STATISTICAL INFERENCE FOR THE MEAN OUTCOME UNDER A POSSIBLY NON-UNIQUE OPTIMAL TREATMENT STRATEGY.

We consider challenges that arise in the estimation of the mean outcome under an optimal individualized treatment strategy defined as the treatment rule that maximizes the population mean outcome, where the candidate treatment rules are restricted to depend on baseline covariates. We prove a necessary and sufficient condition for the pathwise differentiability of the optimal value, a key condition needed to develop a regular and asymptotically linear (RAL) estimator of the optimal value. The stated condition is slightly more general than the previous condition implied in the literature. We then describe an approach to obtain root-n rate confidence intervals for the optimal value even when the parameter is not pathwise differentiable. We provide conditions under which our estimator is RAL and asymptotically efficient when the mean outcome is pathwise differentiable. We also outline an extension of our approach to a multiple time point problem. All of our results are supported by simulations.

Parametric-rate inference for one-sided differentiable parameters.

Suppose one has a collection of parameters indexed by a (possibly infinite dimensional) set. Given data generated from some distribution, the objective is to estimate the maximal parameter in this collection evaluated at the distribution that generated the data. This estimation problem is typically non-regular when the maximizing parameter is non-unique, and as a result standard asymptotic techniques generally fail in this case. We present a technique for developing parametric-rate confidence intervals for the quantity of interest in these non-regular settings. We show that our estimator is asymptotically efficient when the maximizing parameter is unique so that regular estimation is possible. We apply our technique to a recent example from the literature in which one wishes to report the maximal absolute correlation between a prespecified outcome and one of p predictors. The simplicity of our technique enables an analysis of the previously open case where p grows with sample size. Specifically, we only require that log p grows slower than n , where n is the sample size. We show that, unlike earlier approaches, our method scales to massive data sets: the point estimate and confidence intervals can be constructed in O(np) time.

Evaluating the impact of treating the optimal subgroup.

Suppose we have a binary treatment used to influence an outcome. Given data from an observational or controlled study, we wish to determine whether or not there exists some subset of observed covariates in which the treatment is more effective than the standard practice of no treatment. Furthermore, we wish to quantify the improvement in population mean outcome that will be seen if this subgroup receives treatment and the rest of the population remains untreated. We show that this problem is surprisingly challenging given how often it is an (at least implicit) study objective. Blindly applying standard techniques fails to yield any apparent asymptotic results, while using existing techniques to confront the non-regularity does not necessarily help at distributions where there is no treatment effect. Here, we describe an approach to estimate the impact of treating the subgroup which benefits from treatment that is valid in a nonparametric model and is able to deal with the case where there is no treatment effect. The approach is a slight modification of an approach that recently appeared in the individualized medicine literature.