This paper considers one-step targeted maximum likelihood estimation method for general competing risks and survival analysis settings where event times take place on the positive real line R+ and are subject to right-censoring. Our interest is overa
ll in the effects of baseline treatment decisions, static, dynamic or stochastic, possibly confounded by pre-treatment covariates. We point out two overall contributions of our work. First, our method can be used to obtain simultaneous inference across all absolute risks in competing risks settings. Second, we present a practical result for achieving inference for the full survival curve, or a full absolute risk curve, across time by targeting over a fine enough grid of points. The one-step procedure is based on a one-dimensional universal least favorable submodel for each cause-specific hazard that can be implemented in recursive steps along a corresponding universal least favorable submodel. We present a theorem for conditions to achieve weak convergence of the estimator for an infinite-dimensional target parameter. Our empirical study demonstrates the use of the methods.
This paper studies the generalization of the targeted minimum loss-based estimation (TMLE) framework to estimation of effects of time-varying interventions in settings where both interventions, covariates, and outcome can happen at subject-specific t
ime-points on an arbitrarily fine time-scale. TMLE is a general template for constructing asymptotically linear substitution estimators for smooth low-dimensional parameters in infinite-dimensional models. Existing longitudinal TMLE methods are developed for data where observations are made on a discrete time-grid. We consider a continuous-time counting process model where intensity measures track the monitoring of subjects, and focus on a low-dimensional target parameter defined as the intervention-specific mean outcome at the end of follow-up. To construct our TMLE algorithm for the given statistical estimation problem we derive an expression for the efficient influence curve and represent the target parameter as a functional of intensities and conditional expectations. The high-dimensional nuisance parameters of our model are estimated and updated in an iterative manner according to separate targeting steps for the involved intensities and conditional expectations. The resulting estimator solves the efficient influence curve equation. We state a general efficiency theorem and describe a highly adaptive lasso estimator for nuisance parameters that allows us to establish asymptotic linearity and efficiency of our estimator under minimal conditions on the underlying statistical model.
The covariance matrix plays a fundamental role in many modern exploratory and inferential statistical procedures, including dimensionality reduction, hypothesis testing, and regression. In low-dimensional regimes, where the number of observations far
exceeds the number of variables, the optimality of the sample covariance matrix as an estimator of this parameter is well-established. High-dimensional regimes do not admit such a convenience, however. As such, a variety of estimators have been derived to overcome the shortcomings of the sample covariance matrix in these settings. Yet, the question of selecting an optimal estimator from among the plethora available remains largely unaddressed. Using the framework of cross-validated loss-based estimation, we develop the theoretical underpinnings of just such an estimator selection procedure. In particular, we propose a general class of loss functions for covariance matrix estimation and establish finite-sample risk bounds and conditions for the asymptotic optimality of the cross-validated estimator selector with respect to these loss functions. We evaluate our proposed approach via a comprehensive set of simulation experiments and demonstrate its practical benefits by application in the exploratory analysis of two single-cell transcriptome sequencing datasets. A free and open-source software implementation of the proposed methodology, the cvCovEst R package, is briefly introduced.
The current work is motivated by the need for robust statistical methods for precision medicine; as such, we address the need for statistical methods that provide actionable inference for a single unit at any point in time. We aim to learn an optimal
, unknown choice of the controlled components of the design in order to optimize the expected outcome; with that, we adapt the randomization mechanism for future time-point experiments based on the data collected on the individual over time. Our results demonstrate that one can learn the optimal rule based on a single sample, and thereby adjust the design at any point t with valid inference for the mean target parameter. This work provides several contributions to the field of statistical precision medicine. First, we define a general class of averages of conditional causal parameters defined by the current context for the single unit time-series data. We define a nonparametric model for the probability distribution of the time-series under few assumptions, and aim to fully utilize the sequential randomization in the estimation procedure via the double robust structure of the efficient influence curve of the proposed target parameter. We present multiple exploration-exploitation strategies for assigning treatment, and methods for estimating the optimal rule. Lastly, we present the study of the data-adaptive inference on the mean under the optimal treatment rule, where the target parameter adapts over time in response to the observed context of the individual. Our target parameter is pathwise differentiable with an efficient influence function that is doubly robust - which makes it easier to estimate than previously proposed variations. We characterize the limit distribution of our estimator under a Donsker condition expressed in terms of a notion of bracketing entropy adapted to martingale settings.
Causal mediation analysis has historically been limited in two important ways: (i) a focus has traditionally been placed on binary treatments and static interventions, and (ii) direct and indirect effect decompositions have been pursued that are only
identifiable in the absence of intermediate confounders affected by treatment. We present a theoretical study of an (in)direct effect decomposition of the population intervention effect, defined by stochastic interventions jointly applied to the treatment and mediators. In contrast to existing proposals, our causal effects can be evaluated regardless of whether a treatment is categorical or continuous and remain well-defined even in the presence of intermediate confounders affected by treatment. Our (in)direct effects are identifiable without a restrictive assumption on cross-world counterfactual independencies, allowing for substantive conclusions drawn from them to be validated in randomized controlled trials. Beyond the novel effects introduced, we provide a careful study of nonparametric efficiency theory relevant for the construction of flexible, multiply robust estimators of our (in)direct effects, while avoiding undue restrictions induced by assuming parametric models of nuisance parameter functionals. To complement our nonparametric estimation strategy, we introduce inferential techniques for constructing confidence intervals and hypothesis tests, and discuss open source software implementing the proposed methodology.
