Statistical issues in randomized trials of cancer screening

Abstract

Background: The evaluation of randomized trials for cancer screening involves special statistical considerations not found in therapeutic trials. Although some of these issues have been discussed previously, we present important recent and new methodologies. Methods: Our emphasis is on simple approaches. Results: We make the following recommendations: (1) Use death from cancer as the primary endpoint, but review death records carefully and report all causes of death (2) Use a simple "causal" estimate to adjust for nonattendance and contamination occurring immediately after randomization (3) Use a simple adaptive estimate to adjust for dilution in follow-up after the last screen Conclusion: The proposed guidelines combine recent methodological work on screening endpoints and noncompliance/contamination with a new adaptive method to adjust for dilution in a study where follow-up continues after the last screen. These guidelines ensure good practice in the design and analysis of randomized trials of cancer screening.