Brenner Hermann, Holland-Letz Tim, Hoffmeister Michael, Heisser Thomas
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
J Clin Epidemiol. 2025 Apr;180:111669. doi: 10.1016/j.jclinepi.2025.111669. Epub 2025 Jan 10.
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.
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.
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.
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.
最近，北欧-欧洲结直肠癌倡议（NordICC）试验这一随机对照试验首次报告了提供筛查结肠镜检查降低结直肠癌（CRC）发病率和死亡率的结果。尽管进行了随机分组，但在受邀组中，因癌症登记记录的诊断日期早于招募日期而在随机分组后排除CRC病例的比例，比常规护理组低得多。我们旨在评估这种差异排除对试验中CRC风险效应估计值的影响。
我们比较了因癌症登记记录的诊断日期而报告的随机分组后CRC病例排除情况，并针对受邀组和常规护理组中报告的随机分组后CRC病例差异排除情况，得出了调整后的CRC风险效应估计值。
在一项包括NordICC研究所有四个国家参与者的分析中，报告的随机分组后CRC病例排除比例在受邀组和常规护理组中分别最初报告为52/31472（0.17%）和159/63133（0.25%）（P <.005），而在对其中三个国家10年随访数据的最新分析中为52/28277（0.20%）和164/56529（0.29%）（P = 0.018）。在意向性筛查分析中，考虑差异排除比例后，估计的CRC风险降低率（95%CI）从最初报告的18%（7%-30%）增加到25%（95%CI 13%-35%）。在调整后的符合方案分析中，筛查参与者中估计的CRC风险降低率从最初报告的31%（17%-45%）增加到50%（25%-69%）。
在迄今为止唯一一项关于筛查结肠镜检查长期效果的随机对照试验中，考虑CRC病例随机分组后的差异排除会导致比报告更强的效应估计值。
