ScHARR, University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, England,
Pharmacoeconomics. 2014 Feb;32(2):159-72. doi: 10.1007/s40273-013-0122-x.
Cystic fibrosis (CF) affects over 9,000 people in the UK and limits life expectancy. CF patients are susceptible to lung infections, most commonly Pseudomonas aeruginosa. Once infection is established, patients require lifetime treatment using nebulised antibiotics. Newer dry powder formulations of antibiotics may reduce treatment burden and improve compliance.
Our objective was to evaluate the cost effectiveness of (i) colistimethate sodium dry powder for inhalation (DPI) and (ii) tobramycin DPI versus nebulised tobramycin for the treatment of chronic P. aeruginosa lung infection in patients with CF from the perspective of the National Health Service (NHS) and Personal Social Services (PSS).
We developed a state transition model based on transitions between three strata of lung function measured in terms of forced expiratory volume in 1 second (FEV1) % predicted. Additional health states representing post-lung transplantation and dead are also modelled. The model structure was informed by systematic reviews of evidence concerning the plausibility of potential relationships between intermediate endpoints and final outcomes. The model assumes that treatment impacts on FEV1 trajectory, which manifest as changes in health-related quality of life. No survival benefit is assumed due to the absence of robust quantifiable evidence. Model parameters were informed by patient-level and aggregate data from two randomised controlled trials together with the best available evidence from the literature. Resource use and costs associated with drug acquisition, the management of exacerbations and reduced nebuliser maintenance were drawn from reference sources and expert opinion. Costs were valued at 2011/2012 prices. Costs and health outcomes were discounted at a rate of 3.5 %. Simple and probabilistic sensitivity analyses were undertaken, including additional analyses of Patient Access Scheme (PAS) price discounts offered by the manufacturers of both DPI products.
Colistimethate sodium DPI is expected to produce fewer quality-adjusted life-years (QALYs) than nebulised tobramycin. Based on its list price, colistimethate sodium DPI is expected to be dominated by nebulised tobramycin. When the PAS is incorporated, the incremental cost-effectiveness ratio (ICER) for colistimethate sodium DPI versus nebulised tobramycin is expected to be approximately £288,600 saved per QALY lost. Based on its current list price, the ICER for tobramycin DPI versus nebulised tobramycin is expected to be approximately £124,000 per QALY gained. When the proposed PAS is included, tobramycin DPI is expected to dominate nebulised tobramycin.
Under their list prices, neither DPI product is likely to represent good value for money for the NHS given current cost-effectiveness thresholds. The PAS discounts have a significant impact upon the economic attractiveness of both DPI products compared against nebulised tobramycin. The clinical effectiveness and cost effectiveness of the DPIs against other nebulised antibiotics, such as aztreonam and inhaled colistimethate sodium, remains unclear.
囊性纤维化（CF）影响英国超过 9000 人，并限制了预期寿命。CF 患者易患肺部感染，最常见的是铜绿假单胞菌。一旦感染确立，患者需要使用雾化抗生素进行终身治疗。新型抗生素干粉制剂可能会减轻治疗负担并提高依从性。
从英国国家医疗服务体系（NHS）和个人社会服务（PSS）的角度出发，评估（i）黏菌素硫酸沙丁胺醇干粉吸入剂（DPI）和（ii）妥布霉素 DPI 与雾化妥布霉素治疗 CF 患者慢性铜绿假单胞菌肺部感染的成本效益。
我们基于用力呼气量 1 秒（FEV1）预测百分比的三个肺功能分层之间的转移情况，开发了一种状态转移模型。还对代表肺移植后和死亡后的额外健康状态进行了建模。模型结构由关于中间终点与最终结局之间潜在关系的系统评价中有关证据的合理性所告知。该模型假设治疗会影响 FEV1 轨迹，从而影响健康相关生活质量。由于缺乏可靠的可量化证据，不假设生存获益。模型参数来自两项随机对照试验的患者水平和汇总数据，以及文献中最佳可用证据。药物获取、加重期管理和减少雾化器维护相关的资源使用和成本来自参考资料和专家意见。成本按 2011/2012 年的价格进行估值。成本和健康结果以 3.5%的贴现率贴现。进行了简单和概率敏感性分析，包括对两种 DPI 产品制造商提供的患者准入计划（PAS）价格折扣进行了额外分析。
黏菌素硫酸沙丁胺醇 DPI 预计产生的健康调整生命年（QALY）比雾化妥布霉素少。根据其定价，黏菌素硫酸沙丁胺醇 DPI 预计将被雾化妥布霉素所主导。当纳入 PAS 时，黏菌素硫酸沙丁胺醇 DPI 相对于雾化妥布霉素的增量成本效益比（ICER）预计为每损失一个 QALY 节省约 288600 英镑。根据其当前定价，妥布霉素 DPI 相对于雾化妥布霉素的 ICER 预计约为每获得一个 QALY 节省 124000 英镑。当包含提议的 PAS 时，妥布霉素 DPI 预计将主导雾化妥布霉素。
根据目前的成本效益阈值，鉴于当前的成本效益标准，两种 DPI 产品均不太可能成为 NHS 的高性价比选择。PAS 折扣对 DPI 产品相对于雾化妥布霉素的经济吸引力具有重大影响。DPIs 与其他雾化抗生素（如氨曲南和吸入黏菌素硫酸沙丁胺醇）相比的临床效果和成本效果仍不清楚。
