Variability in Adenoma Detection Rate in Control Groups of Randomized Colonoscopy Trials

Background and aims: Adenoma Detection Rate (ADR) is still the main surrogate outcome parameter of screening colonoscopy, but most of the studies included mixed indications and basic ADR is quite variable. We therefore looked at the control groups in randomized ADR trials using advanced imaging or mechanical methods to find out whether indications or other factors influence ADR levels. Methods: Patients in the control groups of randomized controlled trials (RCTs) on ADR increase using various methods were collected based on a systematic review; this control group had to use high-definition (HD) white-light endoscopy performed between 2008 and 2021. Random-effects meta-analysis was used to pool ADR in control groups and its 95% confidence interval (CI) according to the following parameters: clinical (indication and demographic), study setting (tandem/parallel, N° centers, sample size), and technical (type of intervention, withdrawal time). Inter-study heterogeneity was reported with I-squared statistic. Multivariable mixed-effects meta-regression was performed for potentially relevant variables. Results: 25,304 patients from 80 studies in the respective control groups were included. ADR in control arms varied between 8.2% and 68.1% with a high degree of heterogeneity (I2 = 95.1%; random-effect pooled value: 37.5% [34.6‒40.5]). There was no difference in ADR levels between primary colonoscopy screening (12 RCTs, 15%), and mixed indications including screening/surveillance and diagnostic colonoscopy; however, FIT as an indication for colonoscopy was an independent predictor of ADR (OR: 1.6 [1.1‒2.4]). Other well-known parameters were confirmed by our analysis such as age (OR: 1.038 [1.004‒1.074]) and sex (male sex: OR: 1.02 [1.01‒1.03) as well withdrawal time (OR: 1.1 [1.0‒1.1). The type of intervention (imaging vs. mechanical) had no influence, but methodological factors did: more recent year of publication and smaller sample size were associated with higher ADR. Conclusions: A high level of variability was found in the level of ADR in the controls of RCTs. With regards to indications, only FIT-based colonoscopy studies influenced basic ADR, primary colonoscopy screening appeared to be similar to other indications. Standardization for variables related to clinical, methodological, and technical parameters is required to achieve generalizability and reproducibility.