Accounting for differential exclusions in the Nordic-European initiative on colorectal cancer trial discloses stronger-than-reported effects of screening colonoscopy

Objectives

Recently, results on colorectal cancer (CRC) incidence and mortality reduction by the offer of screening colonoscopy were reported for the first time from a randomized controlled trial (RCT), the Nordic-European Initiative on Colorectal Cancer (NordICC) trial. Despite randomization, there was a substantially lower proportion of postrandomization exclusions of CRC cases due to cancer registry-recorded date of diagnosis before recruitment in the invited group than in the usual-care group. We aimed to evaluate the impact of such differential exclusions on the trial's effect estimates on CRC risk.

Study Design and Setting

We compared reported postrandomization exclusions of CRC cases due to cancer registry-recorded date of diagnosis, and we derived adjusted effect estimates on CRC risk accounting for the reported differential postrandomization exclusion of CRC cases in the invited group and the usual-care group.

Results

Reported postrandomization exclusion proportions of CRC cases were originally reported as 52/31,472 (0.17%) and 159/63,133 (0.25%) in the invited and usual-care group, respectively, (P < .005) in an analysis, including participants from all four NordICCstudy countries and as 52/28,277 (0.20%) and 164/56,529 (0.29%) in the recent analysis of 10-year follow-up data from three of the countries (P = .018). Accounting for the differential exclusion proportions increased the estimated CRC risk reduction (95% CI) from originally reported 18% (7%–30%) to 25% (95% CI 13%–35%) in intention-to-screen analysis. Estimated reduction of CRC risk among screening attenders increased from originally reported 31% (17%–45%) to 50% (25%–69%) in adjusted per-protocol analysis.

Conclusion

Accounting for differential postrandomization exclusions of CRC cases leads to stronger-than-reported effect estimates in the so far only RCT on long-term effects of screening colonoscopy.