Development of the Microsimulation Model in Cancers of Bladder and Kidney (MiMiC-BlaKy)

Background

The Microsimulation Model in Bladder [BC] and Kidney [KC] cancers has been developed as part of the YORKSURe trial, a feasibility assessment for implementing a targeted study in populations with a high risk of disease-specific mortality in Yorkshire. YORKSURe is a feasibility trial aimed at the early diagnosis of BC through the detection of haematuria in asymptomatic individuals at high risk of mortality from BC1. Following results of the feasibility trial, the aim is to then conduct a large-scale trial, with sufficient power to test any differences in survival. The feasibility trial aims to understand if the proposed approach is robust, appropriate, necessary, and acceptable to participants.

The trial investigates the efficacy of urine dipstick testing for BC detection. A urine dipstick test is a simple diagnostic tool used to screen for abnormalities in the urine. It involves a specially treated strip that is dipped into a urine sample. The strip has reagent pads that change colour upon exposure to various substances such as glucose, protein, blood, and leukocytes, among others. The colour changes on the dipstick are compared to a chart that provides an indication of the presence and approximate concentration of different substances, which can help in the diagnosis of conditions like urinary tract infections, as well as bladder and (much less accurately) kidney cancers. This quick and non-invasive test is routinely used in clinical settings for its speed and convenience in providing immediate results.

To inform the trial design, the mathematical disease model was created with the objective to assess the long-term impact and cost-effectiveness of home dipstick test screening in a population cohort similar to one of the cohorts enrolled in the YORKSURe trial—current and former smokers. The original model focused solely on simulating the natural history of BC. The initial calibration of the BC model revealed that haematuria screening is not cost-effective. However, drawing such a conclusion was deemed premature without factoring in the potential additional benefits of screening, such as the detection of KC. As a result, a combined Bladder and Kidney cancers model, referred to as MiMiC-BlaKy, was subsequently developed.

MiMiC-BlaKy is an individual patient simulation model constructed using the R programming language. Its primary purpose is to facilitate comparisons of the effectiveness, cost-effectiveness, and resource utilisation associated with screening strategies for urological cancers, specifically BC and KC, across diverse population groups. The model simulates the life trajectories of patients and can be tailored to represent various populations, chosen based on predefined criteria.

Each individual within the model possesses a unique set of characteristics that govern their susceptibility to cancer and how they respond to screening and surveillance protocols. Notably, the model spans a lifetime horizon and adopts the perspective of the NHS (National Health Service). In its simulations, MiMiC-BlaKy treats both BC and KC as mutually exclusive events. This means that if an individual develops either BC or KC, they will not experience a primary case of the second disease during their lifetime. This approach is argued by the rarity of such concurrent primary cases and the assumption that patients with history of urological cancers could be followed up for all urological conditions.