Emulating a trial of joint dynamic strategies: An application to monitoring and treatment of HIV-positive individuals
Emulating a trial of joint dynamic strategies: An application to monitoring and treatment of HIV-positive individuals
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DOI：
10.1002/sim.8120
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发表时间：
2019-06-15
影响因子：
2
通讯作者：
Hernan, Miguel A.
中科院分区：
文献类型：
--
作者：
Caniglia, Ellen C.;Robins, James M.;Hernan, Miguel A.
关于何时开始或转换治疗的决定通常取决于对个体进行监测或测试的频率。例如，转换抗逆转录病毒疗法的最佳时间取决于 HIV 阳性个体检测 HIV RNA 的频率。本文描述了一种使用观察数据来比较联合监测和治疗策略的方法，并将该方法应用于艾滋病毒研究中的临床相关问题：何时可以降低监测频率以及个体何时应从一线治疗方案切换到新方案？我们概述了目标试验，该试验将比较感兴趣的动态策略，然后描述如何使用来自 HIV-因果合作和艾滋病研究中心综合临床系统网络中的艾滋病毒阳性个体的数据来模拟它。正如我们的例子所示，当很少有人在长期的随访中遵循动态的兴趣策略时，我们描述了如何利用一个额外的假设：监控对兴趣结果没有直接影响。我们比较了有和没有“无直接影响”假设的结果。我们发现，与500个细胞/μl的CD4阈值相比，监测频率在350个细胞/μl的阈值下降低，以及在1000个拷贝/ml的HIV-RNA阈值与200个拷贝/ml的HIV-RNA阈值下切换治疗的策略之间的生存率和无艾滋病生存率几乎没有差异。 “无直接影响”假设导致风险差异估计的效率提高，有效样本量增加了 7 至 53 倍。
Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV-positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first-line treatment regimen to a new regimen? We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV-positive individuals included in the HIV-CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow-up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the "no direct effect" assumption. We found little differences on survival and AIDS-free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/mu l compared with 500 cells/mu l and where treatment was switched at an HIV-RNA threshold of 1000 copies/ml compared with 200 copies/ml. The "no direct effect" assumption resulted in efficiency improvements for the risk difference estimates ranging from an 7- to 53-fold increase in the effective sample size.