Estimation of overdiagnosis in breast cancer screening using a non-homogeneous multi-state model: A simulation study.

Objectives Overdiagnosis is regarded as a harm of screening. We aimed to develop a non-homogeneous multi-state model to consider the age-specific transition rates for estimation of overdiagnosis, to validate the model by a simulation study where the true frequency of overdiagnosis can be calculated, and to compare our estimate with the cumulative incidence method. Methods We constructed a four-state model to describe the natural history of breast cancer. The latent disease progression and the observed states for each individual were simulated in a trial with biennial screening of women aged 51-69 and a control group of the same size without screening. We performed 100 repetitions of the simulation with one million women to evaluate the performance of estimates. A sensitivity analysis with reduced number of controls was performed to imitate the data from the service screening programme. Results Based on the 100 repetitions, the mean value of the true frequency of overdiagnosis was 12.5% and the average estimates by the cumulative incidence method and the multi-state model were 12.9% (interquartile range: 2.46%) and 13.4% (interquartile range: 2.16%), respectively. The multi-state model had a greater bias of overdiagnosis than the cumulative incidence method, but the variation in the estimates was smaller. When the number of unscreened group was reduced, the variation of multi-state model estimates increased. Conclusions The multi-state model produces a proper estimate of overdiagnosis and the results are comparable with the cumulative incidence method. The multi-state model can be used in the estimation of overdiagnosis, and might be useful for the ongoing service screening programmes.