论文标题
一种新颖的估计，可以调整临床试验中的救援治疗
A novel estimand to adjust for rescue treatment in clinical trials
论文作者
论文摘要
随机临床试验结果的解释通常会因事件间事件而复杂。例如，除了随机治疗或代替其外，有时还会给患者提供救援药物，以应对患者的疾病恶化。这种药物的使用使对治疗分析的解释变得复杂。鉴于此，我们提出了一种新颖的估计，定义为如果有效手臂上的患者切换到救援药物，则只有在随机进行对照时才能切换时，就会观察到的意向性治疗效果。这使我们能够从救援药物对患者结局的影响中解散治疗效果，同时避免在推断出在缺乏救援药物的情况下推断出意图处理的效果时通常需要的强大外推。我们开发了一种反概率加权方法，以在特定的不可测试的假设下估计这一估计值，鉴于该假设，我们提出了灵敏度分析。我们使用该方法来分析Janssen Pharmaceuticals进行的临床试验，其中长期患者可以出于道德原因改用救助药物。蒙特卡洛模拟证实，所提出的估计量在中等样本中是公正的。
The interpretation of randomised clinical trial results is often complicated by intercurrent events. For instance, rescue medication is sometimes given to patients in response to worsening of their disease, either in addition to the randomised treatment or in its place. The use of such medication complicates the interpretation of the intention-to-treat analysis. In view of this, we propose a novel estimand defined as the intention-to-treat effect that would have been observed, had patients on the active arm been switched to rescue medication if and only if they would have been switched when randomised to control. This enables us to disentangle the treatment effect from the effect of rescue medication on a patient's outcome, while avoiding the strong extrapolations that are typically needed when inferring what the intention-to-treat effect would have been in the absence of rescue medication. We develop an inverse probability weighting method to estimate this estimand under specific untestable assumptions, in view of which we propose a sensitivity analysis. We use the method for the analysis of a clinical trial conducted by Janssen Pharmaceuticals, in which chronically ill patients can switch to rescue medication for ethical reasons. Monte Carlo simulations confirm that the proposed estimator is unbiased in moderate sample sizes.
