The New England Journal of Statistics in Data Science

Variable selection in large-dimensional data has been extensively studied in different settings over the past decades. In a recent article, Shokoohi et. al. [29, DOI:10.1214/18-AOAS1198] proposed a method for variable selection in finite mixture of accelerated failure time regression models for studies on time-to-event data to capture heterogeneity within the population and account for censoring. In this paper, we introduce the fmrs package, which implements the variable selection methodology for such models. Furthermore, as a byproduct, the fmrs package facilitates variable selection in finite mixture regression models. The package also incorporates a tuning parameter selection mechanism based on component-wise bic. Commonly used penalties, such as Least Absolute Shrinkage and Selection Operator, and Smoothly Clipped Absolute Deviation, are integrated into fmrs. Additionally, the package offers an option for non-mixture regression models. The C language is chosen to boost the optimization speed. We provide an overview of the fmrs principles and the strategies employed for optimization. Hands-on illustrations are presented to help users get acquainted with fmrs. Finally, we apply fmrs to a lung cancer dataset and observe that a two-component mixture model reveals a subgroup with a more aggressive form of the disease, displaying a lower survival time.

Graphical models have witnessed significant growth and usage in spatial data science for modeling data referenced over a massive number of spatial-temporal coordinates. Much of this literature has focused on a single or relatively few spatially dependent outcomes. Recent attention has focused upon addressing modeling and inference for substantially large number of outcomes. While spatial factor models and multivariate basis expansions occupy a prominent place in this domain, this article elucidates a recent approach, graphical Gaussian Processes, that exploits the notion of conditional independence among a very large number of spatial processes to build scalable graphical models for fully model-based Bayesian analysis of multivariate spatial data.

Basket trials have captured much attention in oncology research in recent years, as advances in health technology have opened up the possibility of classification of patients at the genomic level. Bayesian methods are particularly prevalent in basket trials as the hierarchical structure is adapted to basket trials to allow for information borrowing. In this article, we extend the Bayesian methods to basket trials with treatment and control arms for continuous endpoints, which are often the cases in clinical trials for rare diseases. To account for the imbalance in the covariates which are potentially strong predictors but not stratified in a randomized trial, our models make adjustments for these covariates, and allow different coefficients across baskets. In addition, comparisons are drawn between two-stage design and one-stage design for the four Bayesian methods. Extensive simulation studies are conducted to examine the empirical performance of all models under consideration. A real data analysis is carried out to further demonstrate the usefulness of the Bayesian methods.

In diagnostic imaging drug developments, the imaging scan read data in controlled imaging drug clinical trials includes test positive and test negative. Broadly speaking, the standard of reference data are either presence or absence of a disease or clinical condition. Together, these data are used to assess the diagnostic performance of an investigational imaging drug in a controlled imaging drug clinical trial. For those imaging scan read data that cannot be called positive/negative, the “indeterminate” category is commonly used to cover imaging results that may be considered intermediate, indeterminate, or uninterpretable. Similarly, for those standard of reference data that cannot be categorized into presence/absence including uncollected or unavailable reference standard data, the “indeterminate” category may be used. Historically, little attention has been paid to the indeterminate imaging scan read data as they are generally rare or considered irrelevant though they are related to scanned subjects and can be informative. Subjects lack the standard of reference are simply excluded as such the study only reports the analysis results in subjects with available standard of reference data, known as completer analysis, similar to evaluable subjects seen in controlled trials for drug developments.

Designing longitudinal studies is generally a very challenging problem because of the complex optimization problems. We show the popular nature-inspired metaheuristic algorithm, Particle Swarm Optimization (PSO), can find different types of optimal exact designs for longitudinal studies with different correlation structures for different types of models. In particular, we demonstrate PSO-generated D-optimal longitudinal studies for the widely used Michaelis-Menten model with various correlation structures agree with the reported analytically derived locally D-optimal designs in the literature when there are only 2 observations per subject, and their numerical D-optimal designs when there are 3 and 4 observations per subject. We further show the usefulness of PSO by applying it to generate new locally D-optimal designs to estimate model parameters when there are 5 or more observations per subject. Additionally, we find various optimal longitudinal designs for a growth curve model commonly used in animal studies and for a nonlinear HIV dynamic model for studying T-cells in AIDS subjects. In particular, c-optimal exact designs for estimating one or more functions of model parameters (c-optimality) were found, along with other types of multiple objectives optimal designs.

The continuation-ratio (CR) model is frequently used in dose response studies to model a three-category outcome as the dose levels vary. Design issues for a CR model defined on an unrestricted dose interval have been discussed for estimating model parameters or a selected function of the model parameters. This paper uses metaheuristics to address design issues for a CR model defined on any compact dose interval when there are one or more objectives in the study and some are more important than others. Specifically, we use an exemplary nature-inspired metaheuristic algorithm called particle swarm optimization (PSO) to find locally optimal designs for estimating a few interesting functions of the model parameters, such as the most effective dose ($MED$), the maximum tolerated dose ($MTD$) and for estimating all parameters in a CR model. We demonstrate that PSO can efficiently find locally multiple-objective optimal designs for a CR model on various dose intervals and a small simulation study shows it tends to outperform the popular deterministic cocktail algorithm (CA) and another competitive metaheuristic algorithm called differential evolutionary (DE). We also discuss hybrid algorithms and their flexible applications to design early Phase 2 trials or tackle biomedical problems, such as different strategies for handling the recent pandemic.

Approximate confidence distribution computing (ACDC) offers a new take on the rapidly developing field of likelihood-free inference from within a frequentist framework. The appeal of this computational method for statistical inference hinges upon the concept of a confidence distribution, a special type of estimator which is defined with respect to the repeated sampling principle. An ACDC method provides frequentist validation for computational inference in problems with unknown or intractable likelihoods. The main theoretical contribution of this work is the identification of a matching condition necessary for frequentist validity of inference from this method. In addition to providing an example of how a modern understanding of confidence distribution theory can be used to connect Bayesian and frequentist inferential paradigms, we present a case to expand the current scope of so-called approximate Bayesian inference to include non-Bayesian inference by targeting a confidence distribution rather than a posterior. The main practical contribution of this work is the development of a data-driven approach to drive ACDC in both Bayesian or frequentist contexts. The ACDC algorithm is data-driven by the selection of a data-dependent proposal function, the structure of which is quite general and adaptable to many settings. We explore three numerical examples that both verify the theoretical arguments in the development of ACDC and suggest instances in which ACDC outperform approximate Bayesian computing methods computationally.

In this paper, we propose a method for wavelet denoising of signals contaminated with Gaussian noise when prior information about the ${L^{2}}$-energy of the signal is available. Assuming the independence model, according to which the wavelet coefficients are treated individually, we propose simple, level-dependent shrinkage rules that turn out to be Γ-minimax for a suitable class of priors.