Statistical Theory Commons^™

Efficacy Analysis In Clinical Trials: A Comprehensive Review Of Statistical And Machine Learning Approaches, Dhrubajyoti Ghosh, Samhita Pal

Faculty Articles

Efficacy testing is a cornerstone of clinical trials, ensuring that medical interventions achieve their intended therapeutic effects. Over the decades, a wide range of statistical methodologies have been developed to address the complexities of clinical trial data, including parametric, nonparametric, Bayesian, and machine learning approaches. Parametric methods, such as t-tests, ANOVA, and LMMs, have traditionally been the foundation of efficacy testing due to their efficiency under well-defined assumptions. Nonparametric techniques, including the Friedman test, Brunner-Munzel test, and modern extensions like nparLD, have emerged as robust alternatives, particularly for skewed, ordinal, or non-normal data. Bayesian methodologies have enabled the incorporation of …

A Comparative Study Of Classification Methods For Healthcare Analytics, Xueting Zhao

UNF Graduate Theses and Dissertations

This thesis presents a comparative study of logistic regression, Linear Discriminant Analy- sis (LDA), and Quadratic Discriminant Analysis (QDA) for binary classification in healthcare analytics, integrating theoretical derivation, simulation, and real-data application. A facto- rial simulation study crosses the covariance structure (equal vs. unequal), predictor correla- tion (ρ ∈ {0, 0.5, 0.9}), dimensionality (p ∈ {2, 5, 10}) and sample size (n ∈ {50, 100, 200}) across 54 scenarios with 1,000 Monte Carlo replicates each. Three main findings emerge. Logistic regression and LDA are nearly interchangeable when the assumption of equal-covariance holds. QDA achieves substantially better discrimi- nation when class-specific …

Theoretical Foundations And Applied Performance Of Periodicity-Aware Imputation: Variable Bandpass Block Bootstrap Methods For Incomplete Time Series, Asmaa Ahmad

Electronic Theses & Dissertations (2024 - present)

Time series data are prevalent across a wide range of disciplines, including health surveillance, public policy, and environmental monitoring. In the presence of underlying cyclical patterns, the integrity of time series analysis depends critically on the ability to detect, model, and impute structured missing data without compromising the temporal structure. This dissertation introduces and validates a novel imputation framework that integrates the Variable Bandpass Periodic Block Bootstrap (VBPBB) into multiple imputation procedures, improving the accuracy, robustness, and interpretability of time series models under high rates of missingness and noise. The overarching goal of this dissertation was to develop and evaluate …

Predictive Modeling For Healthcare Data Using Nonlinear Bayesian Methods, Prince Kofi Asare

Theses and Dissertations

Unplanned hospital readmissions represent a significant challenge for healthcare systems, contributing to substantial financial burdens and highlighting gaps in patient care coordination. In the U.S., approximately 20% of Medicare beneficiaries are readmitted within 30 days, costing billions annually. Social determinants of health, such as income, housing stability, and social support, account for up to 80% of health outcomes, yet their integration into predictive models remains underexplored. This study introduces a novel Bayesian framework for predicting 30-day readmission risk, combining Gaussian Process models with spike-and-slab priors and Bayesian Lasso regression with Laplace priors. Utilizing Markov Chain Monte Carlo methods, the approach …

Bayesian Approaches In Multi-State Markov Models And High Dimensional Time-To-Event Data., Yuchen Han

Electronic Theses and Dissertations

This dissertation consists of two projects. The first one involves nonparametric methods on Continuous Time Markov Chains (CTMCs). The second one is centered around Bayesian shrinkage models for detecting prognostic and predictive biomarkers in high-dimensional clinical data. Both these projects build on methods from across the frequentist and Bayesian paradigm to offer novel solutions. In the first project, we aim to model the nonlinear effects of continuous variables within multistate framework in a non-parametrically by appealing to the rich mathematical framework of Reproducing Kernel Hilbert Spaces (RKHS). Then we adapted the classical Representer Theorem to penalized (squared norm) log-likelihood which …

Latent Classification Of Multi-Model Non-Homogeneous Continuous-Time Markov Chains, Joonha Chang

Dissertations and Theses (Open Access)

