Pre-application Webinar RFA-CA-23-021- - PowerPoint Presentation

1. Pre-application WebinarRFA-CA-23-021- Statistics and Data Management CenterLori Minasian, MD, Deputy DirectorDivision of Cancer PreventionDecember 16, 2022Cancer Screening Research Network(CSRN)

2. RFAs released on November 18, 2022

3. Purpose and RationaleThe purpose of the CSRN is to address questions related to the cancer screening continuum of care:Efficacy, effectiveness, best practices, adoption, adaption, implementation, etc. for each step in this continuum

4. Overall Goals of CSRN Establish the organizational infrastructure for all necessary components to implement cancer screening clinical trials and studiesDevelop cancer screening trials/studies to evaluate emerging technologiesAssess the clinical utility of cancer screening programs or biomarkers of detection including downstream interventions and health outcomesApply precision medicine approaches to screening using novel risk assessment tools to individualize screening protocolsEvaluate the effectiveness, feasibility, and scalability of screening strategiesIdentify and address technical, process, and cultural challenges to adapt implementation of screening strategiesConduct surveillance of cancer screening in diverse populationsDevelop cancer screening studies to evaluate clinical workflow

5. CSRN Structure

6. Goals of the Statistics and Data Management CenterProvide 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.

7. Goals of the Statistics and Data Management Center 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.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.

8. CSRN Will Use the NCI Clinical Research Infrastructurehttps://prevention.cancer.gov/CSRN

9. Important Information about the Application The Research Strategy is limited to 12 pages

10. AttachmentsAttachment 1: Completed Statistics and Data Management Clinical Trials and Studies. 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. Attachment 2: General Data Quality and Timeliness Table. Provide a table detailing general data timeliness and quality for the trials listed in attachment 1. Attachment 3: Key Statistical Standard Operating Procedures. 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. Provide key procedures for data management.Attachment 5: Conflict of Interest Policy. 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. Attachment 6: Key Procedures to Ensure Security and Confidentiality of Patient Data. Provide documentation of key procedures for ensuring the security and confidentiality of patient data, including protected health information.

11. Research Plan

12. Research Plan: Organizational Structure & Collaboration 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.Describe how data collection tools including questionnaires will be developed.

13. Research Plan: Clinical Trials Development and SupportDescribe 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 examples of previous studies 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.Describe procedures for study monitoring as well for data quality control and accuracy verification.

14. Research Plan: Data Management 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 prior experience building databases using Medidata Rave for multi-center clinical trials.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.

15. Pilot or Feasibility Study The Vanguard StudyThe Vanguard study is a preliminary designThe protocol will require input from each CSRN component

16. The Vanguard StudyPilot and feasibility study Basic parameters of the Vanguard are described in each CSRN RFA (Research Plan, Section IV)

17. Preliminary Design for the Vanguard StudyThe 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

18. SDMC and the Vanguard StudyDescribe 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.May identify specific assumptions that you would make in describing the approach.

19. Questions?

20. Thank you!Please access https://prevention.cancer.gov/CSRN for up to date information and FAQs for the CSRN

21. NCI OUT Slate