A PROGRESSIVE CALIBRATION PROCEDURE FOR INDIVIDUALIZED COLORECTAL CANCER SCREENING STUDY

Purpose: Current guidelines on colorectal cancer (CRC) screening do not consider gender nor do they differ by age. Recent evidence, though, has shown that polyps form earlier and progress faster in men than women. Economic models for tailoring the guidelines need efficient and accurate quantification of model parameters, especially those governing the incidence and growth of adenomas for different age-gender groups. However, this model calibration is challenging given the large numbers of model parameters and outcomes. The purpose of our study is to generate insights into calibration of discrete-event simulations for CRC screening cost-effectiveness analyses.

Methods: We developed a progressive fitting procedure to calibrate a discrete-event simulation model, which extended the 2007 Vanderbilt-NCSU CRC (VNCS) model by replacing each probability distribution governing adenoma state dwelling with a set of age-gender-specific distributions and synthesizing the probability distribution parameters into three growth rate parameters (incidence of non-advanced adenoma; progression to advanced-adenoma; and progression to CRC) for each age-gender group. Note that when VNCS was built, there were no age-gender-specific data on transitions from non-advanced to advanced adenoma.

To estimate the growth rate parameters, the developed procedure started with younger populations. It ran the simulation with smaller sample size and fewer replications for computational efficiency and progressively increased the size and replications to ensure statistical significance of the fitted results. In the calibration, we compared the average simulated non-advanced and advanced adenoma incidences with recent evidence from a 7-year observational study published recently. For each set of parameters pertaining to a gender and a 5-year age group, we created 35 hypothetical cohorts, each of which corresponds to particular birth and screening years.

Results: Our calibration procedure produced results comparable to recent evidence. We captured the features in the simulation that a male cohort had higher risks of developing both non-advanced and advanced adenomas than a female cohort of the same age; the risks for both genders were significantly different between age groups.

Conclusions: We proposed an efficient and accurate calibration procedure for economic studies of CRC screening strategy tailoring. The procedure took into account the disease natural history and exploited recent developments in model-based parameter estimation. We demonstrated its performance by updating the VNCS model. More broadly, the developed procedure can be applied to other simulation-based economic studies on individualized medicine.