Supplementary materials: Early-stage hepatocellular carcinoma screening in patients with chronic hepatitis B in China: a cost–effectiveness analysis

These are peer-reviewed supplementary materials for the article 'Early-stage hepatocellular carcinoma screening in patients with chronic hepatitis B in China: a cost–effectiveness analysis' published in the Journal of Comparative Effectiveness Research.
Supplementary material 1Supplementary material 2Supplementary material 3Aim: To evaluate the cost–effectiveness of seven screening strategies for chronic hepatitis B (CHB) patients in China. Methods: A discrete event simulation model combining a decision tree and Markov structure was developed to simulate a CHB cohort aged≥40 years on a lifetime horizon and evaluate the costs and health outcomes (quality-adjusted life years [QALYs] gained) of ultrasonography (US), alpha-fetoprotein (AFP), protein induced by vitamin K absence-II (PIVKA-II), AFP+US, AFP+PIVKA-II, GAAD (a diagnostic algorithm based on gender and age combined with results of AFP and PIVKA-II) and GAAD+US. Epidemiologic, clinical performance, utility and cost data were obtained from the literature, expert interviews and real-world data. Uncertainties on key parameters were explored through deterministic and probabilistic sensitivity analyses (DSA and PSA). Results: Compared with other strategies, GAAD+US detected the most HCC patients at early stage, and GAAD was the screening strategy with the lowest average cost per HCC case diagnosed. Using 3× China’s 2022 GDP per capita ($38,233.34) as the threshold, the three strategies of US, GAAD and GAAD+US formed a cost–effectiveness frontier. Screening with US, GAAD, or GAAD+US was associated with costs of $6110.46, $7622.05 and $8636.32, and QALYs of 13.18, 13.48 and 13.52, respectively. The ICER of GAAD over US was $4993.39/QALY and the ICER of GAAD+US over GAAD was $26,691.45/QALY, which was less than 3× GDP per capita. Both DSA and PSA proved the stability of the results. Conclusion: GAAD+US was the most cost-effective strategy for early HCC diagnosis among CHB patients which could be considered as the liver cancer screening scheme for the high-risk population in China.

本内容为发表于《比较疗效研究期刊》（Journal of Comparative Effectiveness Research）的论文《中国慢性乙型肝炎患者早期肝细胞癌筛查：成本效用分析》的同行评议补充材料。
补充材料1、补充材料2、补充材料3。
研究目的：评估中国慢性乙型肝炎（chronic hepatitis B, CHB）患者的7种筛查策略的成本效用比。
研究方法：构建结合决策树与马尔可夫（Markov）结构的离散事件模拟模型，以模拟年龄≥40岁的慢性乙型肝炎患者队列的终生病程，评估超声检查（ultrasonography, US）、甲胎蛋白（alpha-fetoprotein, AFP）、维生素K缺乏或拮抗剂-II诱导蛋白（protein induced by vitamin K absence-II, PIVKA-II）、AFP联合US、AFP联合PIVKA-II、GAAD（基于性别与年龄结合AFP及PIVKA-II检测结果的诊断算法）以及GAAD联合US共7种筛查策略的成本与健康产出（获得的质量调整生命年[quality-adjusted life years, QALYs]）。
流行病学、临床效能、效用及成本数据均来自文献、专家访谈与真实世界数据。
通过确定性敏感性分析（deterministic sensitivity analysis, DSA）与概率敏感性分析（probabilistic sensitivity analysis, PSA）对关键参数的不确定性进行探讨。
研究结果：相较于其余策略，GAAD联合US可检出最多的早期肝细胞癌患者，且GAAD是每确诊1例肝细胞癌平均成本最低的筛查策略。以3倍中国2022年人均国内生产总值（gross domestic product, GDP，$38,233.34）作为阈值时，超声检查、GAAD以及GAAD联合US这3种策略构成了成本效用前沿。采用超声检查、GAAD、GAAD联合US进行筛查的成本分别为6110.46美元、7622.05美元与8636.32美元，对应的质量调整生命年分别为13.18、13.48与13.52。GAAD相较于超声检查的增量成本效用比（incremental cost-effectiveness ratio, ICER）为4993.39美元/QALY，GAAD+US相较于GAAD的增量成本效用比为26691.45美元/QALY，该值低于3倍人均GDP。确定性敏感性分析与概率敏感性分析均证实了研究结果的稳定性。
研究结论：GAAD联合US是慢性乙型肝炎患者早期肝细胞癌诊断中成本效用比最优的策略，可作为中国高危人群的肝癌筛查方案予以推广应用。