When gold standards are not so golden: prevalence bias in randomized trials on endoscopic colorectal cancer screening

Randomized trials on the effectiveness of screening endoscopy in reducing colorectal cancer (CRC) risk have reported statistically significant, but rather modest reduction of CRC risk by the screening offer. However, risk estimates in these trials included substantial proportions of prevalent CRC cases which were early detected, but could not possibly have been prevented by screening. Thereby, a key principle of randomized prevention trials is violated that only "at risk" persons who do not yet have the disease one aims to prevent should be included in measures of preventive effects. Using recently published data from the Nordic-European Initiative on Colorectal Cancer (NordICC) trial as an example, we illustrate that approaches aimed to account for "prevalence bias" lead to effect estimates that are substantially larger than those reported in the trial and more in line with results from observational studies and real life settings. More rigorous methodological work is needed to develop effective and user-friendly tools to prevent or adjust for prevalence bias in future screening studies.