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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 cu