Screening Trials

The most rigorous approach to evaluating screening interventions for the early detection of disease is the randomized controlled trial (RCT). RCTs are major undertakings requiring substantial resources to enroll and follow large populations over long time periods. Consequently, it is important that such trials be carefully conducted to ensure high quality information and scientifically valid results. The purpose of this chapter is to discuss some of the intricacies of screening trial design, analysis, and monitoring. General design considerations include the choice of interval between screens, the number of screening rounds, and duration of follow-up. A crucial issue in screening trials is choice of the proper outcome measure. This should reflect the impact of the intervention on the clinical outcome for the disease of interest. In cancer screening, the most valid endpoint is the trial population cause-specific mortality. Concerns about lead time bias, length bias and overdiagnosis bias that render other endpoints questionable are discussed. Following presentation of an approach to sample-size calculation for these trials, there is a discussion of commonly employed data analysis methods, including comparison of cause-specific mortality rates between screened and control arms as the primary analysis. Lastly there is a discussion of topics to address in monitoring an evolving screening trial. Examples from completed or ongoing cancer screening trials are used throughout the presentation.