The continuous-time Markov chain (CTMC) model and latent clustering models are commonly used to study longitudinal measures of categorical outcomes. Because of its simple but powerful Markovian property, CTMC models have been widely used in medical and public health researches. Due to limitations in the standard CTMC model, there have been some studies on non-homogeneous continuous-time Markov chain (NH-CTMC) that utilized time-dependent rates, but the progresses have been limited. NH-CTMC can be more powerful than CTMC by its default nature of time-dependent rate that can be fitted to a wider range of applications in medical studies. In this study, we …

Statistical Inference On Lung Cancer Screening Using The National Lung Screening Trial Data., Farhin Rahman

Electronic Theses and Dissertations

This dissertation consists of three research projects on cancer screening probability modeling. In these projects, the three key modeling parameters (sensitivity, sojourn time, transition density) for cancer screening were estimated, along with the long-term outcomes (including overdiagnosis as one outcome), the optimal screening time/age, the lead time distribution, and the probability of overdiagnosis at the future screening time were simulated to provide a statistical perspective on the effectiveness of cancer screening programs. In the first part of this dissertation, a statistical inference was conducted for male and female smokers using the National Lung Screening Trial (NLST) chest X-ray data. A …

High Dimensional Data Analysis: Variable Screening And Inference, Lei Fang

Theses and Dissertations--Statistics

This dissertation focuses on the problem of high dimensional data analysis, which arises in many fields including genomics, finance, and social sciences. In such settings, the number of features or variables is much larger than the number of observations, posing significant challenges to traditional statistical methods.

To address these challenges, this dissertation proposes novel methods for variable screening and inference. The first part of the dissertation focuses on variable screening, which aims to identify a subset of important variables that are strongly associated with the response variable. Specifically, we propose a robust nonparametric screening method to effectively select the predictors …

Bayesian Methods For Graphical Models With Neighborhood Selection., Sagnik Bhadury

Electronic Theses and Dissertations

Graphical models determine associations between variables through the notion of conditional independence. Gaussian graphical models are a widely used class of such models, where the relationships are formalized by non-null entries of the precision matrix. However, in high-dimensional cases, covariance estimates are typically unstable. Moreover, it is natural to expect only a few significant associations to be present in many realistic applications. This necessitates the injection of sparsity techniques into the estimation method. Classical frequentist methods, like GLASSO, use penalization techniques for this purpose. Fully Bayesian methods, on the contrary, are slow because they require iteratively sampling over a quadratic …

Confidence Interval For The Mean Of A Beta Distribution, Sean Rangel

Electronic Theses and Dissertations

Statistical inference for the mean of a beta distribution has become increasingly popular in various fields of academic research. In this study, we developed a novel statistical model from likelihood-based techniques to evaluate various confidence interval techniques for the mean of a beta distribution. Simulation studies will be implemented to compare the performance of the confidence intervals. In addition to the development and study involving confidence intervals, we will also apply the confidence intervals to real biological data that was gathered by the Department of Biology at Stephen F. Austin State University and provide recommendations on the best practice.

Multi-Level Small Area Estimation Based On Calibrated Hierarchical Likelihood Approach Through Bias Correction With Applications To Covid-19 Data, Nirosha Rathnayake

Theses & Dissertations

Small area estimation (SAE) has been widely used in a variety of applications to draw estimates in geographic domains represented as a metropolitan area, district, county, or state. The direct estimation methods provide accurate estimates when the sample size of study participants within each area unit is sufficiently large, but it might not always be realistic to have large sample sizes of study participants when considering small geographical regions. Meanwhile, high dimensional socio-ecological data exist at the community level, providing an opportunity for model-based estimation by incorporating rich auxiliary information at the individual and area levels. Thus, it is critical …

Conditional Distance Correlation Test For Gene Expression Level, Dna Methylation Level And Copy Number, Shanshan Zhang

Graduate Theses and Dissertations

Over the past years, efforts have been devoted to the genome-wide analysis of genetic and epigenetic profiles to better understand the underlying biological mechanisms of complex diseases such as cancer. It is of great importance to unravel the complex dependence structure between biological factors, and many conditional dependence tests have been developed to meet this need. The traditional partial correlation method can only capture the linear partial correlation, but not the nonlinear correlation. To overcome this limitation, we propose to use the innovative conditional distance correlation (CDC), which measures the conditional dependence between random vectors and detect nonlinear relations. In …

