论文标题

半参数灵敏度分析,用于不规则和信息性评估时间的试验

Semi-Parametric Sensitivity Analysis for Trials with Irregular and Informative Assessment Times

论文作者

Smith, Bonnie B., Gao, Yujing, Yang, Shu, Varadhan, Ravi, Apter, Andrea J., Scharfstein, Daniel O.

论文摘要

许多试验旨在在随机分组后或预先指定的时间内收集结果。如果实际上评估参与者的时间存在可变性,这可能会对学习治疗的效果构成挑战,因为并非所有参与者都在感兴趣的时期进行结果评估。此外,在给定时间,观察到的结果值可能不能代表所有参与者的结果。已经开发了一种方法,可以说明某些类型的不规则和信息丰富的评估时间;但是,由于这些方法依赖于无法测试的假设,因此需要进行灵敏度分析。我们开发了一种通过可解释的评估者(EA)假设进行基准测试的方法,根据该假设,每次评估和结果仅通过在此时间之前收集的数据相关。我们的方法使用一个指数倾斜假设,该假设受灵敏度分析参数的控制,该假设与EA假设偏离。我们的推论策略基于新的基于影响功能的新,增强的反向强度加权估计器。我们的方法允许对观察到的数据进行灵活的半参数建模,该模型与灵敏度参数的规范分开。我们将方法应用于具有不受控制哮喘的低收入个体的随机试验,并详细说明了我们的估计程序的实施。

Many trials are designed to collect outcomes at or around pre-specified times after randomization. If there is variability in the times when participants are actually assessed, this can pose a challenge to learning the effect of treatment, since not all participants have outcome assessments at the times of interest. Furthermore, observed outcome values may not be representative of all participants' outcomes at a given time. Methods have been developed that account for some types of such irregular and informative assessment times; however, since these methods rely on untestable assumptions, sensitivity analyses are needed. We develop a methodology that is benchmarked at the explainable assessmen (EA) assumption, under which assessment and outcomes at each time are related only through data collected prior to that time. Our method uses an exponential tilting assumption, governed by a sensitivity analysis parameter, that posits deviations from the EA assumption. Our inferential strategy is based on a new influence function-based, augmented inverse intensity-weighted estimator. Our approach allows for flexible semiparametric modeling of the observed data, which is separated from specification of the sensitivity parameter. We apply our method to a randomized trial of low-income individuals with uncontrolled asthma, and we illustrate implementation of our estimation procedure in detail.

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