Pérez-Hoyos Santiago, Ferreros Inmaculada, Hernán Miguel A
Escuela Valenciana de Estudios en Salud, Valencia, España.
Gac Sanit. 2007 Jan-Feb;21(1):76-83. doi: 10.1016/s0213-9111(07)71974-x.
Standard methods to evaluate population effectiveness of treatments in observational studies have important limitations to appropriately adjust for time-dependent confounders. In this paper, we describe a recently developed methodological approach, marginal structural models (MSM), and use it to estimate the effectiveness of highly active antiretroviral therapy (HAART) on AIDS or death incidence.
We analyzed all subjects followed after 1997 as part of the GEMES project (comprised by several cohorts of HIV seroconverters in Spain) and who had not used HAART before the start of follow-up. To estimate the effect of HAART on AIDS or death incidence, we estimated the parameters of a marginal structural Cox model by fitting an inverse probability weighted logistic regression model. The estimation of the weights was based on CD4 count, time since seroconversion, sex, age, transmission category and previous treatment.
917 eligible subjects were followed for an average of 3.4 years and we observed 139 events. 42.1% of the participants received HAART during the study. The estimated rate ratio was 1.01 (95% confidence interval [CI], 0.68-1.49) using a Cox model without covariates and 0.90 (95% CI, 0.61-1.32) using a Cox model with time-dependent covariates. The causal rate ratio estimated for MSM was 0.74, (95% CI, 0.49-1.12).
The beneficial effect of HAART estimated by the MSM, but largely missed by conventional methods, is consistent with the findings of previous randomized studies. The MSM appropriately adjusted for the time-dependent covariate CD4 count, which is both a time-varying confounder and is affected by prior treatment.
在观察性研究中，评估治疗对人群有效性的标准方法在适当调整随时间变化的混杂因素方面存在重要局限性。在本文中，我们描述了一种最近开发的方法学方法，即边际结构模型（MSM），并使用它来估计高效抗逆转录病毒疗法（HAART）对艾滋病或死亡发生率的有效性。
我们分析了1997年之后随访的所有受试者，这些受试者是GEMES项目（由西班牙几个HIV血清转化者队列组成）的一部分，并且在随访开始前未使用过HAART。为了估计HAART对艾滋病或死亡发生率的影响，我们通过拟合逆概率加权逻辑回归模型来估计边际结构Cox模型的参数。权重的估计基于CD4细胞计数、血清转化后的时间、性别、年龄、传播类别和先前的治疗情况。
917名符合条件的受试者平均随访了3.4年，我们观察到139例事件。42.1%的参与者在研究期间接受了HAART。使用无协变量的Cox模型估计的率比为1.01（95%置信区间[CI]，0.68 - 1.49），使用具有随时间变化协变量的Cox模型估计的率比为0.90（95%CI，0.61 - 1.32）。MSM估计的因果率比为0.74（95%CI，0.49 - 1.12）。
MSM估计的HAART的有益效果在很大程度上被传统方法忽略了，这与先前随机研究的结果一致。MSM对随时间变化的协变量CD4细胞计数进行了适当调整，CD4细胞计数既是一个随时间变化的混杂因素，又受先前治疗的影响。
