The Use of a Variable Representing Compliance Improves Accuracy of Estimation of the Effect of Treatment Allocation Regardless of Discontinuation in Trials with Incomplete Follow-up
The Use of a Variable Representing Compliance Improves Accuracy of Estimation of the Effect of Treatment Allocation Regardless of Discontinuation in Trials with Incomplete Follow-up
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DOI：
10.1080/19466315.2020.1736141
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发表时间：
2020-04-17
影响因子：
1.8
通讯作者：
Gallo, Ciro
中科院分区：
文献类型：
--
作者：
Guizzaro, Lorenzo;Petavy, Frank;Gallo, Ciro
-在临床试验中，并非所有随机分组的患者都遵循分配给他们的治疗过程。人们越来越认识到这种偏差的潜在影响，这也是 ICH E9 附录草案中重新定义估计目标（“估计量”）的原因之一。其中，无论遵守情况如何，治疗分配的效果似乎是实际利益的估计值，符合意向治疗原则。本研究旨在评估实施“治疗策略”策略时，停药后随访不完整的试验中不同估计技术的表现。为了实现这一目标，我们（i）将合理的数据生成模型建模并可视化为有向无环图； (ii) 调查哪组变量可以识别和估计这种影响； (iii) 模拟了 10,000 项重度抑郁症试验，其真实治疗效果、停止治疗的患者比例以及不完整的随访情况各不相同。我们的结果表明，至少在“随机缺失”设置中，所有研究的估计方法在使用代表合规性的变量时都会提高其性能。停药后随访的比例越高，这种效果越明显。
-In Clinical Trials, not all randomized patients follow the course of treatment they are allocated to. The potential impact of such deviations is increasingly recognized, and it has been one of the reasons for a redefinition of the targets of estimation ("Estimands") in the ICH E9 draft Addendum. Among others, the effect of treatment assignment, regardless of the adherence, appears an Estimand of practical interest, in line with the intention-to-treat principle. This study aims at evaluating the performance of different estimation techniques in trials with incomplete post-discontinuation follow-up when a "treatment-policy" strategy is implemented. To achieve that, we have (i) modeled and visualized as directed acyclic diagram a reasonable data-generating model; (ii) investigated which set of variables allows identification and estimation of such effect; (iii) simulated 10,000 trials in Major Depressive Disorder, with varying real treatment effects, proportions of patients discontinuing the treatment, and incomplete follow-up. Our results suggest that, at least in a "Missing at Random" setting, all studied estimation methods increase their performance when a variable representing compliance is used. This effect is more pronounced the higher the proportion of post-discontinuation follow-up is.