Journal of Statistical Planning and Inference

The stepped wedge design is increasingly popular in pragmatic trials and implementation science research studies for evaluating system-level interventions that are perceived to be beneficial to patient populations. An important step in planning a stepped wedge design is to understand the efficiency of the treatment effect estimator and hence the power of the study. We develop several novel analytical results for designing stepped wedge cluster randomized trials analyzed through generalized estimating equations under a misspecified working independence correlation structure...

Expression quantitative trait locus (eQTL) analysis is a useful tool to identify genetic loci that are associated with gene expression levels. Large collaborative efforts such as the Genotype-Tissue Expression (GTEx) project provide valuable resources for eQTL analysis in different tissues. Most existing methods, however, either focus on one tissue at a time, or analyze multiple tissues to identify eQTLs jointly present in multiple tissues. There is a lack of powerful methods to identify eQTLs in a target tissue while effectively borrowing strength from auxiliary tissues...

The continuous net reclassification improvement (NRI) statistic is a popular model change measure that was developed to assess the incremental value of new factors in a risk prediction model. Two prominent statistical issues identified in the literature call the utility of this measure into question: (1) it is not a proper scoring function and (2) it has a high false positive rate when testing whether new factors contribute to the risk model. For binary response regression models, these subjects are interrogated and a modification of the continuous NRI, guided by the likelihood-based score residual, is proposed to address these issues...

We introduce a novel procedure to perform Bayesian non-parametric inference with right-censored data, the beta-Stacy bootstrap . This approximates the posterior law of summaries of the survival distribution (e.g. the mean survival time). More precisely, our procedure approximates the joint posterior law of functionals of the beta-Stacy process, a non-parametric process prior that generalizes the Dirichlet process and that is widely used in survival analysis. The beta-Stacy bootstrap generalizes and unifies other common Bayesian bootstraps for complete or censored data based on non-parametric priors...

When no single outcome is sufficient to capture the multidimensional impairments of a disease, investigators often rely on multiple outcomes for comprehensive assessment of global disease status. Methods for assessing covariate effects on global disease status include the composite outcome and global test procedures. One global test procedure is the O'Brien's rank-sum test, which combines information from multiple outcomes using a global rank-sum score. However, existing methods for the global rank-sum do not lend themselves to regression modeling...

Bayesian response adaptive clinical trials are currently evaluating experimental therapies for several diseases. Adaptive decisions, such as pre-planned variations of the randomization probabilities, attempt to accelerate the development of new treatments. The design of response adaptive trials, in most cases, requires time consuming simulation studies to describe operating characteristics, such as type I/II error rates, across plausible scenarios. We investigate large sample approximations of pivotal operating characteristics in Bayesian Uncertainty directed trial Designs (BUDs)...

Doubly censored data are very common in epidemiology studies. Ignoring censorship in the analysis may lead to biased parameter estimation. In this paper, we highlight that the publicly available COVID19 data may involve high percentage of double-censoring and point out the importance of dealing with such missing information in order to achieve better forecasting results. Existing statistical methods for doubly censored data may suffer from the convergence problems of the EM algorithms or may not be good enough for small sample sizes...

We study variance estimation and associated confidence intervals for parameters characterizing genetic effects from genome-wide association studies (GWAS) in misspecified mixed model analysis. Previous studies have shown that, in spite of the model misspecification, certain quantities of genetic interests are consistently estimable, and consistent estimators of these quantities can be obtained using the restricted maximum likelihood (REML) method under a misspecified linear mixed model. However, the asymptotic variance of such a REML estimator is complicated and not ready to be implemented for practical use...

Spike-and-slab priors model predictors as arising from a mixture of distributions: those that should (slab) or should not (spike) remain in the model. The spike-and-slab lasso (SSL) is a mixture of double exponentials, extending the single lasso penalty by imposing different penalties on parameters based on their inclusion probabilities. The SSL was extended to Generalized Linear Models (GLM) for application in genetics/genomics, and can handle many highly correlated predictors of a scalar outcome, but does not incorporate these relationships into variable selection...

We propose a construction of simultaneous confidence bands (SCBs) for functional parameters over arbitrary dimensional compact domains using the Gaussian Kinematic formula of t -processes (tGKF). Although the tGKF relies on Gaussianity, we show that a central limit theorem (CLT) for the parameter of interest is enough to obtain asymptotically precise covering even if the observations are non-Gaussian processes. As a proof of concept we study the functional signal-plus-noise model and derive a CLT for an estimator of the Lipshitz-Killing curvatures, the only data-dependent quantities in the tGKF...