Statistical Approaches Of Gene Set Analysis With Quantitative Trait Loci For High-Throughput Genomic Studies., Samarendra Das

Electronic Theses and Dissertations

Recently, gene set analysis has become the first choice for gaining insights into the underlying complex biology of diseases through high-throughput genomic studies, such as Microarrays, bulk RNA-Sequencing, single cell RNA-Sequencing, etc. It also reduces the complexity of statistical analysis and enhances the explanatory power of the obtained results. Further, the statistical structure and steps common to these approaches have not yet been comprehensively discussed, which limits their utility. Hence, a comprehensive overview of the available gene set analysis approaches used for different high-throughput genomic studies is provided. The analysis of gene sets is usually carried out based on …

Sensitivity Analysis For Incomplete Data And Causal Inference, Heng Chen

Statistical Science Theses and Dissertations

In this dissertation, we explore sensitivity analyses under three different types of incomplete data problems, including missing outcomes, missing outcomes and missing predictors, potential outcomes in \emph{Rubin causal model (RCM)}. The first sensitivity analysis is conducted for the \emph{missing completely at random (MCAR)} assumption in frequentist inference; the second one is conducted for the \emph{missing at random (MAR)} assumption in likelihood inference; the third one is conducted for one novel assumption, the ``sixth assumption'' proposed for the robustness of instrumental variable estimand in causal inference.

Accounting For The Uncertainty Due To Chemicals Below The Detection Limit In Mixture Analysis, Paul M. Hargarten

Theses and Dissertations

Humans are exposed to multiple chemicals every day. Epidemiological studies have shown that chemical mixtures are associated with cancers, allergies, neurodevelopmental disorders, and other adverse health effects. To assess these associations, investigators are increasingly using chemical mixture approaches like weighted quantile sum (WQS) regression. In these studies, the research objectives are to determine whether a mixture of correlated chemicals is associated with an adverse health outcome and to identify the important chemicals. However, as experimental equipment measures each exposure to a chemical-specific detection limit, the exposures are unknown between zero and the detection limit. Indeed, the number of exposures below …

Generalized Matrix Decomposition Regression: Estimation And Inference For Two-Way Structured Data, Yue Wang, Ali Shojaie, Tim Randolph, Jing Ma

UW Biostatistics Working Paper Series

Analysis of two-way structured data, i.e., data with structures among both variables and samples, is becoming increasingly common in ecology, biology and neuro-science. Classical dimension-reduction tools, such as the singular value decomposition (SVD), may perform poorly for two-way structured data. The generalized matrix decomposition (GMD, Allen et al., 2014) extends the SVD to two-way structured data and thus constructs singular vectors that account for both structures. While the GMD is a useful dimension-reduction tool for exploratory analysis of two-way structured data, it is unsupervised and cannot be used to assess the association between such data and an outcome of interest. …

Statistical Inference For Networks Of High-Dimensional Point Processes, Xu Wang, Mladen Kolar, Ali Shojaie

UW Biostatistics Working Paper Series

Fueled in part by recent applications in neuroscience, high-dimensional Hawkes process have become a popular tool for modeling the network of interactions among multivariate point process data. While evaluating the uncertainty of the network estimates is critical in scientific applications, existing methodological and theoretical work have only focused on estimation. To bridge this gap, this paper proposes a high-dimensional statistical inference procedure with theoretical guarantees for multivariate Hawkes process. Key to this inference procedure is a new concentration inequality on the first- and second-order statistics for integrated stochastic processes, which summarizes the entire history of the process. We apply this …

Unified Methods For Feature Selection In Large-Scale Genomic Studies With Censored Survival Outcomes, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

One of the major goals in large-scale genomic studies is to identify genes with a prognostic impact on time-to-event outcomes which provide insight into the disease's process. With rapid developments in high-throughput genomic technologies in the past two decades, the scientific community is able to monitor the expression levels of tens of thousands of genes and proteins resulting in enormous data sets where the number of genomic features is far greater than the number of subjects. Methods based on univariate Cox regression are often used to select genomic features related to survival outcome; however, the Cox model assumes proportional hazards …

