Angus Derek C, Clermont Gilles, Watson R Scott, Linde-Zwirble Walter T, Clark Reese H, Roberts Mark S
Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Laboratory, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Pediatrics. 2003 Dec;112(6 Pt 1):1351-60. doi: 10.1542/peds.112.6.1351.
Two recent randomized controlled trials (RCTs) reported that inhaled nitric oxide (iNO) decreased the incidence of extracorporeal membrane oxygenation (ECMO) or death in term and near-term newborns with hypoxic respiratory failure. Our objective was to estimate the cost-effectiveness ratio of iNO in this population.
We studied 1000 simulation cohorts (n = 483 for each cohort) of term/near-term newborns with hypoxemic respiratory failure. We conducted our study following US Public Health Service Panel on Cost-Effectiveness in Health and Medicine guidelines, adopting the US societal perspective. We constructed a decision tree reflecting iNO use, subsequent ECMO use, death, and long-term neurologic and respiratory morbidity in survivors, as determined from the combined outcomes of the 2 RCTs (n = 483). We estimated costs on the basis of length-of-stay data for the initial episode of care from 1 of the RCTs, unit costs from administrative data sets, and current pricing for iNO. We ran a Monte Carlo simulation to generate estimates of differences in costs and effects at 1 year, along with the stochastic uncertainty around these estimates. We expressed effects as quality-adjusted survival, assuming quality of life = 1 with no comorbidity, 0.7 with 1 comorbidity, and 0.49 (0.7 x 0.7) with 2 comorbidities. We constructed a base case, in which iNO was initiated at tertiary care ECMO centers (mimicking the RCTs) and a Public Health Service Panel on Cost-effectiveness in Health and Medicine reference case, in which iNO was initiated at the local hospital before transfer (mimicking real-world practice). We exposed our assumptions to a sensitivity analysis.
Direct application of the trial results (base case) suggested that iNO was both more effective and cheaper (cost savings of 1880 dollars per case despite acquisition costs of 5150 dollars, predominantly as a result of decreased need for ECMO), with 84.6% probability that the cost-effectiveness ratio was better than 100,000 dollars per quality-adjusted life-year. Under the reference case, iNO was also more effective (though slightly less so) and was even cheaper (cost savings of 4400 dollars per case), with 71.6% probability that iNO was cheaper and more effective and 91.6% probability that the cost effectiveness ratio was better than 100,000 dollars per quality-adjusted life-year. Sensitivity analyses showed these estimates to be sensitive to patient selection and the price of iNO but insensitive to assumptions regarding quality of life.
From a US societal perspective, iNO has a favorable cost-effectiveness profile when initiated either at ECMO centers or at local hospitals in term/near-term neonates with hypoxemic respiratory failure.
两项近期的随机对照试验（RCT）报告称，吸入一氧化氮（iNO）可降低患有低氧性呼吸衰竭的足月儿和近足月儿体外膜肺氧合（ECMO）的发生率或死亡率。我们的目的是评估iNO在该人群中的成本效益比。
我们研究了1000个模拟队列（每个队列n = 483）的患有低氧血症性呼吸衰竭的足月儿/近足月儿。我们按照美国公共卫生服务健康与医学成本效益小组的指南进行研究，采用美国社会视角。我们构建了一个决策树，反映iNO的使用、随后的ECMO使用、死亡以及幸存者的长期神经和呼吸疾病，这是根据两项RCT（n = 483）的综合结果确定的。我们根据其中一项RCT首次护理期间的住院时间数据、行政数据集的单位成本以及iNO的当前定价来估算成本。我们进行了蒙特卡洛模拟，以生成1年时成本和效果差异的估计值，以及这些估计值周围的随机不确定性。我们将效果表示为质量调整后的生存率，假设无合并症时生活质量 = 1，有1种合并症时为0.7，有2种合并症时为0.49（0.7×0.7）。我们构建了一个基础案例，即iNO在三级护理ECMO中心启动（模拟RCT），以及一个美国公共卫生服务健康与医学成本效益小组的参考案例，即iNO在转运前在当地医院启动（模拟实际临床实践）。我们对我们的假设进行了敏感性分析。
直接应用试验结果（基础案例）表明，iNO既更有效又更便宜（尽管购置成本为5150美元，但每例节省成本1880美元，主要是由于对ECMO的需求减少），成本效益比优于每质量调整生命年100,000美元的概率为84.6%。在参考案例下，iNO同样更有效（尽管效果稍差）且甚至更便宜（每例节省成本4400美元），iNO更便宜且更有效的概率为71.6%，成本效益比优于每质量调整生命年100,000美元的概率为91.6%。敏感性分析表明，这些估计值对患者选择和iNO价格敏感，但对生活质量假设不敏感。
从美国社会视角来看，对于患有低氧血症性呼吸衰竭的足月儿/近足月儿，在ECMO中心或当地医院启动iNO时，其成本效益情况良好。