We introduce new shape-constrained classes of distribution functions on <mml:math xmlns:mml="https://www.w3.org/1998/Math/MathML"><mml:mi>R</mml:mi></mml:math> , the bi- s *-concave classes. In parallel to results of Dümbgen et al. (2017) for what they called the class of bi-log-concave distribution functions, we show that every s -concave density f has a bi- s *-concave distribution function F for s * ≤ s /( s + 1). Confidence bands building on existing nonparametric confidence bands, but accounting for the shape constraint of bi- s *-concavity, are also considered...

Quantum state tomography, which aims to estimate quantum states that are described by density matrices, plays an important role in quantum science and quantum technology. This paper examines the eigenspace estimation and the reconstruction of large low-rank density matrix based on Pauli measurements. Both ordinary principal component analysis (PCA) and iterative thresholding sparse PCA (ITSPCA) estimators of the eigenspace are studied, and their respective convergence rates are established. In particular, we show that the ITSPCA estimator is rate-optimal...

We introduce an estimation method of covariance matrices in a high-dimensional setting, i.e., when the dimension of the matrix, p , is larger than the sample size n . Specifically, we propose an orthogonally equivariant estimator. The eigenvectors of such estimator are the same as those of the sample covariance matrix. The eigenvalue estimates are obtained from an adjusted profile likelihood function derived by approximating the integral of the density function of the sample covariance matrix over its eigenvectors, which is a challenging problem in its own right...

In many trials, the duration between patient enrolment and an event occurring is used as the efficacy endpoint. Common endpoints of this type include the time until relapse, progression to the next stage of a disease, or time until remission. The criteria of an event may be defined by multiple components, one or more of which may be a continuous measurement being above or below a threshold. Typical analyses consider all components as binary variables and record the first time at which the patient has an event...

In a regression model for treatment outcome in a randomized clinical trial, a treatment effect modifier is a covariate that has an interaction with the treatment variable, implying that the treatment efficacies vary across values of such a covariate. In this paper, we present a method for determining a composite variable from a set of baseline covariates, that can have a nonlinear association with the treatment outcome, and acts as a composite treatment effect modifier. We introduce a parsimonious generalization of the single-index models that targets the effect of the interaction between the treatment conditions and the vector of covariates on the outcome, a single-index model with multiple-links (SIMML) that estimates a single linear combination of the covariates (i...

The current penalized regression methods for selecting predictor variables and estimating the associated regression coefficients in the sparse Cox model are mainly based on partial likelihood. In this paper, a bias-corrected empirical likelihood method is proposed for the sparse Cox model in conjunction with appropriate penalty functions when the dimensionality of data is high. Theoretical properties of the resulting estimator for the large sample are proved. Simulation studies suggest that penalized empirical likelihood works better than partial likelihood in terms of selecting correct predictors without introducing more model errors...

Precision medicine, aka stratified/personalized medicine, is becoming more pronounced in the medical field due to advancement in computational ability to learn about patient genomic backgrounds. A biomaker, i.e. a type of biological process indicator, is often used in precision medicine to classify patient population into several subgroups. The aim of precision medicine is to tailor treatment regimes for different patient subgroups who suffer from the same disease. A multi-arm design could be conducted to explore the effect of treatment regimes on different biomarker subgroups...

Connectivity studies of the brain are usually based on functional Magnetic Resonance Imaging (fMRI) experiments involving many subjects. These studies need to take into account not only the interaction between areas of a single brain but also the differences amongst those subjects. In this paper we develop a methodology called the group-structure (GS) approach that models possible heterogeneity between subjects and searches for distinct homogeneous sub-groups according to some measure that reflects the connectivity maps...

As the US health care system undergoes unprecedented changes, the need for adequately powered studies to understand the multiple levels of main and interaction factors that influence patient and other care outcomes in hierarchical settings has taken center stage. We consider two-level models where n lower-level units are nested within each of J higher-level clusters (e.g. patients within practices and practices within networks) and where two factors may have arbitrary a and b factor levels, respectively. Both factors may represent a × b treatment combinations, or one of them may be a pretreatment covariate...

We introduce a rank-based bent linear regression with an unknown change point. Using a linear reparameterization technique, we propose a rank-based estimate that can make simultaneous inference on all model parameters, including the location of the change point, in a computationally efficient manner. We also develop a score-like test for the existence of a change point, based on a weighted CUSUM process. This test only requires fitting the model under the null hypothesis in absence of a change point, thus it is computationally more efficient than likelihood-ratio type tests...