Base case results (discounted)—Children.

Background
Cochlear Implant (CI) has been shown to improve speech comprehension, sound localization and tinnitus in adults with Single-Sided-Deafness (SSD) compared to standard treatment currently available in the Dutch setting such as a CROS (Contralateral Routing of Signals) hearing device or a BCD (Bone Conduction Device). Also, for the pediatric population with SSD, CI has shown to be clinically meaningful. Because currently no information is available on the health economic effects of CI in adults and children with SSD in the Netherlands, a cost-utility analysis was conducted.
Methods
We developed a Markov cohort model, for both the adult and pediatric SSD population, with three states: implant, no implant, and dead. CI was compared with the Bone Conduction Device (BCD) treatment, requiring surgery and no specific treatment. The time horizon of the model was lifelong, costs were discounted with 3% and effects with 1.5%. A societal perspective was taken, including productivity costs in the analysis, with costing data based on publicly available prices for the Netherlands. Values for clinical outcome parameters, i.e. hearing gain, and event probabilities were based on existing literature. Deterministic and probabilistic sensitivity analyses as well as scenario analyses were performed to outline uncertainty of individual and combined parameters.
Results
Mean per patient costs for CI in the adult population were €194,051 (95%-CrI €177,274 to €211,108) compared to the total costs of €185,310 (95%-CrI €182,367 to €194,142) for BCD resulting in a cost difference of €8,826 (95%-CrI -€5,020 to €18,252). Compared to no treatment, the cost difference was -€25,089 (95%-CrI -€31,678 to -€6,003). Adults who were treated with CI gained 18.41 (95%-CrI 18.07 to 18.75) quality adjusted life years (QALY) whereas BCD patients gained 15.81 QALYs (95%-CrI 15.53 to 16.10), a difference of 2.60 QALYs (95%-CrI 2.15 to 3.05). The Incremental Cost Effectiveness Ratio (ICER) for adults with CI was determined to be €3,494/QALY gained. Patient without treatment gained 13.46 QALY (95%-CrI 13.20 to 13.73), a difference of 4.95 (95%-CrI 4.87 to 5.01) resulting in CI dominating no treatment. The ICER remained below the Dutch threshold of €20,000/QALY. The probabilistic sensitivity analyses confirmed the results. For children, CI dominated when compared to BCD and when compared to no treatment. Compared to BCD, CI led to a cost saving of €29,611 (95%-CrI -€126,800 to €54,375) and compared to no treatment, CI resulted in a cost saving of €57,658 (95%-CrI -€146,687 to €5,919). The incremental QALY gain compared to BCD was 7.22 (95%-CrI 4.19 to 8.55) and 26.03 (95%-CrI 20.82 to 31.06) compared to no treatment.
Conclusions
Based on the results of this health economic evaluation with a Markov cohort model, it is very likely that CI is cost-effective compared to BCD and to no treatment in the Dutch adult and pediatric population with SSD. In both populations the ICER was below the Dutch cost-effectiveness threshold of €20,000/QALY.

研究背景
人工耳蜗植入术（Cochlear Implant, CI）已被证实，相较于荷兰当前主流的标准治疗方案（如对侧信号传导（Contralateral Routing of Signals, CROS）助听器或骨传导装置（Bone Conduction Device, BCD）），可改善单侧耳聋（Single-Sided Deafness, SSD）成人患者的言语理解能力、声音定位能力及耳鸣症状。针对SSD患儿群体，CI治疗同样展现出具有临床意义的获益。鉴于目前荷兰地区尚无针对成人与儿童SSD患者接受CI治疗的卫生经济学效应相关研究数据，本研究开展了成本效用分析。

研究方法
本研究针对成人及儿童SSD群体构建马尔可夫队列模型（Markov cohort model），模型包含三种状态：已植入人工耳蜗、未植入人工耳蜗以及死亡。将CI与需手术干预的骨传导装置（BCD）治疗及无特殊治疗方案进行对比。模型的时间跨度为终身，成本按3%进行贴现，健康产出按1.5%进行贴现。本研究采用社会视角开展分析，纳入生产力成本相关内容，成本数据基于荷兰公开可得的价格标准。临床结局参数（如听力增益）及事件发生概率的取值均来自已发表文献。此外，本研究开展了确定性敏感性分析、概率敏感性分析及场景分析，以明确单个及组合参数的不确定性范围。

研究结果
成人SSD患者接受CI治疗的人均成本为194051欧元（95%可信区间[CrI]：177274~211108欧元），而接受BCD治疗的患者人均总成本为185310欧元（95%CrI：182367~194142欧元），二者成本差值为8826欧元（95%CrI：-5020~18252欧元）。相较于无特殊治疗方案，CI治疗的成本差为-25089欧元（95%CrI：-31678~-6003欧元）。
接受CI治疗的成人患者质量调整生命年（quality adjusted life years, QALY）为18.41（95%CrI：18.07~18.75），而接受BCD治疗的患者为15.81 QALY（95%CrI：15.53~16.10），二者QALY差值为2.60（95%CrI：2.15~3.05）。成人群体中CI治疗的增量成本效果比（Incremental Cost Effectiveness Ratio, ICER）为3494欧元/每获得的QALY。未接受治疗的成人患者QALY为13.46（95%CrI：13.20~13.73），CI治疗相较于无治疗方案的QALY差值为4.95（95%CrI：4.87~5.01），即CI治疗显著优于无治疗方案。成人群体中CI治疗的ICER低于荷兰设定的20000欧元/QALY的成本效果阈值。概率敏感性分析验证了上述结果。
针对儿童群体，CI治疗相较于BCD治疗及无治疗方案均表现出成本效果优势。相较于BCD治疗，CI治疗可节省29611欧元（95%CrI：-126800~54375欧元）；相较于无治疗方案，CI治疗可节省57658欧元（95%CrI：-146687~5919欧元）。相较于BCD治疗，CI治疗的增量QALY增益为7.22（95%CrI：4.19~8.55）；相较于无治疗方案，增量QALY增益为26.03（95%CrI：20.82~31.06）。

研究结论
基于本研究构建的马尔可夫队列模型的卫生经济学评估结果，在荷兰SSD成人与儿童群体中，CI治疗相较于BCD治疗及无治疗方案均具有较高的成本效益。两个群体中CI治疗的ICER均低于荷兰设定的20000欧元/QALY的成本效果阈值。