Institute of Pharmaceutical Medicine (ECPM), University of Basel, Basel, Switzerland.
Pharmaceutical Care Research Group, School of Pharmacy, University College Cork, Cork University Hospital, Cork, Ireland.
PLoS One. 2022 Apr 11;17(4):e0265507. doi: 10.1371/journal.pone.0265507. eCollection 2022.
Inappropriate polypharmacy has been linked with adverse outcomes in older, multimorbid adults. OPERAM is a European cluster-randomized trial aimed at testing the effect of a structured pharmacotherapy optimization intervention on preventable drug-related hospital admissions in multimorbid adults with polypharmacy aged 70 years or older. Clinical results of the trial showed a pattern of reduced drug-related hospital admissions, but without statistical significance. In this study we assessed the cost-effectiveness of the pharmacotherapy optimisation intervention.
We performed a pre-planned within-trial cost-effectiveness analysis (CEA) of the OPERAM intervention, from a healthcare system perspective. All data were collected within the trial apart from unit costs. QALYs were computed by applying the crosswalk German valuation algorithm to EQ-5D-5L-based quality of life data. Considering the clustered structure of the data and between-country heterogeneity, we applied Generalized Structural Equation Models (GSEMs) on a multiple imputed sample to estimate costs and QALYs. We also performed analyses by country and subgroup analyses by patient and morbidity characteristics.
Trial-wide, the intervention was numerically dominant, with a potential cost-saving of CHF 3'588 (95% confidence interval (CI): -7'716; 540) and gain of 0.025 QALYs (CI: -0.002; 0.052) per patient. Robustness analyses confirmed the validity of the GSEM model. Subgroup analyses suggested stronger effects in people at higher risk.
We observed a pattern towards dominance, potentially resulting from an accumulation of multiple small positive intervention effects. Our methodological approaches may inform other CEAs of multi-country, cluster-randomized trials facing presence of missing values and heterogeneity between centres/countries.
不适当的多种药物治疗与老年多病成年人的不良结局有关。OPERAM 是一项欧洲集群随机试验，旨在测试一种结构化药物治疗优化干预措施对 70 岁或以上患有多种药物治疗的多病成年人的可预防药物相关住院治疗的影响。该试验的临床结果显示药物相关住院治疗减少的趋势，但无统计学意义。在这项研究中，我们评估了药物治疗优化干预的成本效益。
我们从医疗保健系统的角度对 OPERAM 干预措施进行了预先计划的试验内成本效益分析（CEA）。除了单位成本外，所有数据均在试验中收集。QALYs 通过应用德国交叉评估算法将基于 EQ-5D-5L 的生活质量数据转换为 QALYs。考虑到数据的聚类结构和国家间的异质性，我们在多个插补样本上应用广义结构方程模型（GSEM）来估计成本和 QALYs。我们还按国家进行了分析，并按患者和发病特征进行了亚组分析。
在整个试验范围内，干预措施具有数值优势，潜在节省 CHF 3'588（95%置信区间（CI）：-7'716；540），每位患者增加 0.025 QALYs（CI：-0.002；0.052）。稳健性分析证实了 GSEM 模型的有效性。亚组分析表明，高风险人群的效果更强。
我们观察到一种优势模式，可能是由于多个小的积极干预效果的积累。我们的方法可能为面临缺失值和中心/国家之间异质性的多国集群随机试验的其他 CEA 提供信息。
