Abstract
Objective This study constructs, calibrates, and verifies a mathematical simulation model designed to project the natural history of ESCC and is intended to serve as a platform for testing the benefits and cost-effectiveness of primary and secondary ESCC prevention alternatives. Methods The mathematical model illustrates the natural history of ESCC as a sequence of transitions among health states, including the primary health states (e.g., normal mucosa, precancerous lesions, and undetected and detected cancer). Using established calibration approaches, the parameter sets related to progression rates between health states were optimized to lead the model outputs to match the observed data (specifically, the prevalence of precancerous lesions and incidence of ESCC from the published literature in Chinese high-risk regions). As illustrative examples of clinical and policy application, the calibrated and validated model retrospectively simulate the potential benefit of two reported ESCC screening programs. Results Nearly 1,000 good-fitting parameter sets were identified from 1,000,000 simulated sets. Model outcomes had sufficient calibration fit to the calibration targets. Additionally, the verification analyses showed reasonable external consistency between the model-predicted effectiveness of ESCC screening and the reported data from clinical trials. Conclusions This parameterized mathematical model offers a tool for future research investigating benefits, costs, and cost-effectiveness related to ESCC prevention and treatment.
Highlights
The global disease burden contributed by esophageal cancer is approximately 10 million disability-adjusted life-years (DALYs) [1], which is ranked 11th worldwide and 6th in China for all neoplasms [2, 3]
The aim of this study is to present the development of an esophageal squamous cell carcinoma (ESCC) policy model, including a comprehensive framework of the model structure with the best available clinical and epidemiological inputs, calibration techniques and endpoints, and model validation
The model was fit to our calibration targets using 952 good-fitting parameter sets, precancerous lesions prevalences, and ESCC incidence stratified by specific age groups
Summary
The global disease burden contributed by esophageal cancer is approximately 10 million disability-adjusted life-years (DALYs) [1], which is ranked 11th worldwide and 6th in China for all neoplasms [2, 3]. Due to the late stage at diagnosis for most patients and limited treatment options, the case fatality rate of ESCC is high, and the prognosis is poor [5]. Identification of primary or secondary prevention strategies to reduce the disease burden of ESCC is a public health priority. From the perspective of the high-risk regions of ESCC, such as China, where approximately 40% of the world’s DALY related to esophageal cancers occur, implementation of the ESCC screening program might offer a feasible option to reduce the disease burden
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