Exploring the cost-effectiveness of Helicobacter pylori screening to prevent gastric cancer in China in anticipation of clinical trial results

Abstract

Gastric cancer is the second leading cause of cancer-related deaths worldwide. Treatment for Helicobacter pylori infection, the leading causal risk factor, can reduce disease progression, but the long-term impact on cancer incidence is uncertain. Using the best available data, we estimated the potential health benefits and economic consequences associated with H. pylori screening in a high-risk region of China. An empirically calibrated model of gastric cancer was used to project reduction in lifetime cancer risk, life-expectancy and costs associated with (i) single lifetime screening (age 20, 30 or 40); (ii) single lifetime screening followed by rescreening individuals with negative results and (iii) universal treatment for H. pylori (age 20, 30 or 40). Data were from the published literature and national and international databases. Screening and treatment for H. pylori at age 20 reduced the mean lifetime cancer risk by 14.5% (men) to 26.6% (women) and cost less than $1,500 per year of life saved (YLS) compared to no screening. Rescreening individuals with negative results and targeting older ages was less cost-effective. Universal treatment prevented an additional 1.5% to 2.3% of risk reduction, but incremental cost-effectiveness ratios exceeded $2,500 per YLS. Screening young adults for H. pylori could prevent one in every 4 to 6 cases of gastric cancer in China and would be considered cost-effective using the GDP per capita threshold. These results illustrate the potential promise of a gastric cancer screening program and provide rationale for urgent clinical studies to move the prevention agenda forward.

Figure 1

Model structure of gastric cancer natural history. The model simulates the natural history of gastric carcinogenesis through a series of health states (normal gastric mucosa, chronic nonatrophic gastritis, gastric atrophy, intestinal metaplasia, dysplasia and gastric cancer). Each month, individuals can progress and regress among the health states and face age-dependent risks of dying from other causes. H. pylori-infected individuals face higher probabilities of progressing to gastritis and atrophy. Not shown are unique health states, which were defined to distinguish individuals with H. pylori infection and gastric cancer detected through symptoms, and the dead state.

Figure 2

Comparison of model output to epidemiologic data on prevalence of precancerous lesions and gastric cancer incidence for 50 good-fitting parameter sets for men. Model output for precancerous lesions prevalence are depicted in the top rows and for gastric cancer incidence in the bottom row. Bold lines indicate 95% confidence intervals of age-specific prevalence or incidence data. Non-bold lines depict model output for 50 randomly-selected good-fitting parameter sets. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 3

Sensitivity analysis on select variables for men. The X-axis shows the effect of changes in selected variables on the incremental cost-effectiveness ratio ($/YLS) for H. pylori screening once among men. The Y-axis shows the selected model variables. Values in parentheses are the upper and lower bounds used in the sensitivity analysis; the shaded bars indicate the variation in the cost-effectiveness ratio caused by changes in the value of the indicated variable while all other variables were held constant. The vertical dashed line indicates the incremental cost-effectiveness ratio for the base case. The solid line indicates an implied cost-effectiveness threshold using the gross domestic product (GDP) per capita in China.

Figure 4

Optimal strategy by cost-effectiveness threshold and H. pylori seroprevalence. Top 2 graphs depict optimal strategy for men and women given the 3-times the GDP per capita cost-effectiveness threshold ($5,400). Lower 2 graphs depict optimal strategy given the 1-times GDP per capita threshold ($1,700).

Figure 5

Sensitivity analysis on treatment effectiveness for gastritis. If treatment for H. pylori reduced disease progression for gastritis only (i.e. no effect on atrophy), the mean reduction in gastric cancer incidence ranged from 0% (RR = 1; no effect) to 42% (RR = 0; halt progression entirely). Solid line indicates the mean reduction among 50 good-fitting parameter sets. Shaded area indicates the range.

Figure 6

Two-way sensitivity analysis on treatment effectiveness and cost. H. pylori screening once would be considered cost-effective given commonly-used thresholds if treatment reduced disease progression to atrophy by more than 40% (RR = 0.6), even if antibiotic costs were 3-fold higher than base case estimates. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]