Roberts Melissa H, Mapel Douglas W, Borrego Matthew E, Raisch Dennis W, Georgopoulos Larry, van der Goes David
Health Services Research Division, LCF Research, 2309 Renard Place SE, Suite 103, Albuquerque, NM, 87106, USA.
College of Pharmacy, University of New Mexico, Albuquerque, NM, USA.
Drugs Real World Outcomes. 2015 Jun;2(2):163-175. doi: 10.1007/s40801-015-0025-6.
Results from three observational methods for assessing effectiveness of long-acting bronchodilator therapies for reducing severe exacerbations of chronic obstructive pulmonary disease (COPD) were compared: intent-to-treat (ITT), as protocol (AP), and an as-treated analysis that utilized a marginal structural model (MSM) incorporating time-varying covariates related to treatment adherence and moderate exacerbations.
Severe exacerbation risk was assessed over a 2-year period using claims data for patients aged ≥40 years who initiated long-acting muscarinic antagonist (LAMA), inhaled corticosteroid/long-acting beta-agonist (ICS/LABA), or triple therapy (LAMA + ICS/LABA).
A total of 5475 COPD patients met inclusion criteria. Six months post-initiation, 53.5 % of patients discontinued using any therapy. The ITT analysis found an increased severe exacerbation risk for triple therapy treatment (hazard ratio [HR] 1.24; 95 % confidence interval [CI] 1.00-1.53). No increased risk was found in the AP (HR 1.00; 95 % CI 0.73-1.36), or MSM analyses (HR 1.11; 95 % CI 0.68-1.81). The MSM highlighted important associations among post-index events.
Neglecting to adjust for treatment discontinuation may produce biased risk estimates. The MSM approach is a promising tool to compare chronic disease management by illuminating relationships between treatment decisions, adherence, patient choices, and outcomes.
比较三种观察性方法评估长效支气管扩张剂疗法减少慢性阻塞性肺疾病（COPD）严重加重发作有效性的结果：意向性分析（ITT）、按方案分析（AP）以及采用纳入与治疗依从性和中度加重发作相关的随时间变化协变量的边际结构模型（MSM）的实际治疗分析。
使用年龄≥40岁开始使用长效毒蕈碱拮抗剂（LAMA）、吸入性糖皮质激素/长效β受体激动剂（ICS/LABA）或三联疗法（LAMA + ICS/LABA）患者的理赔数据，在2年期间评估严重加重发作风险。
共有5475例COPD患者符合纳入标准。开始治疗6个月后，53.5%的患者停止使用任何疗法。ITT分析发现三联疗法治疗的严重加重发作风险增加（风险比[HR] 1.24；95%置信区间[CI] 1.00 - 1.53）。在AP分析（HR 1.00；95% CI 0.73 - 1.36）或MSM分析（HR 1.11；95% CI 0.68 - 1.81）中未发现风险增加。MSM突出了索引后事件之间的重要关联。
忽略对治疗中断进行调整可能会产生有偏差的风险估计。MSM方法是一种很有前景的工具，通过阐明治疗决策、依从性、患者选择和结果之间的关系来比较慢性病管理。
