Analyses of biomedical studies often necessitate modeling longitudinal causal effects. The current focus on personalized medicine and effect heterogeneity makes this task even more challenging. Towards this end, structural nested mean models (SNMMs) are fundamental tools for studying heterogeneous treatment effects in longitudinal studies. However, when outcomes are binary, current methods for estimating multiplicative and additive SNMM parameters suffer from variation dependence between the causal parameters and the non-causal nuisance parameters. This leads to a series of difficulties in interpretation, estimation and computation. These difficulties have hindered the uptake of SNMMs in biomedical practice, where binary outcomes are very common. We solve the variation dependence problem for the binary multiplicative SNMM via a reparametrization of the non-causal nuisance parameters. Our novel nuisance parameters are variation independent of the causal parameters, and hence allow for coherent modeling of heterogeneous effects from longitudinal studies with binary outcomes. Our parametrization also provides a key building block for flexible doubly robust estimation of the causal parameters. Along the way, we prove that an additive SNMM with binary outcomes does not admit a variation independent parametrization, thereby justifying the restriction to multiplicative SNMMs.
翻译:生物医学研究的分析往往需要模拟纵向因果关系效应。目前对个性化医学和效应异质性的侧重,使得这项任务更具挑战性。为此,结构性嵌套平均模型(SNMMs)是研究纵向研究中不同治疗效应的基本工具。然而,当结果为二进制时,目前用于估算多复制性和添加性SNMM参数的方法取决于因果参数和非因果干扰参数之间的差异性依赖性。这导致一系列解释、估计和计算方面的困难。这些困难阻碍了生物医学实践对SNMMMS的采用,因为二进制结果非常常见。我们通过非因果骚扰参数的再平衡解决SNMMM的变异依赖性问题。我们新的微调参数是因果参数的互异性,因此可以对具有二进制结果的长性研究所产生的混杂效应进行连贯的建构。我们的配方还提供了一个关键建筑块,可以灵活地对因果参数进行可靠的估算。与此同时,我们证明,通过非因果性骚扰性刺激性调整的SNMMMM(S)的多复制结果是独立的。