PDF(Pubmed)
Abstract：
BACKGROUND: Resistant bacterial infections, particularly those caused by gram-negative pathogens, are associated with high mortality and economic burdens. Ceftolozane/tazobactam demonstrated efficacy comparable to meropenem in patients with ventilated hospital-acquired bacterial pneumonia in the ASPECT-NP study. One cost-effectiveness analysis in the United States revealed that ceftolozane/tazobactam was cost effective, but no Japanese studies have been conducted. Therefore, the objective of this study was to assess the cost-effectiveness of ceftolozane/tazobactam compared to meropenem for patients with ventilated hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia from a health care payer perspective.
METHODS: A hybrid decision-tree Markov decision-analytic model with a 5-year time horizon were developed to estimate costs and quality-adjusted life-years and to calculate the incremental cost-effectiveness ratio associated with ceftolozane/tazobactam and meropenem in the treatment of patients with ventilated hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia. Clinical outcomes were based on the ASPECT-NP study, costs were based on the national fee schedule of 2022, and utilities were based on published data. One-way sensitivity analysis and probabilistic sensitivity analysis were also conducted to assess the robustness of our modeled estimates.
RESULTS: According to our base-case analysis, compared with meropenem, ceftolozane/tazobactam increased the total costs by 424,731.22 yen (£2,626.96) and increased the quality-adjusted life-years by 0.17, resulting in an incremental cost-effectiveness ratio of 2,548,738 yen (£15,763.94) per quality-adjusted life-year gained for ceftolozane/tazobactam compared with meropenem. One-way sensitivity analysis showed that although the incremental cost-effectiveness ratio remained below 5,000,000 yen (£30,925) for most of the parameters, the incremental net monetary benefit may have been less than 0 depending on the treatment efficacy outcome, especially the cure rate and mortality rate for MEPM and mortality rate for CTZ/TAZ. 53.4% of the PSA simulations demonstrated that CTZ/TAZ was more cost-effective than MEPM was.
CONCLUSIONS: Although incremental cost-effectiveness ratio was below ￥5,000,000 in base-case analysis, whether ceftolozane/tazobactam is a cost-effective alternative to meropenem for ventilated hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia in Japan remains uncertain. Future research should examine the unobserved heterogeneity across patient subgroups and decision-making settings, to characterise decision uncertainty and its consequences so as to assess whether additional research is required.
METHODS: A hybrid decision-tree Markov decision-analytic model with a 5-year time horizon were developed to estimate costs and quality-adjusted life-years and to calculate the incremental cost-effectiveness ratio associated with ceftolozane/tazobactam and meropenem in the treatment of patients with ventilated hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia. Clinical outcomes were based on the ASPECT-NP study, costs were based on the national fee schedule of 2022, and utilities were based on published data. One-way sensitivity analysis and probabilistic sensitivity analysis were also conducted to assess the robustness of our modeled estimates.
RESULTS: According to our base-case analysis, compared with meropenem, ceftolozane/tazobactam increased the total costs by 424,731.22 yen (£2,626.96) and increased the quality-adjusted life-years by 0.17, resulting in an incremental cost-effectiveness ratio of 2,548,738 yen (£15,763.94) per quality-adjusted life-year gained for ceftolozane/tazobactam compared with meropenem. One-way sensitivity analysis showed that although the incremental cost-effectiveness ratio remained below 5,000,000 yen (£30,925) for most of the parameters, the incremental net monetary benefit may have been less than 0 depending on the treatment efficacy outcome, especially the cure rate and mortality rate for MEPM and mortality rate for CTZ/TAZ. 53.4% of the PSA simulations demonstrated that CTZ/TAZ was more cost-effective than MEPM was.
CONCLUSIONS: Although incremental cost-effectiveness ratio was below ￥5,000,000 in base-case analysis, whether ceftolozane/tazobactam is a cost-effective alternative to meropenem for ventilated hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia in Japan remains uncertain. Future research should examine the unobserved heterogeneity across patient subgroups and decision-making settings, to characterise decision uncertainty and its consequences so as to assess whether additional research is required.
