Spencer Michael, Briggs Andrew H, Grossman Ronald F, Rance Laureen
Global Health Outcomes, GlaxoSmithKline Research & Development, Greenford, Middlesex, UK.
Pharmacoeconomics. 2005;23(6):619-37. doi: 10.2165/00019053-200523060-00008.
To develop a Markov model that allows the cost effectiveness of interventions in patients with chronic obstructive pulmonary disease (COPD) to be estimated, and to apply the model to investigate the cost effectiveness of an inhaled corticosteroid/long-acting beta(2)-adrenoceptor agonist (beta(2)-agonist) combination (salmeterol/fluticasone propionate) versus usual care.
A Markov model consisting of four mutually exclusive disease states was constructed (mild, moderate and severe disease, and death). The transition probabilities of disease progression (for smokers and ex-smokers) and death were derived from the published medical literature. The model outputs were costs, exacerbations, survival, QALYs and cost effectiveness. The model was made fully probabilistic to reflect the joint uncertainty in the model parameters. Efficacy data for the combination of inhaled salmeterol/fluticasone propionate 50/500microg twice daily in poorly reversible COPD patients with a history of exacerbations were obtained from the 1-year TRISTAN (TRial of Inhaled STeroids ANd long-acting beta-agonists) study and applied to the model, based on patient profiles representative of COPD clinical trials.
According to the model, the mean life expectancy with usual care alone (placebo group) was 8.95 years, which decreased to 4.08 QALYs once adjusted for quality and discounted, at a lifetime discounted cost of Can 16,415 dollars per patient (year 2002 values). Assuming that salmeterol/fluticasone propionate reduced exacerbation frequency only (base case analysis), the estimated mean survival time remained unchanged but there was an increase in the number of QALYs (4.21) for an estimated lifetime cost of Can 25,780 dollars, resulting in a cost-effectiveness ratio of Can 74,887 dollars per QALY (95% CI 21,985, 128,671) versus usual care. If a survival benefit was assumed for salmeterol/fluticasone propionate, the incremental cost per QALY was Can11,125 dollars (95% CI 8710, dominated) versus usual care. If the combination achieved around a 10% improvement in forced expiratory volume in 1 second, leading to delayed progression to more severe disease states, the benefits translated into an incremental cost per QALY of Can 49,928 dollars (95% CI 37 269, 66,006) versus usual care.
This Markov model allows, for the first time, a means of estimating the long-term cost effectiveness and cost utility of interventions for COPD. Initial evidence suggests that for patients with poorly reversible COPD and a documented history of frequent COPD exacerbations, the addition of salmeterol (a long-acting beta(2)-agonist) to fluticasone propionate (an inhaled corticosteroid) is potentially cost effective from the Canadian healthcare payer's perspective. However, the precision of this estimate will be improved when additional data are available from clinical trials such as the ongoing TORCH (TOwards a Revolution in COPD Health) study.
建立一个马尔可夫模型,用于估计慢性阻塞性肺疾病(COPD)患者干预措施的成本效益,并应用该模型研究吸入性糖皮质激素/长效β2肾上腺素能受体激动剂(β2-激动剂)联合用药(沙美特罗/丙酸氟替卡松)与常规治疗相比的成本效益。
构建一个由四个相互排斥的疾病状态组成的马尔可夫模型(轻度、中度和重度疾病以及死亡)。疾病进展(吸烟者和已戒烟者)和死亡的转移概率来自已发表的医学文献。模型输出包括成本、急性加重次数、生存率、质量调整生命年(QALYs)和成本效益。该模型进行了完全概率分析,以反映模型参数中的联合不确定性。从为期1年的TRISTAN(吸入性类固醇和长效β-激动剂试验)研究中获得了每天两次吸入50/500μg沙美特罗/丙酸氟替卡松联合用药对有急性加重病史的可逆性差的COPD患者的疗效数据,并基于代表COPD临床试验的患者资料应用于该模型。
根据该模型,仅接受常规治疗(安慰剂组)的平均预期寿命为8.95年,经质量调整和贴现后降至4.08个QALYs,每位患者的终身贴现成本为16,415加元(2002年价值)。假设沙美特罗/丙酸氟替卡松仅降低急性加重频率(基础病例分析),估计的平均生存时间保持不变,但QALYs数量增加(4.21),估计的终身成本为25,780加元,与常规治疗相比,成本效益比为每QALY 74,887加元(95%CI 21,985, 128,671)。如果假设沙美特罗/丙酸氟替卡松有生存获益,与常规治疗相比,每QALY的增量成本为11,125加元(95%CI 8710,优势明显)。如果联合用药使1秒用力呼气量提高约10%,导致进展至更严重疾病状态的时间延迟,则与常规治疗相比,每QALY的获益转化为增量成本49,928加元(95%CI 3,7269, 6,6006)。
该马尔可夫模型首次提供了一种估计COPD干预措施长期成本效益和成本效用的方法。初步证据表明,从加拿大医疗保健支付者的角度来看,对于可逆性差且有频繁COPD急性加重记录病史的患者,在丙酸氟替卡松(一种吸入性糖皮质激素)中添加沙美特罗(一种长效β2-激动剂)可能具有成本效益。然而,当从正在进行的TORCH(迈向COPD健康革命)等临床试验中获得更多数据时,这一估计的精确度将会提高。