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A central obstacle in the objective assessment of treatment effect (TE) estimators in randomized control trials (RCTs) is the lack of ground truth (or validation set) to test their performance. In this paper, we provide a novel cross-validation-like methodology to address this challenge. The key insight of our procedure is that the noisy (but unbiased) difference-of-means estimate can be used as a ground truth "label" on a portion of the RCT, to test the performance of an estimator trained on the other portion. We combine this insight with an aggregation scheme, which borrows statistical strength across a large collection of RCTs, to present an end-to-end methodology for judging an estimator's ability to recover the underlying treatment effect. We evaluate our methodology across 709 RCTs implemented in the Amazon supply chain. In the corpus of AB tests at Amazon, we highlight the unique difficulties associated with recovering the treatment effect due to the heavy-tailed nature of the response variables. In this heavy-tailed setting, our methodology suggests that procedures that aggressively downweight or truncate large values, while introducing bias, lower the variance enough to ensure that the treatment effect is more accurately estimated.

We consider the conditional treatment effect for competing risks data in observational studies. While it is described as a constant difference between the hazard functions given the covariates, we do not assume specific functional forms for the covariates. We derive the efficient score for the treatment effect using modern semiparametric theory, as well as two doubly robust scores with respect to 1) the assumed propensity score for treatment and the censoring model, and 2) the outcome models for the competing risks. An important asymptotic result regarding the estimators is rate double robustness, in addition to the classical model double robustness. Rate double robustness enables the use of machine learning and nonparametric methods in order to estimate the nuisance parameters, while preserving the root-$n$ asymptotic normality of the estimators for inferential purposes. We study the performance of the estimators using simulation. The estimators are applied to the data from a cohort of Japanese men in Hawaii followed since 1960s in order to study the effect of mid-life drinking behavior on late life cognitive outcomes.

Federated learning of causal estimands may greatly improve estimation efficiency by aggregating estimates from multiple study sites, but robustness to extreme estimates is vital for maintaining consistency. We develop a federated adaptive causal estimation (FACE) framework to incorporate heterogeneous data from multiple sites to provide treatment effect estimation and inference for a target population of interest. Our strategy is communication-efficient and privacy-preserving and allows for flexibility in the specification of the target population. Our method accounts for site-level heterogeneity in the distribution of covariates through density ratio weighting. To safely aggregate estimates from all sites and avoid negative transfer, we introduce an adaptive procedure of weighing the estimators constructed using data from the target and source populations through a penalized regression on the influence functions, which achieves 1) consistency and 2) optimal efficiency. We illustrate FACE by conducting a comparative effectiveness study of BNT162b2 (Pfizer) and mRNA-1273 (Moderna) vaccines on COVID-19 outcomes in U.S. veterans using electronic health records from five VA sites.

When are inferences (whether Direct-Likelihood, Bayesian, or Frequentist) obtained from partial data valid? This paper answers this question by offering a new theory about inference with missing data. It proves that as the sample size increases and the extent of missingness decreases, the mean-loglikelihood function generated by partial data and that ignores the missingness mechanism will almost surely converge uniformly to that which would have been generated by complete data; and if the data are Missing at Random, this convergence depends only on sample size. Thus, inferences on partial data, such as posterior modes, uncertainty estimates, confidence intervals, likelihood ratios, and indeed, all quantities or features derived from the partial-data loglikelihood function, will approximate their true values (what they would have been given complete data). This adds to previous research which has only proved the consistency of the posterior mode. Practical implications of this result are discussed, and the theory is tested on a previous study of International Human Rights Law.

Stationary points embedded in the derivatives are often critical for a model to be interpretable and may be considered as key features of interest in many applications. We propose a semiparametric Bayesian model to efficiently infer the locations of stationary points of a nonparametric function, while treating the function itself as a nuisance parameter. We use Gaussian processes as a flexible prior for the underlying function and impose derivative constraints to control the function's shape via conditioning. We develop an inferential strategy that intentionally restricts estimation to the case of at least one stationary point, bypassing possible mis-specifications in the number of stationary points and avoiding the varying dimension problem that often brings in computational complexity. We illustrate the proposed methods using simulations and then apply the method to the estimation of event-related potentials (ERP) derived from electroencephalography (EEG) signals. We show how the proposed method automatically identifies characteristic components and their latencies at the individual level, which avoids the excessive averaging across subjects which is routinely done in the field to obtain smooth curves. By applying this approach to EEG data collected from younger and older adults during a speech perception task, we are able to demonstrate how the time course of speech perception processes changes with age.