摘要：
背景：耐药性细菌感染，特别是那些由革兰氏阴性病原体引起的，与高死亡率和经济负担有关。在ASPECT-NP研究中，头孢洛赞/他唑巴坦在通气性医院获得性细菌性肺炎患者中的疗效与美罗培南相当。在美国进行的一项成本效益分析表明，头孢特洛赞/他唑巴坦具有成本效益，但是没有日本研究。因此,本研究的目的是从医疗费用支付者的角度,评估头孢托赞/他唑巴坦与美罗培南相比对通气性医院获得性细菌性肺炎/呼吸机相关细菌性肺炎患者的成本-效果.
方法：开发了具有5年时间范围的混合决策树马尔可夫决策分析模型，以估算成本和质量调整的生命年，并计算与头孢洛扎/他唑巴坦和美罗培南治疗通气性医院获得性细菌性肺炎/呼吸机相关细菌性肺炎患者相关的增量成本效益比。临床结果基于ASPECT-NP研究，成本基于2022年的国家收费表，公用事业基于公布的数据。还进行了单向敏感性分析和概率敏感性分析，以评估我们建模估计的稳健性。
结果：根据我们的基本案例分析，与美罗培南相比，头孢托洛扎/他唑巴坦将总成本增加了424,731.22日元（2,626.96英镑），并将质量调整寿命年增加了0.17，导致每个质量调整寿命年的成本效益比增加了2,548,738日元（15,763.94英镑）头孢托扎/他唑巴坦与美罗培南相比。单向敏感性分析表明，尽管大多数参数的增量成本效益比仍低于5,000,000日元（30,925英镑），根据治疗疗效结果，净货币收益增量可能小于0，尤其是MEPM的治愈率和死亡率以及CTZ/TAZ的死亡率。53.4%的PSA模拟表明CTZ/TAZ比MEPM更具成本效益。
结论：尽管在基本情况分析中，增量成本效益比低于5,000,000元，在日本,头孢洛赞/他唑巴坦是否是美罗培南治疗通气性医院获得性细菌性肺炎/呼吸机相关细菌性肺炎的经济有效的替代药物仍不确定.未来的研究应该检查患者亚组和决策设置中未观察到的异质性，表征决策不确定性及其后果，以评估是否需要额外的研究。
方法：开发了具有5年时间范围的混合决策树马尔可夫决策分析模型，以估算成本和质量调整的生命年，并计算与头孢洛扎/他唑巴坦和美罗培南治疗通气性医院获得性细菌性肺炎/呼吸机相关细菌性肺炎患者相关的增量成本效益比。临床结果基于ASPECT-NP研究，成本基于2022年的国家收费表，公用事业基于公布的数据。还进行了单向敏感性分析和概率敏感性分析，以评估我们建模估计的稳健性。
结果：根据我们的基本案例分析，与美罗培南相比，头孢托洛扎/他唑巴坦将总成本增加了424,731.22日元（2,626.96英镑），并将质量调整寿命年增加了0.17，导致每个质量调整寿命年的成本效益比增加了2,548,738日元（15,763.94英镑）头孢托扎/他唑巴坦与美罗培南相比。单向敏感性分析表明，尽管大多数参数的增量成本效益比仍低于5,000,000日元（30,925英镑），根据治疗疗效结果，净货币收益增量可能小于0，尤其是MEPM的治愈率和死亡率以及CTZ/TAZ的死亡率。53.4%的PSA模拟表明CTZ/TAZ比MEPM更具成本效益。
结论：尽管在基本情况分析中，增量成本效益比低于5,000,000元，在日本,头孢洛赞/他唑巴坦是否是美罗培南治疗通气性医院获得性细菌性肺炎/呼吸机相关细菌性肺炎的经济有效的替代药物仍不确定.未来的研究应该检查患者亚组和决策设置中未观察到的异质性，表征决策不确定性及其后果，以评估是否需要额外的研究。
