Guidance for Cancer Screening Trials

All grant-funded cancer screening protocols awarded after January 2023 are subject to the new Division of Cancer Prevention (DCP) Screening Protocol Requirements and Slow Accrual Stopping Rules. DCP’s goal is to systematically apply these new requirements to ensure that screening protocols contain realistic accrual goals and that potential accrual concerns are addressed before DCP approval of the protocol.

These requirements were developed as part of DCP’s response to the CTAC Cancer Screening Trials Working Group recommendations and were presented to CTAC on November 9, 2022. The CTAC presentation (PDF, 701 KB) and the DCP Implementation Plan (PDF, 307 KB) are available for review. The Implementation Plan contains the DCP Screening Protocol Requirements (Appendix A [PDF, 307 KB]) and preliminary Slow Accrual Stopping Rules (Appendix C [PDF, 307 KB]). The requirements are as follows:

Screening Protocol Requirements

1. Study Design/Study Plan

   1. Eligibility criteria are clearly defined and include populations who experience risk for the condition under study.
   2. The proposed sample size is justified based on site accrual capability, staff experience, and track record with the cohort in similar trials, feasibility studies, endpoints, etc.
   3. The proposed accrual duration is explicitly stated in the protocol document and justified.

2. Recruitment Planning

   1. The protocol contains a comprehensive discussion of the recruitment approach and explicitly details the accrual approaches for racial/ethnic minorities and underrepresented populations.
   2. The recruitment discussion identifies any differential timeline or expected accrual rates for underrepresented populations, citing data for populations that have been shown to enroll later in trial recruitment.
   3. The description addresses any unique structures, relationships, or processes needed to recruit sufficient participants in the proposed timelines.
   4. The protocol confirms that a detailed recruitment plan will be ready for implementation prior to randomizing the first participant.
   5. The process of site selection is described.
   6. The description addresses the inclusion of non-English speakers and how the consent and other patient-facing study materials will be translated into Spanish (at a minimum) and be available before recruitment begins.
   7. DCP requires that large screening trials (>10,000 participants) have a Participant Advisory Board (PAB). A description of the PAB addresses the purpose, function, and responsibilities of the PAB.
   8. The description discusses the process for systematically evaluating and revising the recruitment plan throughout the enrollment period.
   9. A detailed recruitment plan and patient advisory board plan are encouraged and may be included as “Additional Study-Related Documents,” thus allowing document updates independent of a protocol amendment.

3. Accrual Milestones

   1. The protocol contains milestone dates with the expected overall and minority accrual defined for each milestone.

4. Accrual Monitoring

   1. The protocol describes the process for monitoring overall and racial/ethnic minority accrual. The monitoring section of the protocol addresses:
      1. Roles and responsibilities for implementing the monitoring plan.
      2. Frequency and method of monitoring and accrual reporting.
      3. Roles and responsibilities for addressing and reporting accrual that does not meet the milestone.
      4. Communication and coordination between stakeholders for addressing slow accrual.

Preliminary Slow Accrual Stopping Rules

The approach is to evaluate the actual accrual of a trial based upon the protocol’s expected accrual time frame.

• If the actual accrual does not meet the expected accrual at a specified time point, a warning letter will be issued.
• If the accrual improves and meets the next projected period goals, it continues and is monitored closely.
• If the trial accrual does not meet the next projected period goals, then it is terminated for inability to accrue.
  
  Accrual evaluation timepoints (“breakpoints”) are expressed as a percentage of expected accrual at a percentage of the projected accrual time period.
  • First breakpoint: 10% of expected accrual at 25% of projected accrual period
  • Second breakpoint: 25% of expected accrual at 50% of projected accrual period
  • Third breakpoint: 50% of expected accrual at 75% of projected accrual period
  • Fourth breakpoint: 65% of expected accrual at 85% of projected accrual period
  • Fifth breakpoint: 90% of expected accrual at 100% of accrual period