We constructed a Markov model to perform a cost-effectiveness analysis to evaluate the economic benefits of incorporating H pylori testing and eradication therapy into the existing endoscopy-based NCSP. Markov models can track long-term progression of diseases with complex progression, such as cancer, so they are widely used in studies to predict long-term follow-up cost-effectiveness for chronic diseases [11].

We referenced a previously published Markov model for the economic evaluation of gastric cancer screening in Korea, modifying it to focus on H pylori infection [12]. Therefore, the cancer screening–related data input into the model were based on the cancer screening and registration data in Korea as used in Bae et al [12]. Other epidemiological indicators were reviewed by multiple expert review meetings to use real-world data as much as possible. This study is being conducted with reference to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) framework (Multimedia Appendix 1).

The two main strategies being compared for cost-effectiveness are (1) a strategy in which individuals undergo endoscopy every 2 years starting at the age of 40 years (conventional screening), and (2) a strategy in which individuals receive both endoscopy and H pylori testing with eradication therapy at the age of 40 years followed by continuous endoscopy thereafter. Furthermore, we will conduct a comparative analysis by varying the age at which H pylori screening is performed.

The Markov simulation model was constructed for a hypothetical population starting at 40 years, with cycles repeated until death or up to a maximum age of 120 years, for a total of 81 cycles; 1 cycle indicates 1 year. The main outcome presents the estimated cumulative costs and quality-adjusted life-years (QALYs) for a person’s entire life cycle. At the beginning of the cohort, individuals are categorized as either noninfected or infected with H pylori, and those who successfully undergo eradication therapy transition to the eradicated state. Reinfection is possible even in the eradicated state, and it is assumed that natural eradication does not occur and that infection is only eradicated by treatment. In all states, individuals may transition to either early or advanced gastric cancer. Upon cancer onset, patients remain in a cancer-cured state after a 5-year follow-up period. Figure 1 shows the Markov model. This study aims to verify whether introducing H pylori testing and eradication therapy is cost-effective, and to determine whether it reduces the risk of developing early gastric cancer compared to conventional screening.

In this study, the parameters required for the model are categorized as related to epidemiology, cost, or screening. Epidemiological parameters include the prevalence of H pylori infection, annual infection rate, reinfection rate, probability of progression to cancer, and mortality rate (among the general population and patients with cancer), which can be obtained from sources such as the National Health Insurance Service (NHIS) database, national statistics, and prior studies [3,13-20]. Cost parameters include the costs associated with H pylori testing and eradication therapy (such as biopsy costs and medication costs), the cost of endoscopy screening, and the cost of cancer treatment. Following the economic evaluation guideline of the Health Insurance Review and Assessment Service, we take a health care system perspective, so only direct costs, excluding transportation and caregiving expenses, are considered. Cost data are obtained through the National Health Insurance Medical Service Benefit Costs, the price by main ingredient of pharmaceutical products, and the NCSP guidelines [21]. Finally, the screening parameters include the rate of H pylori testing and rate of eradication therapy if the test result is positive, which is assumed to be 100%. The sensitivity and specificity of the H pylori testing and eradication success rates are derived from prior studies [22-25]. The endoscopy screening rate, sensitivity, and specificity are obtained from a combined dataset of the Central Cancer Registry Database and the National Cancer Screening Database of the NHIS. A list of these parameters is presented in Table 1.

An individual receives a rapid urea test at the age of 40 years during endoscopy as part of the NCSP. The patient receives eradication therapy if the urease test results are positive. The eradication regimen consists of a clarithromycin-based triple therapy regimen (twice-daily doses of 40 mg esomeprazole, 1 g amoxicillin, and 500 mg clarithromycin) for 14 days.

The main outcome of this study is the incremental cost-utility ratio (ICUR). This is calculated by dividing the incremental cost between the two strategies by incremental utility, represented by the QALYs accumulated over all cycles for each strategy. The utility weight for each health state is aggregated to determine the QALYs, with utility weights for the general population obtained from the National Health and Nutrition Examination Survey Database and those for H pylori–infected individuals and cancer patients obtained from a prior study [26].

A probabilistic sensitivity analysis will be performed to test the uncertainty of the cost-effectiveness results. This involves running the Markov simulation 100,000 times to verify the consistency and robustness of the results. Additionally, a one-way sensitivity analysis will be conducted to identify the variables that have the most significant impact on the results, observing how the cost-effectiveness outcome changes when the values of these variables vary within a specific range.

In the base-case analysis, the H pylori testing and eradication therapy implementation rates are assumed to be 100%. However, when these rates vary, the cost-effectiveness of different scenarios can be compared. Therefore, the analysis identifies which scenario, with specific values for testing and eradication therapy implementation rates, is the most cost-effective.

This study will analyze and synthesize previously published data and is therefore exempt from institutional review board approval from the National Cancer Center.

This study aims to provide evidence for the cost-effectiveness of integrating H pylori screening into the NCSP to reduce gastric cancer risk. We are planning to determine the most cost-effective methods of H pylori screening based on age at screening and the frequency of screening. We expect that our study will also identify factors that contribute to improving cost-effectiveness in the National Gastric Cancer Screening Program. The anticipated findings of our study have the potential to significantly impact gastric cancer screening programs. By examining the cost-effectiveness of H pylori screening, we aim to highlight the importance of H pylori in preventing gastric cancer. This should lead to a paradigm shift in gastric cancer screening programs, from early detection to primary prevention.

There are expected limitations to our study, such as the age at H pylori screening. As the purpose of our study is to incorporate H pylori screening into the nationwide gastric cancer screening program, we will examine the cost-effectiveness of screening starting from the age of 40 years, which is when the NCSP begins. Future studies are needed to determine whether early screening for H pylori is more cost-effective. Stratified screening based on the risk of gastric cancer development will not be examined in our study due to the lack of data on this topic. We plan to examine whether extending the endoscopic screening interval is cost-effective in patients who have received eradication therapy.

Our cost-effectiveness analysis represents a crucial step toward understanding and promoting the most effective method for gastric cancer screening. We expect to provide evidence for the effectiveness of H pylori screening for gastric cancer prevention. The results of our study could serve as a valuable reference for the development of gastric cancer screening programs in other countries.

We plan to examine whether introducing H pylori testing and eradication therapy into the NCSP is a more cost-effective strategy than conventional endoscopy-based cancer screening for reducing the risk of gastric cancer. Our study will also examine the optimal age for H pylori screening as well as the optimal screening frequency for H pylori.