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Highly robust causal semiparametric U-statistic with applications in biomedical studies

Abstract With our increased ability to capture large data, causal inference has received renewed attention and is playing an ever-important role in biomedicine and economics. However, one major methodological hurdle is that existing methods rely on many unverifiable model assumptions. Thus robust modeling is a critically important approach complementary to sensitivity analysis, where it compares results under various model assumptions. The more robust a method is with respect to model assumptions, the more worthy it is. The doubly robust estimator (DRE) is a significant advance in this direction. However, in practice, many outcome measures are functionals of multiple distributions, and so are the associated estimands, which can only be estimated via U-statistics. Thus most existing DREs do not apply. This article proposes a broad class of highly robust U-statistic estimators (HREs), which use semiparametric specifications for both the propensity score and outcome models in constructing the U-statistic. Thus, the HRE is more robust than the existing DREs. We derive comprehensive asymptotic properties of the proposed estimators and perform extensive simulation studies to evaluate their finite sample performance and compare them with the corresponding parametric U-statistics and the naive estimators, which show significant advantages. Then we apply the method to analyze a clinical trial from the AIDS Clinical Trials Group.