Statistics and Probability Commons^™

Bayesian Designs For Two-Arm Clinical Trials With Time-To-Event Endpoints: Incorporating Historical Data Through Power Priors, Sara Hajraf H. Almutiri

Mathematics & Statistics ETDs

Bayesian methods provide a flexible framework for time-to-event analysis by incorporating prior information. The power prior offers a systematic way to borrow information from historical data. This approach is especially valuable in clinical research, where historical data can enhance inference in early-phase trials with limited sample sizes. This dissertation develops Bayesian approaches for two-arm survival studies using both closed-form and simulation-based methods. The closed-form inference is derived under exponential and Weibull survival models. Under the proportional hazards framework, the posterior is derived through a normal approximation to the log hazard ratio, allowing inference on the treatment effect when the variance …

Survival Patterns Among Adult And Pediatric Bone Cancer Patients, Ethan Estes

Mathematical Sciences Undergraduate Honors Theses

Recently noted, Huang et al. (2023), machine learning (ML) models, while offering great advantages over traditional statistical predictive modeling methods, are less explored in the analysis of survival and other similar time-to-event predictive data modeling. ML methods such as neural networks offer a great deal of promise but need to be further explored to investigate their comparative power in predicting survival outcomes. Focusing specifically on survival analysis in adult and pediatric bone cancer patients, traditional methods, like shown in Emmert-Streib and Dehmer (2019), will be shown with machine learning models using methods in Hothorn, Hornik, and Zeileis (2006). In this …

A Note On Sufficient Dimension Folding For Regression Mean Function With Categorical Predictors, Bilin Zeng, Akim Adekpedjou, Xuerong Meggie Wen

Mathematics and Statistics Faculty Research & Creative Works

Multi-dimensional arrays are referred to as tensors. Tensor-valued predictors are commonly encountered in modern biomedical applications, such as electroencephalogram (EEG), magnetic resonance imaging (MRI), functional MRI (fMRI), diffusion-weighted MRI, and longitudinal health data. In survival analysis, it is both important and challenging to integrate clinically relevant information, such as gender, age, and disease state along with medical imaging tensor data or longitudinal health data to predict disease outcomes. Most existing higher-order sufficient dimension reduction regressions for matrix- or array-valued data focus solely on tensor data, often neglecting established clinical covariates that are readily available and known to have predictive value. …

Novel R Shiny Tool For Survival Analysis With Time-Varying Covariate In Oncology Studies: Overcoming Biases And Enhancing Collaboration, Yimei Li, Yang Qiao, Fei Gao, Jordan Gauthier, Qiang Ed Zhang, Jenna Voutsinas, Wendy Leisenring, Ted Gooley, Corinne Summers, Alexandre Hirayama, Cameron Turtle, Rebecca Gardner, Jarcy Zee, Qian Vicky Wu

Wills Eye Hospital Papers

PURPOSE: Our study is motivated by evaluating the role of hematopoietic cell transplantation (HCT) after chimeric antigen receptor T-cell (CAR-T) therapy for ALL, a debated topic. Because patients may receive HCT at different times after CAR-T infusion or never, HCT post-CAR-T should be considered as a time-varying covariate (TVC).

METHODS: Standard Cox models and Kaplan-Meier (KM) curves (naïve method) assume that TVC status is known and fixed at baseline, which can yield biased estimates. Landmark analysis is a popular alternative but depends on a chosen landmark time. Time-dependent (TD) Cox model is better suited for TVC although visualizing survival curves …

Two Topics In Survival Analysis: Restricted Distance Covariance Test For Non-Proportional Hazard And A New Estimation For Dropout Rate, Ruizhe Yin

Graduate Theses and Dissertations

When treatment effects change over time, standard statistical methods, such as the log-rank test and the Cox proportional hazards model, may give misleading results. This dissertation presents the restricted distance covariance (rdcov) test, a nonparametric method that compares survival curves between groups within a chosen study period [0, τ] using right censored data. The statistic measures the dependence between pre-specified group labels and survival times using pairwise distances from Kaplan-Meier estimates. Our method does not rely on the proportional hazards assumption, and it equals zero only when survival functions are identical across groups. Thus, this test can be applied to …

