Across research disciplines, cluster randomized trials (CRTs) are commonly implemented to evaluate interventions delivered to groups of participants, such as communities and clinics. Despite advances in the design and analysis of CRTs, several challenges remain. First, there are many possible ways to specify the causal effect of interest (e.g., at the individual-level or at the cluster-level). Second, the theoretical and practical performance of common methods for CRT analysis remain poorly understood. Here, we present a general framework to formally define an array of causal effects in terms of summary measures of counterfactual outcomes. Next, we provide a comprehensive overview of CRT estimators, including the t-test, generalized estimating equations (GEE), augmented-GEE, and targeted maximum likelihood estimation (TMLE). Using finite sample simulations, we illustrate the practical performance of these estimators for different causal effects and when, as commonly occurs, there are limited numbers of clusters of different sizes. Finally, our application to data from the Preterm Birth Initiative (PTBi) study demonstrates the real-world impact of varying cluster sizes and targeting effects at the cluster-level or at the individual-level. Specifically, the relative effect of the PTBI intervention was 0.81 at the cluster-level, corresponding to a 19% reduction in outcome incidence, and was 0.66 at the individual-level, corresponding to a 34% reduction in outcome risk. Given its flexibility to estimate a variety of user-specified effects and ability to adaptively adjust for covariates for precision gains while maintaining Type-I error control, we conclude TMLE is a promising tool for CRT analysis.
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Estimating heterogeneous treatment effects is crucial for informing personalized treatment strategies and policies. While multiple studies can improve the accuracy and generalizability of results, leveraging them for estimation is statistically challenging. Existing approaches often assume identical heterogeneous treatment effects across studies, but this may be violated due to various sources of between-study heterogeneity, including differences in study design, confounders, and sample characteristics. To this end, we propose a unifying framework for multi-study heterogeneous treatment effect estimation that is robust to between-study heterogeneity in the nuisance functions and treatment effects. Our approach, the multi-study R-learner, extends the R-learner to obtain principled statistical estimation with modern machine learning (ML) in the multi-study setting. The multi-study R-learner is easy to implement and flexible in its ability to incorporate ML for estimating heterogeneous treatment effects, nuisance functions, and membership probabilities, which borrow strength across heterogeneous studies. It achieves robustness in confounding adjustment through its loss function and can leverage both randomized controlled trials and observational studies. We provide asymptotic guarantees for the proposed method in the case of series estimation and illustrate using real cancer data that it has the lowest estimation error compared to existing approaches in the presence of between-study heterogeneity.
Reliable probabilistic primality tests are fundamental in public-key cryptography. In adversarial scenarios, a composite with a high probability of passing a specific primality test could be chosen. In such cases, we need worst-case error estimates for the test. However, in many scenarios the numbers are randomly chosen and thus have significantly smaller error probability. Therefore, we are interested in average case error estimates. In this paper, we establish such bounds for the strong Lucas primality test, as only worst-case, but no average case error bounds, are currently available. This allows us to use this test with more confidence. We examine an algorithm that draws odd $k$-bit integers uniformly and independently, runs $t$ independent iterations of the strong Lucas test with randomly chosen parameters, and outputs the first number that passes all $t$ consecutive rounds. We attain numerical upper bounds on the probability on returing a composite. Furthermore, we consider a modified version of this algorithm that excludes integers divisible by small primes, resulting in improved bounds. Additionally, we classify the numbers that contribute most to our estimate.
The problem of generalization and transportation of treatment effect estimates from a study sample to a target population is central to empirical research and statistical methodology. In both randomized experiments and observational studies, weighting methods are often used with this objective. Traditional methods construct the weights by separately modeling the treatment assignment and study selection probabilities and then multiplying functions (e.g., inverses) of their estimates. In this work, we provide a justification and an implementation for weighting in a single step. We show a formal connection between this one-step method and inverse probability and inverse odds weighting. We demonstrate that the resulting estimator for the target average treatment effect is consistent, asymptotically Normal, multiply robust, and semiparametrically efficient. We evaluate the performance of the one-step estimator in a simulation study. We illustrate its use in a case study on the effects of physician racial diversity on preventive healthcare utilization among Black men in California. We provide R code implementing the methodology.
A treatment policy defines when and what treatments are applied to affect some outcome of interest. Data-driven decision-making requires the ability to predict what happens if a policy is changed. Existing methods that predict how the outcome evolves under different scenarios assume that the tentative sequences of future treatments are fixed in advance, while in practice the treatments are determined stochastically by a policy and may depend, for example, on the efficiency of previous treatments. Therefore, the current methods are not applicable if the treatment policy is unknown or a counterfactual analysis is needed. To handle these limitations, we model the treatments and outcomes jointly in continuous time, by combining Gaussian processes and point processes. Our model enables the estimation of a treatment policy from observational sequences of treatments and outcomes, and it can predict the interventional and counterfactual progression of the outcome after an intervention on the treatment policy (in contrast with the causal effect of a single treatment). We show with real-world and semi-synthetic data on blood glucose progression that our method can answer causal queries more accurately than existing alternatives.
