Structural cumulative survival models for estimation of treatment effects accounting for treatment switching in randomized experiments.
Structural cumulative survival models for estimation of treatment effects accounting for treatment switching in randomized experiments.
复制标题
用于估计随机实验中治疗切换的治疗效果的结构累积生存模型。
DOI：
10.1111/biom.13704
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发表时间：
2023
期刊：
影响因子：
1.9
通讯作者：
Tchetgen,EricJTchetgen
中科院分区：
文献类型：
--
作者：
Ying,Andrew;Tchetgen,EricJTchetgen
在随机对照试验中，当一个治疗组的患者在随访期间转换到另一个治疗组时，发生治疗转换。这可以发生在疾病进展的时候，由此可以向对照组中的患者提供实验性治疗。众所周知，未能解释治疗转换可能会严重偏倚估计的治疗因果效应。在本文中，我们的目的是解释治疗转换的潜在影响，在重新分析中评价核苷逆转录酶抑制剂（NRTIs）对接受新的抗逆转录病毒治疗方案的受试者的安全性结局（至首次严重或更严重体征或症状的时间）的治疗效果，该方案在包括或省略NRTIs的优化治疗试验中包括或省略NRTIs。我们提出了一个估计的治疗因果效应的截尾时间事件的结果下，结构累积生存模型，利用随机化作为一个工具变量来考虑选择性治疗转换。我们建立了所提出的估计是一致一致的和渐近高斯的，具有一致的方差估计和置信区间，其有限样本性能通过广泛的模拟来评估。实现所有建议方法的R包'ivsacim'在R CRAN上免费提供。结果表明，在新的优化治疗方案中添加NRTI与省略NRTI相比，可能会增加安全性结局的风险。
Treatment switching in a randomized controlled trial occurs when a patient in one treatment arm switches to another arm during follow‐up. This can occur at the point of disease progression, whereby patients in the control arm may be offered the experimental treatment. It is widely known that failure to account for treatment switching can seriously bias the estimated treatment causal effect. In this paper, we aim to account for the potential impact of treatment switching in a reanalysis evaluating the treatment effect of nucleoside reverse transcriptase inhibitors (NRTIs) on a safety outcome (time to first severe or worse sign or symptom) in participants receiving a new antiretroviral regimen that either included or omitted NRTIs in the optimized treatment that includes or omits NRTIs trial. We propose an estimator of a treatment causal effect for a censored time to event outcome under a structural cumulative survival model that leverages randomization as an instrumental variable to account for selective treatment switching. We establish that the proposed estimator is uniformly consistent and asymptotically Gaussian, with a consistent variance estimator and confidence intervals given, whose finite‐sample performance is evaluated via extensive simulations. An R package ‘ivsacim’ implementing all proposed methods is freely available on R CRAN. Results indicate that adding NRTIs versus omitting NRTIs to a new optimized treatment regime may increase the risk for a safety outcome.