In survival contexts, substantial literature exists on estimating optimal treatment regimes, where treatments are assigned based on personal characteristics for the purpose of maximizing the survival probability. These methods assume that a set of covariates is sufficient to deconfound the treatment-outcome relationship. Nevertheless, the assumption can be limiting in observational studies or randomized trials in which noncompliance occurs. Thus, we advance a novel approach for estimating the optimal treatment regime when certain confounders are not observable and a binary instrumental variable is available. Specifically, via a binary instrumental variable, we propose two semiparametric estimators for the optimal treatment regime, one of which possesses the desirable property of double robustness, by maximizing Kaplan-Meier-like estimators within a pre-defined class of regimes. Because the Kaplan-Meier-like estimators are jagged, we incorporate kernel smoothing methods to enhance their performance. Under appropriate regularity conditions, the asymptotic properties are rigorously established. Furthermore, the finite sample performance is assessed through simulation studies. We exemplify our method using data from the National Cancer Institute's (NCI) prostate, lung, colorectal, and ovarian cancer screening trial.
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The Work Disability Functional Assessment Battery (WD-FAB) is a multidimensional item response theory (IRT) instrument designed for assessing work-related mental and physical function based on responses to an item bank. In prior iterations it was developed using traditional means -- linear factorization and null hypothesis statistical testing for item partitioning/selection, and finally, posthoc calibration of disjoint unidimensional IRT models. As a result, the WD-FAB, like many other IRT instruments, is a posthoc model. Its item partitioning, based on exploratory factor analysis, is blind to the final nonlinear IRT model and is not performed in a manner consistent with goodness of fit to the final model. In this manuscript, we develop a Bayesian hierarchical model for self-consistently performing the following simultaneous tasks: scale factorization, item selection, parameter identification, and response scoring. This method uses sparsity-based shrinkage to obviate the linear factorization and null hypothesis statistical tests that are usually required for developing multidimensional IRT models, so that item partitioning is consistent with the ultimate nonlinear factor model. We also analogize our multidimensional IRT model to probabilistic autoencoders, specifying an encoder function that amortizes the inference of ability parameters from item responses. The encoder function is equivalent to the "VBE" step in a stochastic variational Bayesian expectation maximization (VBEM) procedure that we use for approxiamte Bayesian inference on the entire model. We use the method on a sample of WD-FAB item responses and compare the resulting item discriminations to those obtained using the traditional posthoc method.
Auctions are modeled as Bayesian games with continuous type and action spaces. Determining equilibria in auction games is computationally hard in general and no exact solution theory is known. We introduce an algorithmic framework in which we discretize type and action space and then learn distributional strategies via online optimization algorithms. One advantage of distributional strategies is that we do not have to make any assumptions on the shape of the bid function. Besides, the expected utility of agents is linear in the strategies. It follows that if our optimization algorithms converge to a pure strategy, then they converge to an approximate equilibrium of the discretized game with high precision. Importantly, we show that the equilibrium of the discretized game approximates an equilibrium in the continuous game. In a wide variety of auction games, we provide empirical evidence that the approach approximates the analytical (pure) Bayes Nash equilibrium closely. This speed and precision is remarkable, because in many finite games learning dynamics do not converge or are even chaotic. In standard models where agents are symmetric, we find equilibrium in seconds. While we focus on dual averaging, we show that the overall approach converges independent of the regularizer and alternative online convex optimization methods achieve similar results, even though the discretized game neither satisfies monotonicity nor variational stability globally. The method allows for interdependent valuations and different types of utility functions and provides a foundation for broadly applicable equilibrium solvers that can push the boundaries of equilibrium analysis in auction markets and beyond.
Statistical models typically capture uncertainties in our knowledge of the corresponding real-world processes, however, it is less common for this uncertainty specification to capture uncertainty surrounding the values of the inputs to the model, which are often assumed known. We develop general modelling methodology with uncertain inputs in the context of the Bayes linear paradigm, which involves adjustment of second-order belief specifications over all quantities of interest only, without the requirement for probabilistic specifications. In particular, we propose an extension of commonly-employed second-order modelling assumptions to the case of uncertain inputs, with explicit implementation in the context of regression analysis, stochastic process modelling, and statistical emulation. We apply the methodology to a regression model for extracting aluminium by electrolysis, and emulation of the motivating epidemiological simulator chain to model the impact of an airborne infectious disease.
Data aggregation, also known as meta analysis, is widely used to combine knowledge on parameters shared in common (e.g., average treatment effect) between multiple studies. In this paper, we introduce an attractive data aggregation scheme that pools summary statistics from various existing studies. Our scheme informs the design of new validation studies and yields us unbiased estimators for the shared parameters. In our setup, each existing study applies a LASSO regression to select a parsimonious model from a large set of covariates. It is well known that post-hoc estimators, in the selected model, tend to be biased. We show that a novel technique called \textit{data carving} yields us a new unbiased estimator by aggregating simple summary statistics from all existing studies. Our estimator has two key features: (a) we make the fullest possible use of data, from all studies, without the risk of bias from model selection; (b) we enjoy the added benefit of individual data privacy, because raw data from these studies need not be shared or stored for efficient estimation.
