论文标题

生殖医学RCT中结果截断的含义:试验者和模拟研究的模拟平台

The implications of outcome truncation in reproductive medicine RCTs: a simulation platform for trialists and simulation study

论文作者

Wilkinson, Jack, Huang, Jonathan, Marsden, Antonia, Harhay, Michael, Vail, Andy, Roberts, Stephen A

论文摘要

生殖医学中的随机对照试验通常受到结果截断,在研究结果仅在参与者的一部分中定义。例子包括出生体重(仅在分娩的参与者子组中可测量)和流产(只能在怀孕的参与者中发生)。通常通过比较子组中的治疗臂(比较了育生的亚组中的出生体重,或者在怀孕的亚组中的流产)来分析这些。但是,当治疗影响观察到的概率(即生存)时,这种方法并不代表随机比较。这对生殖试验的实际含义尚不清楚。我们开发了一个模拟平台,以研究结果截断对生殖医学试验的含义。我们使用它进行了仿真研究,其中我们考虑了截断的连续和二元结果的标准统计分析的偏差,类型1误差,覆盖率和精度。对中间变量的治疗效果的增加,中间和结果变量之间的混淆强度以及治疗与混杂因素之间的相互作用会对性能产生不利影响。但是,在参数范围内,我们认为更现实,不利影响通常并不剧烈。对于二元结果,该研究强调,结果截断可能不会导致研究部门的参与者经历结果事件。发现这对推论产生了严重的后果,这可能对荟萃分析产生影响。

Randomised controlled trials in reproductive medicine are often subject to outcome truncation, where study outcomes are only defined in a subset of participants. Examples include birthweight (measurable only in the subgroup of participants who give birth) and miscarriage (which can only occur in participants who become pregnant). These are typically analysed by making a comparison between treatment arms within the subgroup (comparing birthweights in the subgroup who gave birth, or miscarriages in the subgroup who became pregnant). However, this approach does not represent a randomised comparison when treatment influences the probability of being observed (i.e. survival). The practical implications of this for reproductive trials are unclear. We developed a simulation platform to investigate the implications of outcome truncation for reproductive medicine trials. We used this to perform a simulation study, in which we considered the bias, Type 1 error, coverage, and precision of standard statistical analyses for truncated continuous and binary outcomes. Increasing treatment effect on the intermediate variable, strength of confounding between the intermediate and outcome variables, and interactions between treatment and confounder were found to adversely affect performance. However, within parameter ranges we would consider to be more realistic, the adverse effects were generally not drastic. For binary outcomes, the study highlighted that outcome truncation may lead to none of the participants in a study arm experiencing the outcome event. This was found to have severe consequences for inferences, and this may have implications for meta-analysis.

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