Effects of screening for colorectal cancer: Development, documentation and validation of a multistate Markov model

Simulation models are a powerful tool to overcome gaps of evidence needed to inform medical decision-making. Here, we present development and application of COSIMO, a Markov-based Colorectal Cancer (CRC) Multi-state Simulation Model to simulate effects of CRC screening, along with a thorough assessment of the model's ability to reproduce real-life outcomes. Firstly, we provide a comprehensive documentation of COSIMO's development, structure and assumptions. Secondly, to assess the model's external validity, we compared model-derived cumulative incidence and prevalences of colorectal neoplasms to (a) results from KolosSal, a study in German screening colonoscopy participants, (b) registry-based estimates of CRC incidence in Germany, and (c) outcome patterns of randomized sigmoidoscopy screening studies. We found that (a) more than 90% of observed prevalences in the KolosSal study were within the 95% confidence intervals of the model-predicted neoplasm prevalences; (b) the 15-year cumulative CRC incidences estimated by simulations for the German population deviated by 0.0% to 0.2% units in men and 0.0% to 0.3% units in women when compared to corresponding registry-derived estimates; and (c) the time course of cumulative CRC incidence and mortality in the modeled intervention group and control group closely resembles the time course reported from sigmoidoscopy screening trials. Overall, COSIMO adequately predicted colorectal neoplasm prevalences and incidences in a German population for up to 25 years, with estimated patterns of the effect of screening colonoscopy resembling those seen in registry data and real-world studies. This suggests that the model may represent a valid tool to assess the comparative effectiveness of CRC screening strategies.