Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA.
Global Biostatistics, Amgen Inc., Thousand Oaks, CA, USA.
Osteoporos Int. 2017 Oct;28(10):2893-2901. doi: 10.1007/s00198-017-4129-6. Epub 2017 Jul 6.
Due to the suboptimal persistence to osteoporosis (OP) treatment, factors triggering treatment discontinuation/switching may be causing time-varying confounding. BP treatment was associated with the risk of overall infection in opposite directions in the unweighted Cox model versus the weighted MSM. The discrepancy of effect estimates for overall infection in the MSM suggested there may be time-varying confounding.
Due to the suboptimal persistence to osteoporosis (OP) treatment, factors triggering treatment discontinuation/switching may be affected by prior treatment and confound the subsequent treatment effect, causing time-varying confounding.
In a US insurance database, the association between joint treatment of bisphosphonates (BP) and other OP medication and the incidence of infections among postmenopausal women was assessed using a marginal structural model (MSM). Stabilized weights were estimated by modeling treatment and censoring processes conditioning on past treatment, and baseline and time-varying covariates.
BP treatment was associated with the risk of overall infection in opposite directions in the unweighted Cox model {incidence rate ratio [IRR] [95% confidence interval (CI)] = 1.15 [1.14-1.17]} versus the weighted MSM [IRR (95% CI) = 0.79 (0.77-0.81)], but was consistently associated with a lower risk of serious infection in both the unweighted Cox model [IRR (95% CI] = 0.79 (0.78-0.81)) and the weighted MSM [IRR (95% CI) = 0.71 (0.68-0.75)]. Similar results were found when current and past treatments were simultaneously assessed.
The discrepancy of effect estimates for overall but not serious infection comparing unweighted models and MSM suggested analyses of composite outcomes with a wide range of disease severity may be more susceptible to time-varying confounding.
由于骨质疏松症（OP）治疗的持续性不理想，导致治疗中断/转换的因素可能会引起随时间变化的混杂。非加权 Cox 模型中 BP 治疗与总体感染风险呈相反方向相关，而加权 MSM 则相反。MSM 中总体感染的效应估计值存在差异，表明可能存在随时间变化的混杂。
在一项美国保险数据库中，使用边缘结构模型（MSM）评估了双膦酸盐（BP）与其他 OP 药物联合治疗与绝经后妇女感染发生率之间的关系。通过对治疗和终止过程建模，基于过去的治疗、基线和随时间变化的协变量来估计稳定权重。
在非加权 Cox 模型中，BP 治疗与总体感染风险呈相反方向相关（发生率比[IRR] [95%置信区间（CI）] = 1.15 [1.14-1.17]），而在加权 MSM 中则呈相反方向相关（IRR [95% CI] = 0.79 [0.77-0.81]），但在非加权 Cox 模型和加权 MSM 中均与严重感染风险降低相关（IRR [95% CI] = 0.79 [0.78-0.81]）和加权 MSM [IRR（95%CI）= 0.71（0.68-0.75）]。当同时评估当前和过去的治疗时，也得到了类似的结果。
非加权模型和 MSM 之间整体但非严重感染的效应估计值存在差异，表明对疾病严重程度范围较广的复合结局进行分析可能更容易受到随时间变化的混杂。
