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Parametric Potential-Outcome Survival Models for Causal Inference

机译:因果推断的参数潜在结果生存模型

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摘要

Estimating causal effects in clinical trials is often complicated by treatment noncompliance and missing outcomes. In time-to-event studies, estimation is further complicated by censoring. Censoring is a type of missing outcome, the mechanism of which may be non-ignorable. While new estimates have recently been proposed to account for noncompliance and missing outcomes, few studies have specifically considered time-to-event outcomes, where even the intention-to-treat (ITT) estimator is potentially biased for estimating causal effects of assigned treatment.In this thesis, we develop a series of parametric potential-outcome (PPO) survival models, for the analysis of randomised controlled trials (RCT) with time-to-event outcomes and noncompliance. Both ignorable and non-ignorable censoring mechanisms are considered. We approach model-fitting from a likelihood-based perspective, using the EM algorithm to locate maximum likelihood estimators. We are not aware of any previous work that addresses these complications jointly. In addition, we give new formulations for the average causal effect (ACE) and the complier average causal effect (CACE) to suit survival analysis. To illustrate the likelihood-based method proposed in this thesis, the HIP breast cancer trial data citep{Baker98, Shapiro88} were re-analysed using specific PPO-survival models, the Weibull and log-normal based PPO-survival models, which assume that the failure time and censored time distributions both follow Weibull or log-normal distributions. Furthermore, an extended PPO-survival model is also derived in this thesis, which permits investigation into the impact of causal effect after accommodating certain pre-treatment covariates. This is an important contribution to the potential outcomes, survival and RCT literature. For comparison, the Frangakis-Rubin (F-R) model citep{Frangakis99} is also applied to the HIP breast cancer trial data. To date, the F-R model has not yet been applied to any time-to-event data in the literature.
机译:由于治疗不依从和缺少结果,在临床试验中估计因果效应通常会变得很复杂。在事件研究中,审查会使得估计更加复杂。审查是缺少结果的一种,其机制可能是不可忽略的。尽管最近提出了新的估计数来说明不合规和缺少结果的情况,但很少有研究专门考虑事件发生时间,在这种情况下,即使是意向治疗(ITT)估计数也可能会因指定治疗的因果关系而产生偏差。在本文中,我们开发了一系列参数潜在结果(PPO)生存模型,用于分析具有事件发生时间和不依从情况的随机对照试验(RCT)。忽略了可忽略和不可忽略的检查机制。我们从基于似然的角度进行模型拟合,使用EM算法定位最大似然估计量。我们之前没有任何工作可以共同解决这些复杂性。此外,我们针对平均因果效应(ACE)和合规性平均因果效应(CACE)提供了新的公式,以适合生存分析。为了说明本文提出的基于可能性的方法,我们使用特定的PPO生存模型,基于Weibull和对数正态的PPO生存模型对HIP乳腺癌试验数据 citep {Baker98,Shapiro88}进行了重新分析。故障时间和删失时间分布均服从Weibull或对数正态分布。此外,本文还推导了扩展的PPO生存模型,该模型可以研究适应某些预处理协变量后因果关系的影响。这是对潜在结果,生存率和RCT文献的重要贡献。为了进行比较,Frangakis-Rubin(F-R)模型 citep {Frangakis99}也被应用于HIP乳腺癌试验数据。迄今为止,F-R模型尚未应用于文献中的任何事件时间数据。

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  • 作者

    Gong Zhaojing;

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  • 年度 2008
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