Controlling For Confounding Via Propensity Score Methods Can Result In Biased Estimation Of The Conditional Auc: A Simulation Study, Hadiza I. Galadima, Donna K. Mcclish

Community & Environmental Health Faculty Publications

In the medical literature, there has been an increased interest in evaluating association between exposure and outcomes using nonrandomized observational studies. However, because assignments to exposure are not random in observational studies, comparisons of outcomes between exposed and nonexposed subjects must account for the effect of confounders. Propensity score methods have been widely used to control for confounding, when estimating exposure effect. Previous studies have shown that conditioning on the propensity score results in biased estimation of conditional odds ratio and hazard ratio. However, research is lacking on the performance of propensity score methods for covariate adjustment when estimating the …

Statistical Modeling Of Influenza-Like-Illness In Montana Using Spatial And Temporal Methods, Benjamin A. Stark

Graduate Student Theses, Dissertations, & Professional Papers

Studying air pollution and public health has been a historically important question in science. It has long been hypothesized that severe air pollution conditions lead to negative implications in basic human health. Primarily, areas thats are prone to severe degrees of human pollution are the focus of such studies. Such research relating to less populated areas are scarce, and this scarcity raises the question of how such pollution dynamics (human-made and natural) influence human health in more rural areas.

The aim of this study is to explore this hole in research; in particular we explore possible links between air pollution …

Evaluation Of Progress Towards The Unaids 90-90-90 Hiv Care Cascade: A Description Of Statistical Methods Used In An Interim Analysis Of The Intervention Communities In The Search Study, Laura Balzer, Joshua Schwab, Mark J. Van Der Laan, Maya L. Petersen

U.C. Berkeley Division of Biostatistics Working Paper Series

WHO guidelines call for universal antiretroviral treatment, and UNAIDS has set a global target to virally suppress most HIV-positive individuals. Accurate estimates of population-level coverage at each step of the HIV care cascade (testing, treatment, and viral suppression) are needed to assess the effectiveness of "test and treat" strategies implemented to achieve this goal. The data available to inform such estimates, however, are susceptible to informative missingness: the number of HIV-positive individuals in a population is unknown; individuals tested for HIV may not be representative of those whom a testing intervention fails to reach, and HIV-positive individuals with a viral …

Informational Index And Its Applications In High Dimensional Data, Qingcong Yuan

Theses and Dissertations--Statistics

We introduce a new class of measures for testing independence between two random vectors, which uses expected difference of conditional and marginal characteristic functions. By choosing a particular weight function in the class, we propose a new index for measuring independence and study its property. Two empirical versions are developed, their properties, asymptotics, connection with existing measures and applications are discussed. Implementation and Monte Carlo results are also presented.

We propose a two-stage sufficient variable selections method based on the new index to deal with large p small n data. The method does not require model specification and especially focuses …

Stochastic Optimization Of Adaptive Enrichment Designs For Two Subpopulations, Aaron Fisher, Michael Rosenblum

Johns Hopkins University, Dept. of Biostatistics Working Papers

An adaptive enrichment design is a randomized trial that allows enrollment criteria to be modified at interim analyses, based on a preset decision rule. When there is prior uncertainty regarding treatment effect heterogeneity, these trial designs can provide improved power for detecting treatment effects in subpopulations. We present a simulated annealing approach to search over the space of decision rules and other parameters for an adaptive enrichment design. The goal is to minimize the expected number enrolled or expected duration, while preserving the appropriate power and Type I error rate. We also explore the benefits of parallel computation in the …

Conditional Screening For Ultra-High Dimensional Covariates With Survival Outcomes, Hyokyoung Grace Hong, Jian Kang, Yi Li

The University of Michigan Department of Biostatistics Working Paper Series

Identifying important biomarkers that are predictive for cancer patients' prognosis is key in gaining better insights into the biological influences on the disease and has become a critical component of precision medicine. The emergence of large-scale biomedical survival studies, which typically involve excessive number of biomarkers, has brought high demand in designing efficient screening tools for selecting predictive biomarkers. The vast amount of biomarkers defies any existing variable selection methods via regularization. The recently developed variable screening methods, though powerful in many practical setting, fail to incorporate prior information on the importance of each biomarker and are less powerful in …