Model independent techniques for constructing background data templates using generative models have shown great promise for use in searches for new physics processes at the LHC. We introduce a major improvement to the CURTAINs method by training the conditional normalizing flow between two side-band regions using maximum likelihood estimation instead of an optimal transport loss. The new training objective improves the robustness and fidelity of the transformed data and is much faster and easier to train. We compare the performance against the previous approach and the current state of the art using the LHC Olympics anomaly detection dataset, where we see a significant improvement in sensitivity over the original CURTAINs method. Furthermore, CURTAINsF4F requires substantially less computational resources to cover a large number of signal regions than other fully data driven approaches. When using an efficient configuration, an order of magnitude more models can be trained in the same time required for ten signal regions, without a significant drop in performance.
Combination of several anti-cancer treatments has typically been presumed to have enhanced drug activity. Motivated by a real clinical trial, this paper considers phase I-II dose finding designs for dual-agent combinations, where one main objective is to characterize both the toxicity and efficacy profiles. We propose a two-stage Bayesian adaptive design that accommodates a change of patient population in-between. In stage I, we estimate a maximum tolerated dose combination using the escalation with overdose control (EWOC) principle. This is followed by a stage II, conducted in a new yet relevant patient population, to find the most efficacious dose combination. We implement a robust Bayesian hierarchical random-effects model to allow sharing of information on the efficacy across stages, assuming that the related parameters are either exchangeable or nonexchangeable. Under the assumption of exchangeability, a random-effects distribution is specified for the main effects parameters to capture uncertainty about the between-stage differences. The inclusion of nonexchangeability assumption further enables that the stage-specific efficacy parameters have their own priors. The proposed methodology is assessed with an extensive simulation study. Our results suggest a general improvement of the operating characteristics for the efficacy assessment, under a conservative assumption about the exchangeability of the parameters \textit{a priori}
We propose a model of treatment interference where the response of a unit depends only on its treatment status and the statuses of units within its K-neighborhood. Current methods for detecting interference include carefully designed randomized experiments and conditional randomization tests on a set of focal units. We give guidance on how to choose focal units under this model of interference. We then conduct a simulation study to evaluate the efficacy of existing methods for detecting network interference. We show that this choice of focal units leads to powerful tests of treatment interference which outperform current experimental methods.
Determining causal effects of interventions onto outcomes from real-world, observational (non-randomized) data, e.g., treatment repurposing using electronic health records, is challenging due to underlying bias. Causal deep learning has improved over traditional techniques for estimating individualized treatment effects (ITE). We present the Doubly Robust Variational Information-theoretic Deep Adversarial Learning (DR-VIDAL), a novel generative framework that combines two joint models of treatment and outcome, ensuring an unbiased ITE estimation even when one of the two is misspecified. DR-VIDAL integrates: (i) a variational autoencoder (VAE) to factorize confounders into latent variables according to causal assumptions; (ii) an information-theoretic generative adversarial network (Info-GAN) to generate counterfactuals; (iii) a doubly robust block incorporating treatment propensities for outcome predictions. On synthetic and real-world datasets (Infant Health and Development Program, Twin Birth Registry, and National Supported Work Program), DR-VIDAL achieves better performance than other non-generative and generative methods. In conclusion, DR-VIDAL uniquely fuses causal assumptions, VAE, Info-GAN, and doubly robustness into a comprehensive, performant framework. Code is available at: //github.com/Shantanu48114860/DR-VIDAL-AMIA-22 under MIT license.
Many recent developments in causal inference, and functional estimation problems more generally, have been motivated by the fact that classical one-step (first-order) debiasing methods, or their more recent sample-split double machine-learning avatars, can outperform plugin estimators under surprisingly weak conditions. These first-order corrections improve on plugin estimators in a black-box fashion, and consequently are often used in conjunction with powerful off-the-shelf estimation methods. These first-order methods are however provably suboptimal in a minimax sense for functional estimation when the nuisance functions live in Holder-type function spaces. This suboptimality of first-order debiasing has motivated the development of "higher-order" debiasing methods. The resulting estimators are, in some cases, provably optimal over Holder-type spaces, but both the estimators which are minimax-optimal and their analyses are crucially tied to properties of the underlying function space. In this paper we investigate the fundamental limits of structure-agnostic functional estimation, where relatively weak conditions are placed on the underlying nuisance functions. We show that there is a strong sense in which existing first-order methods are optimal. We achieve this goal by providing a formalization of the problem of functional estimation with black-box nuisance function estimates, and deriving minimax lower bounds for this problem. Our results highlight some clear tradeoffs in functional estimation -- if we wish to remain agnostic to the underlying nuisance function spaces, impose only high-level rate conditions, and maintain compatibility with black-box nuisance estimators then first-order methods are optimal. When we have an understanding of the structure of the underlying nuisance functions then carefully constructed higher-order estimators can outperform first-order estimators.
Bayesian optimization is a class of global optimization techniques. In Bayesian optimization, the underlying objective function is modeled as a realization of a Gaussian process. Although the Gaussian process assumption implies a random distribution of the Bayesian optimization outputs, quantification of this uncertainty is rarely studied in the literature. In this work, we propose a novel approach to assess the output uncertainty of Bayesian optimization algorithms, which proceeds by constructing confidence regions of the maximum point (or value) of the objective function. These regions can be computed efficiently, and their confidence levels are guaranteed by the uniform error bounds for sequential Gaussian process regression newly developed in the present work. Our theory provides a unified uncertainty quantification framework for all existing sequential sampling policies and stopping criteria.
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