Arènes - UMR 6051, RSMS (Recherche sur les Services et Management en Santé) - U 1309, Univ Rennes, EHESP, CNRS, Inserm, Rennes, France.
Univ Rennes, CHU Rennes, Investigation Clinique de Rennes)], CIC 1414 [(Centre d, 35000, InsermRennes, France.
BMC Med Res Methodol. 2022 May 30;22(1):155. doi: 10.1186/s12874-022-01623-8.
Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies.
Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed.
Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption.
This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.
那他珠单抗和芬戈莫德被用作复发缓解型多发性硬化症的高效治疗药物。几项比较这两种药物的观察性研究使用了不同的方法来控制治疗适应症偏倚和处理删失，结果存在差异。本实证研究的目的是阐明因果推理方法对比较有效性研究结果的影响。
合并了来自三个观察性多发性硬化症登记处（MSBase、丹麦多发性硬化症登记处和法国 OFSEP 登记处）的数据。研究了四个临床结局。使用倾向评分对比较组进行匹配或加权，以估计治疗组的平均治疗效果或整个人群的平均治疗效果。在意向治疗和方案框架下进行分析。还评估了阳性假设的影响。
总体而言，纳入了 5148 例复发缓解型多发性硬化症患者。在这个样本量大的研究中，估计值的 95%置信区间广泛重叠。倾向评分加权和倾向评分匹配程序得出了一致的结果。在整个人群的平均治疗效果和治疗组的平均治疗效果估计之间观察到一些差异。意向治疗分析比方案框架分析更为保守。违反阳性假设会导致结局和倾向评分出现最明显的不规则。
这项应用研究阐明了方法学决策对多发性硬化症治疗的比较有效性研究结果的影响。根据我们的结果，在研究具有足够效力、模型正确指定且满足阳性假设的情况下，使用倾向评分匹配或倾向评分加权获得的结论没有实质性差异。