We study the stochastic convergence of the Ces`{a}ro mean of a sequence of random variables. These arise naturally in statistical problems that have a sequential component, where the sequence of random variables is typically derived from a sequence o
f estimators computed on data. We show that establishing a rate of convergence in probability for a sequence is not sufficient in general to establish a rate in probability for its Ces`{a}ro mean. We also present several sets of conditions on the sequence of random variables that are sufficient to guarantee a rate of convergence for its Ces`{a}ro mean. We identify common settings in which these sets of conditions hold.
Unlike the commonly used parametric regression models such as mixed models, that can easily violate the required statistical assumptions and result in invalid statistical inference, target maximum likelihood estimation allows more realistic data-gene
rative models and provides double-robust, semi-parametric and efficient estimators. Target maximum likelihood estimators (TMLEs) for the causal effect of a community-level static exposure were previously proposed by Balzer et al. In this manuscript, we build on this work and present identifiability results and develop two semi-parametric efficient TMLEs for the estimation of the causal effect of the single time-point community-level stochastic intervention whose assignment mechanism can depend on measured and unmeasured environmental factors and its individual-level covariates. The first community-level TMLE is developed under a general hierarchical non-parametric structural equation model, which can incorporate pooled individual-level regressions for estimating the outcome mechanism. The second individual-level TMLE is developed under a restricted hierarchical model in which the additional assumption of no covariate interference within communities holds. The proposed TMLEs have several crucial advantages. First, both TMLEs can make use of individual level data in the hierarchical setting, and potentially reduce finite sample bias and improve estimator efficiency. Second, the stochastic intervention framework provides a natural way for defining and estimating casual effects where the exposure variables are continuous or discrete with multiple levels, or even cannot be directly intervened on. Also, the positivity assumption needed for our proposed causal parameters can be weaker than the version of positivity required for other casual parameters.
Over the past years, many applications aim to assess the causal effect of treatments assigned at the community level, while data are still collected at the individual level among individuals of the community. In many cases, one wants to evaluate the
effect of a stochastic intervention on the community, where all communities in the target population receive probabilistically assigned treatments based on a known specified mechanism (e.g., implementing a community-level intervention policy that target stochastic changes in the behavior of a target population of communities). The tmleCommunity package is recently developed to implement targeted minimum loss-based estimation (TMLE) of the effect of community-level intervention(s) at a single time point on an individual-based outcome of interest, including the average causal effect. Implementations of the inverse-probability-of-treatment-weighting (IPTW) and the G-computation formula (GCOMP) are also available. The package supports multivariate arbitrary (i.e., static, dynamic or stochastic) interventions with a binary or continuous outcome. Besides, it allows user-specified data-adaptive machine learning algorithms through SuperLearner, sl3 and h2oEnsemble packages. The usage of the tmleCommunity package, along with a few examples, will be described in this paper.
We consider the model selection task in the stochastic contextual bandit setting. Suppose we are given a collection of base contextual bandit algorithms. We provide a master algorithm that combines them and achieves the same performance, up to consta
nts, as the best base algorithm would, if it had been run on its own. Our approach only requires that each algorithm satisfy a high probability regret bound. Our procedure is very simple and essentially does the following: for a well chosen sequence of probabilities $(p_{t})_{tgeq 1}$, at each round $t$, it either chooses at random which candidate to follow (with probability $p_{t}$) or compares, at the same internal sample size for each candidate, the cumulative reward of each, and selects the one that wins the comparison (with probability $1-p_{t}$). To the best of our knowledge, our proposal is the first one to be rate-adaptive for a collection of general black-box contextual bandit algorithms: it achieves the same regret rate as the best candidate. We demonstrate the effectiveness of our method with simulation studies.
Inverse probability weighted estimators are the oldest and potentially most commonly used class of procedures for the estimation of causal effects. By adjusting for selection biases via a weighting mechanism, these procedures estimate an effect of in
terest by constructing a pseudo-population in which selection biases are eliminated. Despite their ease of use, these estimators require the correct specification of a model for the weighting mechanism, are known to be inefficient, and suffer from the curse of dimensionality. We propose a class of nonparametric inverse probability weighted estimators in which the weighting mechanism is estimated via undersmoothing of the highly adaptive lasso, a nonparametric regression function proven to converge at $n^{-1/3}$-rate to the true weighting mechanism. We demonstrate that our estimators are asymptotically linear with variance converging to the nonparametric efficiency bound. Unlike doubly robust estimators, our procedures require neither derivation of the efficient influence function nor specification of the conditional outcome model. Our theoretical developments have broad implications for the construction of efficient inverse probability weighted estimators in large statistical models and a variety of problem settings. We assess the practical performance of our estimators in simulation studies and demonstrate use of our proposed methodology with data from a large-scale epidemiologic study.