Bayesian inference and the use of posterior or posterior predictive probabilities for decision making have become increasingly popular in clinical trials. The current approach toward Bayesian clinical trials is, however, a hybrid Bayesian-frequentist approach where the design and decision criteria are assessed with respect to frequentist operating characteristics such as power and type I error rate. These operating characteristics are commonly obtained via simulation studies. In this article we propose methodology to utilize large sample theory of the posterior distribution to define simple parametric models for the sampling distribution of the Bayesian test statistics, i.e., posterior tail probabilities. The parameters of these models are then estimated using a small number of simulation scenarios, thereby refining these models to capture the sampling distribution for small to moderate sample size. The proposed approach toward assessment of operating characteristics and sample size determination can be considered as simulation-assisted rather than simulation-based and significantly reduces the computational burden for design of Bayesian trials.
In this paper, we use the optimization formulation of nonlinear Kalman filtering and smoothing problems to develop second-order variants of iterated Kalman smoother (IKS) methods. We show that Newton's method corresponds to a recursion over affine smoothing problems on a modified state-space model augmented by a pseudo measurement. The first and second derivatives required in this approach can be efficiently computed with widely available automatic differentiation tools. Furthermore, we show how to incorporate line-search and trust-region strategies into the proposed second-order IKS algorithm in order to regularize updates between iterations. Finally, we provide numerical examples to demonstrate the method's efficiency in terms of runtime compared to its batch counterpart.
We consider the problem of estimating a scalar target parameter in the presence of nuisance parameters. Replacing the unknown nuisance parameter with a nonparametric estimator, e.g.,a machine learning (ML) model, is convenient but has shown to be inefficient due to large biases. Modern methods, such as the targeted minimum loss-based estimation (TMLE) and double machine learning (DML), achieve optimal performance under flexible assumptions by harnessing ML estimates while mitigating the plug-in bias. To avoid a sub-optimal bias-variance trade-off, these methods perform a debiasing step of the plug-in pre-estimate. Existing debiasing methods require the influence function of the target parameter as input. However, deriving the IF requires specialized expertise and thus obstructs the adaptation of these methods by practitioners. We propose a novel way to debias plug-in estimators which (i) is efficient, (ii) does not require the IF to be implemented, (iii) is computationally tractable, and therefore can be readily adapted to new estimation problems and automated without analytic derivations by the user. We build on the TMLE framework and update a plug-in estimate with a regularized likelihood maximization step over a nonparametric model constructed with a reproducing kernel Hilbert space (RKHS), producing an efficient plug-in estimate for any regular target parameter. Our method, thus, offers the efficiency of competing debiasing techniques without sacrificing the utility of the plug-in approach.
With increasing automation, drivers' role progressively transitions from active operators to passive system supervisors, affecting their behaviour and cognitive processes. This study aims to understand better attention allocation and perceived cognitive load in manual, L2, and L3 driving in a realistic environment. We conducted a test-track experiment with 30 participants. While driving a prototype automated vehicle, participants were exposed to a passive auditory oddball task and their EEG was recorded. We studied the P3a ERP component elicited by novel environmental cues, an index of attention resources used to process the stimuli. The self-reported cognitive load was assessed using the NASA-TLX. Our findings revealed no significant difference in perceived cognitive load between manual and L2 driving, with L3 driving demonstrating a lower self-reported cognitive load. Despite this, P3a mean amplitude was highest during manual driving, indicating greater attention allocation towards processing environmental sounds compared to L2 and L3 driving. We argue that the need to integrate environmental information might be attenuated in L2 and L3 driving. Further empirical evidence is necessary to understand whether the decreased processing of environmental stimuli is due to top-down attention control leading to attention withdrawal or a lack of available resources due to high cognitive load. To the best of our knowledge, this study is the first attempt to use the passive oddball paradigm outside the laboratory. The insights of this study have significant implications for automation safety and user interface design.
Mean-based estimators of the causal effect in a completely randomized experiment (e.g., the difference-in-means estimator) may behave poorly if the potential outcomes have a heavy-tail, or contain outliers. We study an alternative estimator by Rosenbaum that estimates the constant additive treatment effect by inverting a randomization test using ranks. By investigating the breakdown point and asymptotic relative efficiency of this rank-based estimator, we show that it is provably robust against heavy-tailed potential outcomes, and has variance that is asymptotically, in the worst case, at most about 1.16 times that of the difference-in-means estimator; and its variance can be much smaller when the potential outcomes are not light-tailed. We further derive a consistent estimator of the asymptotic standard error for Rosenbaum's estimator which yields a readily computable confidence interval for the treatment effect. Further, we study a regression adjusted version of Rosenbaum's estimator to incorporate additional covariate information in randomization inference. We prove gain in efficiency by this regression adjustment method under a linear regression model. We illustrate through synthetic and real data that, unlike the mean-based estimators, these rank-based estimators (both unadjusted or regression adjusted) are efficient and robust against heavy-tailed distributions, contamination, and model misspecification.
A proper fusion of complex data is of interest to many researchers in diverse fields, including computational statistics, computational geometry, bioinformatics, machine learning, pattern recognition, quality management, engineering, statistics, finance, economics, etc. It plays a crucial role in: synthetic description of data processes or whole domains, creation of rule bases for approximate reasoning tasks, reaching consensus and selection of the optimal strategy in decision support systems, imputation of missing values, data deduplication and consolidation, record linkage across heterogeneous databases, and clustering. This open-access research monograph integrates the spread-out results from different domains using the methodology of the well-established classical aggregation framework, introduces researchers and practitioners to Aggregation 2.0, as well as points out the challenges and interesting directions for further research.
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