Parameters of the covariance kernel of a Gaussian process model often need to be estimated from the data generated by an unknown Gaussian process. We consider fixed-domain asymptotics of the maximum likelihood estimator of the scale parameter under smoothness misspecification. If the covariance kernel of the data-generating process has smoothness $\nu_0$ but that of the model has smoothness $\nu \geq \nu_0$, we prove that the expectation of the maximum likelihood estimator is of the order $N^{2(\nu-\nu_0)/d}$ if the $N$ observation points are quasi-uniform in $[0, 1]^d$. This indicates that maximum likelihood estimation of the scale parameter alone is sufficient to guarantee the correct rate of decay of the conditional variance. We also discuss a connection the expected maximum likelihood estimator has to Driscoll's theorem on sample path properties of Gaussian processes. The proofs are based on reproducing kernel Hilbert space techniques and worst-case case rates for approximation in Sobolev spaces.

Time-to-event endpoints show an increasing popularity in phase II cancer trials. The standard statistical tool for such one-armed survival trials is the one-sample log-rank test. Its distributional properties are commonly derived in the large sample limit. It is however known from the literature, that the asymptotical approximations suffer when sample size is small. There have already been several attempts to address this problem. While some approaches do not allow easy power and sample size calculations, others lack a clear theoretical motivation and require further considerations. The problem itself can partly be attributed to the dependence of the compensated counting process and its variance estimator. For this purpose, we suggest a variance estimator which is uncorrelated to the compensated counting process. Moreover, this and other present approaches to variance estimation are covered as special cases by our general framework. For practical application, we provide sample size and power calculations for any approach fitting into this framework. Finally, we use simulations and real world data to study the empirical type I error and power performance of our methodology as compared to standard approaches.

One of the main tasks of causal inference is estimating well-defined causal parameters. One of the main causal parameters is the average causal effect (ACE) - the expected value of the individual level causal effects in the target population. For binary treatments, the individual level causal effect is defined as contrast between potential outcomes. For continuous outcomes, however, there are many such contrasts in finite samples, thus hampering their use as a useful summary of the causal relationship. Here, we proposed a generalized version of the ACE, where individual level causal effects are defined as the derivative (with respect to the treatment) of the individual level causal dose-response function evaluated at treatment value that the individual has. This definition is equivalent to the conventional definition for binary treatments, but also incorporates continuous treatments. We demonstrate that this quantity can be estimated under conventional causal assumptions and illustrate the theoretical ideas with a simulation study.

We provide guarantees for approximate Gaussian Process (GP) regression resulting from two common low-rank kernel approximations: based on random Fourier features, and based on truncating the kernel's Mercer expansion. In particular, we bound the Kullback-Leibler divergence between an exact GP and one resulting from one of the afore-described low-rank approximations to its kernel, as well as between their corresponding predictive densities, and we also bound the error between predictive mean vectors and between predictive covariance matrices computed using the exact versus using the approximate GP. We provide experiments on both simulated data and standard benchmarks to evaluate the effectiveness of our theoretical bounds.

This paper focuses on the expected difference in borrower's repayment when there is a change in the lender's credit decisions. Classical estimators overlook the confounding effects and hence the estimation error can be magnificent. As such, we propose another approach to construct the estimators such that the error can be greatly reduced. The proposed estimators are shown to be unbiased, consistent, and robust through a combination of theoretical analysis and numerical testing. Moreover, we compare the power of estimating the causal quantities between the classical estimators and the proposed estimators. The comparison is tested across a wide range of models, including linear regression models, tree-based models, and neural network-based models, under different simulated datasets that exhibit different levels of causality, different degrees of nonlinearity, and different distributional properties. Most importantly, we apply our approaches to a large observational dataset provided by a global technology firm that operates in both the e-commerce and the lending business. We find that the relative reduction of estimation error is strikingly substantial if the causal effects are accounted for correctly.