all records related to recipients performance under the award for appropriate collection, review, and distribution of biospecimens collected in association with CSRN trials and studies.
• Collaborating on data analyses using data from CSRN studies, and being co-authors on publications.
• The NCI reserves the right to reduce the budget or withhold an award in the event of substantial recipient underperformance or other substantial failures to comply with the terms of the award.

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

Areas of Joint Responsibility include:

Steering Committee: A Steering Committee will serve as the main governing body of the CSRN that will integrate the efforts of all CSRN recipients and provide oversight of collaborative activities.

The Steering Committee will consist of the following voting members:

• Two representatives, one of whom must be the PD/PI, from each ACCESS Hub will collectively have one vote;
• Two representatives, one of whom must be the PD/PI, from the CCC will collectively have one vote;
• Two representatives, one of whom must be the PD/PI, from the SDMC will collectively have one vote; and
• NCI Project Scientist(s), who will collectively have one vote for NCI.

Additional NCI Program Officials may join the Steering Committee as non-voting members.

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

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

Key responsibilities of the Steering Committee include:

• Holding meetings at regular intervals;
• Developing Network operating policies for implementation by the CSRN recipients;
• Approving the Manual of Operations for the CSRN;
• Facilitating the process of joint development of appropriate screening trial protocols by CSRN components and NCI (see below);
• Other programmatic responsibilities to be addressed jointly, as needed, by the CSRN award recipients and the NCI staff; and
• Establishing sub-committees for cross-Network collaborative activities.

Subcommittees/Working groups. The Steering Committee may establish subcommittees or working groups for specific purposes (e.g., recruitment and retention, policies and procedures, development of new concepts or protocols, etc) to facilitate the function of the Network. 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 Screening Trial/Study Protocols by CSRN recipients and NCI. CSRN award recipients will be expected to participate as active team members in protocol development. The NCI will support award recipients with the development of appropriate protocols. The first anticipated protocol will be for the Vanguard study. 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 CSRN, as appropriate;
• Development of concepts for new clinical trials, either in response to solicitations from NCI or as unsolicited letters of intent; and
• Meeting as frequently as needed to assure optimal study performance and to review studies performed under the CSRN awards.

Dispute Resolution:

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

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

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

The Vanguard study will be funded in part by the Beau Biden Cancer Moonshot Initiative. As a result, for the Vanguard study, the following data sharing policies and biobanking principles apply:

Cancer Moonshot Open Access and Data Sharing Policy:Utilizing the provision outlined in the 21st Century Cures Act, NCI has established a data sharing policy for projects that are funded as part of the Beau Biden Cancer Moonshot Initiative that requires applicants to submit a Public Access and Data Sharing Plan that: (1) describes their proposed process for making resulting publications and to the extent possible, the underlying primary data immediately and broadly available to the public upon publication; and (2) if applicable, provides a justification to NCI if such sharing is not possible. NCI will give competitive preference and funding priority to applications that comply with the above policy. The data sharing plan will become a term and condition of award.

Guiding Principles for Cancer Moonshot Biobanking Activities:The goal in developing these guiding principles is to accelerate research by a) increasing the availability of biospecimens for Cancer Moonshot-related and other biomedical research through facilitation of investigator to investigator sharing of biospecimens, and b) increasing the reproducibility of Cancer Moonshot research through improved biospecimen practices and corresponding annotation. These guiding principles also seek to facilitate, where possible, increased engagement of research participants through researchers' communication of aggregate research results and, in some cases, individual genomic findings that may be medically actionable for research participants. NCI will give competitive preference and funding priority to applications that conform to the "Guiding Principles for Cancer Moonshot Biobanking Activities" (http://biospecimens.cancer.gov/programs/cancermoonshot/principles) and are consistent with the "2016 NCI Best Practices for Biospecimen Resources" (https://biospecimens.cancer.gov/bestpractices/).

4. Reporting

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

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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 and 2 CFR Part 200 Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

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

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

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

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

Paul Pinsky, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-7014
Email: [email protected]

Elyse LeeVan, M.D.
National Cancer Institute (NCI)
Telephone: 240-276-7314
Email: [email protected]

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

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

Section VIII. Other Information

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.