Flexible Marginal Structural Models for Estimating the Cumulative Effect of a Time-Dependent Treatment on the Hazard: Reassessing the Cardiovascular Risks of Didanosine Treatment in the Swiss HIV Cohort Study
Flexible Marginal Structural Models for Estimating the Cumulative Effect of a Time-Dependent Treatment on the Hazard: Reassessing the Cardiovascular Risks of Didanosine Treatment in the Swiss HIV Cohort Study
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DOI：
10.1080/01621459.2013.872650
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发表时间：
2014-06-01
影响因子：
3.7
通讯作者：
Young, James
中科院分区：
文献类型：
--
作者：
Xiao, Yongling;Abrahamowicz, Michal;Young, James
自抗艾滋病毒药物不良事件数据收集（D: A: D）研究报告最近使用两种抗逆转录病毒药物阿巴卡韦（ABC）和二腺苷（DDI）与风险增加有关以来，抗逆转录病毒治疗与艾滋病毒阳性者心血管疾病（CVD）风险之间的关系一直是争论不休的主题。我们关注DDI使用的潜在影响，因为这种药物还没有像ABC那样被深入研究。我们提出了一个灵活的边际结构Cox模型和加权累积暴露模型（Cox WCE MSM），以解决在使用观察性纵向数据评估药物不良反应时遇到的两个关键挑战：(1)需要对时间依赖性治疗的累积效应进行建模；(2)需要控制时间依赖性混杂因素，这些混杂因素也可以作为过去治疗效果的中介。模拟证实，Cox WCE MSM对复杂暴露效应和时间依赖的混杂产生了准确的因果治疗效果估计。然后，我们在瑞士HIV队列研究中使用新的灵活Cox WCE MSM来评估DDI使用与心血管疾病风险之间的关系。与传统参数Cox MSM获得的不显著结果相比，我们的新Cox WCE MSM识别出由于前一年使用DDI而导致的显着的短期风险增加。本文的补充材料可在网上获得。
The association between antiretroviral treatment and cardiovascular disease (CVD) risk in HIV-positive persons has been the subject of much debate since the Data collection on Adverse events of Anti-HIV Drugs (D: A: D) study reported that recent use of two antiretroviral drugs, abacavir (ABC) and didanosine (DDI), was associated with increased risk. We focus on the potential impact of DDI use, as this drug has not been as studied intensively as ABC. We propose a flexible marginal structural Cox model with weighted cumulative exposure modeling (Cox WCE MSM) to address two key challenges encountered when using observational longitudinal data to assess the adverse effects of medication: (1) the need to model the cumulative effect of a time-dependent treatment and (2) the need to control for time-dependent confounders that also act as mediators of the effect of past treatment. Simulations confirm that the Cox WCE MSM yields accurate estimates of the causal treatment effect given complex exposure effects and time-dependent confounding. We then use the new flexible Cox WCE MSM to assess the association between DDI use and CVD risk in the Swiss HIV Cohort Study. In contrast to the nonsignificant results obtained with conventional parametric Cox MSMs, our new Cox WCE MSM identifies a significant short-term risk increase due to DDI use in the previous year. Supplementary materials for this article are available online.