Treatment switching frequently occurs in clinical trials due to ethical reasons. Intent-to-treat analysis without adjusting for switching yields biased and inefficient estimates of the treatment effects. In this paper, we propose a class of semiparametric semi-competing risks transition survival models to accommodate two-way time-varying switching. Theoretical properties of the proposed method are examined. An efficient expectation–maximization algorithm is derived to obtain maximum likelihood estimates and model diagnostic tools. Existing software is used to implement the algorithm. Simulation studies are conducted to demonstrate the validity of the model. The proposed method is further applied to data from a clinical trial with patients having recurrent or metastatic squamous-cell carcinoma of head and neck.

中文翻译：

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使用双向时变治疗切换估计治疗效果和模型诊断：在头颈部研究中的应用。

由于伦理原因，治疗转换经常发生在临床试验中。未调整转换的意向治疗分析产生了对治疗效果的偏倚和低效估计。在本文中，我们提出了一类半参数半竞争风险转移生存模型，以适应双向时变切换。对所提出方法的理论特性进行了检验。一个有效的期望最大化算法被推导出来获得最大似然估计和模型诊断工具。现有软件用于实现该算法。进行模拟研究以证明模型的有效性。所提出的方法进一步应用于来自患有复发性或转移性头颈部鳞状细胞癌患者的临床试验的数据。