Department of Health Services Research, Maastricht University, The Netherlands.
Ann Rheum Dis. 2011 Dec;70(12):2111-8. doi: 10.1136/annrheumdis-2011-200333. Epub 2011 Aug 20.
To develop a modelling framework which can simulate long-term quality of life, societal costs and cost-effectiveness as affected by sequential drug treatment strategies for ankylosing spondylitis (AS).
Discrete event simulation paradigm was selected for model development. Drug efficacy was modelled as changes in disease activity (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) and functional status (Bath Ankylosing Spondylitis Functional Index (BASFI)), which were linked to costs and health utility using statistical models fitted based on an observational AS cohort. Published clinical data were used to estimate drug efficacy and time to events. Two strategies were compared: (1) five available non-steroidal anti-inflammatory drugs (strategy 1) and (2) same as strategy 1 plus two tumour necrosis factor α inhibitors (strategy 2). 13,000 patients were followed up individually until death. For probability sensitivity analysis, Monte Carlo simulations were performed with 1000 sets of parameters sampled from the appropriate probability distributions.
The models successfully generated valid data on treatments, BASDAI, BASFI, utility, quality-adjusted life years (QALYs) and costs at time points with intervals of 1-3 months during the simulation length of 70 years. Incremental cost per QALY gained in strategy 2 compared with strategy 1 was €35,186. At a willingness-to-pay threshold of €80,000, it was 99.9% certain that strategy 2 was cost-effective.
The modelling framework provides great flexibility to implement complex algorithms representing treatment selection, disease progression and changes in costs and utilities over time of patients with AS. Results obtained from the simulation are plausible.
开发一种建模框架，该框架可以模拟强直性脊柱炎（AS）序贯药物治疗策略对长期生活质量、社会成本和成本效益的影响。
选择离散事件模拟范例来开发模型。使用基于观察性 AS 队列的统计模型，将药物疗效建模为疾病活动度（Bath 强直性脊柱炎疾病活动指数（BASDAI））和功能状态（Bath 强直性脊柱炎功能指数（BASFI））的变化，通过这些模型将成本和健康效用联系起来。使用已发表的临床数据来估计药物疗效和时间至事件。比较了两种策略：（1）五种可用的非甾体抗炎药（策略 1）和（2）与策略 1 相同加两种肿瘤坏死因子-α抑制剂（策略 2）。对 13000 名患者进行个体随访，直至死亡。对于概率敏感性分析，使用从适当概率分布中抽取的 1000 组参数进行 Monte Carlo 模拟。
该模型成功地生成了与治疗、BASDAI、BASFI、效用、质量调整生命年（QALYs）和成本有关的有效数据，时间点间隔为 1-3 个月，模拟长度为 70 年。与策略 1 相比，策略 2 每获得一个质量调整生命年的增量成本为 35186 欧元。在 80000 欧元的意愿支付阈值下，策略 2 具有 99.9%的成本效益。
该建模框架为实施代表 AS 患者治疗选择、疾病进展以及成本和效用随时间变化的复杂算法提供了极大的灵活性。模拟结果是合理的。
