Finite Sample Inference for Targeted Learning

The Highly-Adaptive-Lasso(HAL)-TMLE is an efficient estimator of a pathwise differentiable parameter in a statistical model that at minimal (and possibly only) assumes that the sectional variation norm of the true nuisance parameters are finite. It relies on an initial estimator (HAL-MLE) of the nuisance parameters by minimizing the empirical risk over the parameter space under the constraint that sectional variation norm is bounded by a constant, where this constant can be selected with cross-validation. In the formulation of the HALMLE this sectional variation norm corresponds with the sum of absolute value of coefficients for an indicator basis. Due to its reliance on machine learning, statistical inference for the TMLE has been based on its normal limit distribution, thereby potentially ignoring a large second order remainder in finite samples. In this article, we present four methods for construction of a finite sample 0.95-confidence interval that use the nonparametric bootstrap to estimate the finite sample distribution of the HAL-TMLE or a conservative distribution dominating the true finite sample distribution. We prove that it consistently estimates the optimal normal limit distribution, while its approximation error is driven by the performance of the bootstrap for a well behaved empirical process. We demonstrate our general inferential methods for 1) nonparametric estimation of the average treatment effect based on observing on each unit a covariate vector, binary treatment, and outcome, and for 2) nonparametric estimation of the integral of the square of the multivariate density of the data distribution.