Models For Hsv Shedding Must Account For Two Levels Of Overdispersion, Amalia Magaret

UW Biostatistics Working Paper Series

We have frequently implemented crossover studies to evaluate new therapeutic interventions for genital herpes simplex virus infection. The outcome measured to assess the efficacy of interventions on herpes disease severity is the viral shedding rate, defined as the frequency of detection of HSV on the genital skin and mucosa. We performed a simulation study to ascertain whether our standard model, which we have used previously, was appropriately considering all the necessary features of the shedding data to provide correct inference. We simulated shedding data under our standard, validated assumptions and assessed the ability of 5 different models to reproduce the …

Aggregated Quantitative Multifactor Dimensionality Reduction, Rebecca E. Crouch

Theses and Dissertations--Statistics

We consider the problem of making predictions for quantitative phenotypes based on gene-to-gene interactions among selected Single Nucleotide Polymorphisms (SNPs). Previously, Quantitative Multifactor Dimensionality Reduction (QMDR) has been applied to detect gene-to-gene interactions associated with elevated quantitative phenotypes, by creating a dichotomous predictor from one interaction which has been deemed optimal. We propose an Aggregated Quantitative Multifactor Dimensionality Reduction (AQMDR), which exhaustively considers all k-way interactions among a set of SNPs and replaces the dichotomous predictor from QMDR with a continuous aggregated score. We evaluate this new AQMDR method in a series of simulations for two-way and three-way interactions, …

Inequality In Treatment Benefits: Can We Determine If A New Treatment Benefits The Many Or The Few?, Emily Huang, Ethan Fang, Daniel Hanley, Michael Rosenblum

Johns Hopkins University, Dept. of Biostatistics Working Papers

The primary analysis in many randomized controlled trials focuses on the average treatment effect and does not address whether treatment benefits are widespread or limited to a select few. This problem affects many disease areas, since it stems from how randomized trials, often the gold standard for evaluating treatments, are designed and analyzed. Our goal is to learn about the fraction who benefit from a treatment, based on randomized trial data. We consider the case where the outcome is ordinal, with binary outcomes as a special case. In general, the fraction who benefit is a non-identifiable parameter, and the best …

C-Learning: A New Classification Framework To Estimate Optimal Dynamic Treatment Regimes, Baqun Zhang, Min Zhang

The University of Michigan Department of Biostatistics Working Paper Series

Personalizing treatment to accommodate patient heterogeneity and the evolving nature of a disease over time has received considerable attention lately. A dynamic treatment regime is a set of decision rules, each corresponding to a decision point, that determine that next treatment based on each individual’s own available characteristics and treatment history up to that point. We show that identifying the optimal dynamic treatment regime can be recast as a sequential classification problem and is equivalent to sequentially minimizing a weighted expected misclassification error. This general classification perspective targets the exact goal of optimally individualizing treatments and is new and fundamentally …

Statistical Inference For The Mean Outcome Under A Possibly Non-Unique Optimal Treatment Strategy, Alexander R. Luedtke, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

We consider challenges that arise in the estimation of the value of an optimal individualized treatment strategy defined as the treatment rule that maximizes the population mean outcome, where the candidate treatment rules are restricted to depend on baseline covariates. We prove a necessary and sufficient condition for the pathwise differentiability of the optimal value, a key condition needed to develop a regular asymptotically linear (RAL) estimator of this parameter. The stated condition is slightly more general than the previous condition implied in the literature. We then describe an approach to obtain root-n rate confidence intervals for the optimal value …

Interadapt -- An Interactive Tool For Designing And Evaluating Randomized Trials With Adaptive Enrollment Criteria, Aaron Joel Fisher, Harris Jaffee, Michael Rosenblum

Johns Hopkins University, Dept. of Biostatistics Working Papers

The interAdapt R package is designed to be used by statisticians and clinical investigators to plan randomized trials. It can be used to determine if certain adaptive designs offer tangible benefits compared to standard designs, in the context of investigators’ specific trial goals and constraints. Specifically, interAdapt compares the performance of trial designs with adaptive enrollment criteria versus standard (non-adaptive) group sequential trial designs. Performance is compared in terms of power, expected trial duration, and expected sample size. Users can either work directly in the R console, or with a user-friendly shiny application that requires no programming experience. Several added …