Title: Causal interpretation of the sibling comparison and its relation to the cross-over design Show Chinese title

Title: 因果解释的兄弟比较及其与交叉设计的关系

Abstract: The intuitive motivation for employing a sibling comparison design is to adjust for confounding that is constant within families. Such confounding can be caused by variables that otherwise might prove difficult to measure, for example factors relating to genetics, environment, and upbringing. Recent methodological investigations have shown that despite its intuitive appeal, the conventionally employed analysis does not relate to a well-defined causal target, even in the case of constant confounding. A main challenge is that the analysis will target the subpopulation of exposure discordant pairs. In the presence of an effect of the cosibling's exposure on the sibling's outcome, there is a second challenge, namely that the effect corresponds to an intervention that always exposes the cosibling to the opposite exposure from the sibling. We characterise the sibling comparison in terms of the cross-over design. Estimands of interest are discussed before using this characterisation to establish more natural conditions for targeting an appropriate causal parameter. We cast the above-mentioned challenges of the sibling comparison in terms of those facing the cross-over trialist: in order to target an appropriate estimand one must be able to argue the absence of a certain type of carry-over effect as well as absence of trial-by-treatment interaction, thus establishing that the former study design emulates the latter warts and all. We explore weighting to counter the effects of such interactions and to target other estimands. The weights rely on estimates of the unobserved confounding structure. Through simulations and an example analysis, we illustrate its potential usefulness to assess the validity of the assumptions of the matched analysis. We briefly discuss an extension of the weighting procedure to remove selection bias based on data from a population-level reference sample. Show Chinese abstract

Abstract: 采用兄弟比较设计的直观动机是为了调整家庭内部恒定的混杂因素。 这种混杂可能由其他情况下可能难以测量的变量引起，例如与遗传、环境和抚养有关的因素。 最近的方法论研究显示，尽管这种设计具有直观吸引力，但传统使用的分析方法即使在恒定混杂的情况下，也不对应于一个明确的因果目标。 主要挑战在于，该分析将针对暴露不一致对的子种群。 在共同胞的暴露对同胞结果有影响的情况下，还有一个挑战，即该影响对应于一种干预，该干预总是使共同胞暴露于与同胞相反的暴露。 我们用交叉设计来描述兄弟比较。 在使用这种描述来建立针对适当因果参数的更自然条件之前，讨论了感兴趣的估计量。 我们将上述兄弟比较的挑战以交叉试验者所面临的挑战来表述：为了针对适当的估计量，必须能够论证某种类型的残留效应的缺失以及试验与治疗交互作用的缺失，从而确立前者研究设计在各方面都模拟后者。 我们探讨了加权方法来抵消这些交互作用的影响并针对其他估计量。 权重依赖于对未观察到的混杂结构的估计。 通过模拟和一个示例分析，我们说明了其潜在的有用性，以评估匹配分析假设的有效性。 我们简要讨论了将加权过程扩展到消除选择偏差的方法，该方法基于来自总体参考样本的数据。