Neighborhood Socioeconomic Status And Overall Survival Among Children With Acute Lymphoblastic Leukemia, Anna Hoppmann, Debroah M. Hurley, Stuart Cramer, Monique J. Brown Ph.D., Mph

Faculty Publications

A disadvantaged neighborhood, as represented by area-level socioeconomic status (SES) has been associated with adverse outcomes among children with acute lymphoblastic leukemia (ALL) in the US, but the duration of impact after ALL diagnosis is not well understood. This retrospective cohort study utilized the National Cancer Database (NCDB) to examine the impact of area-level SES on overall survival among children with ALL. Median income and education quartiles based on residential zip code were used to create a composite area-level SES variable. Individual-level variables included age, sex, race, year of diagnosis, primary payer, distance to care, rurality, time to treatment, and …

Methods And Applications For Bayesian Semiparametric Survival Analysis, Zile Zhao

Theses and Dissertations

Survival analysis is a cornerstone of biomedical and clinical research and plays an important role in fields as diverse as engineering, actuarial science, and sociology. In this dissertation, we develop new semiparametric Bayesian methodology for three problems from survival analysis: 1) adjustment for treatment crossover in randomized controlled trials (RCTs), 2) multilevel modeling of clustered survival outcomes when the cluster size is also informative, and 3) divide-and-conquer Bayesian inference for massive survival data. Our methods are semiparametric in the sense that we assume the covariates have a linear effect with regard to the log-hazard or the log- survival time; however, …

Innovative Methods For The Design And Analysis Of Phase Ii Clinical Trials, Feng Tian

Dissertations and Theses (Open Access)

Drug development has become increasingly time-consuming, costly, and risky in recent years. There is significant potential for improving clinical trial designs, particularly for phase II trials, which play a critical role in the drug development process. Innovative methods are especially necessary for addressing key challenges in phase II trials in terms of dose-ranging study, patient population selection, and decentralized clinical trials (DCTs). This dissertation presents a comprehensive set of methodologies that address these critical issues with three projects. The first project introduces a Bayesian adaptive dose-ranging design that integrates both efficacy and toxicity data to evaluate each dose comprehensively. The …

Highest Risk Density Region For The Communication Of The Impact Of A Treatment Covariate On The Time-To-Event Distribution, Giacomo Biganzoli, Giuseppe Marano Phd, Patrizia Boracchi Phd

COBRA Preprint Series

Analysis of time-to-event (TTE) data is central to clinical research, yet conventional summary measures like the hazard ratio (HR) and restricted mean survival time (RMST) present significant challenges. The HR is often misinterpreted, and its validity depends on the frequently violated proportional hazards assumption, while the RMST is highly sensitive to the choice of time horizon. This paper introduces two novel, assumption-free estimands to address these limitations: the Highest Risk Density Region (HRDR) and the Highest Net Risk Difference Region (HNRDR).

The HRDR identifies the narrowest time interval containing a pre-specified probability mass of events, directly answering the clinical question: …

Dynamic Prediction Of Disease Progression With Longitudinal Data, Wenhao Li

Dissertations and Theses (Open Access)

Dynamic prediction plays a pivotal role in clinical research, especially when forecasting time-to-event outcomes based on evolving longitudinal data. This process often leverages the integration of longitudinal and time-to-event data through joint modeling, a prevalent technique. Alongside joint modeling, landmark modeling stands as another key approach in the realm of longitudinal studies. These methodologies are instrumental in dynamically predicting clinical events by utilizing predictor variables measured over time, up until the moment predictions are made. Within this framework, Chapter 2 addresses the challenge of comparing joint modeling and landmark modeling for dynamic prediction in longitudinal studies, introducing a novel algorithm …

Mathematical Modeling Of Tumor Response Dynamics To Predict Progression-Free Survival In Patients With Recurrent High-Grade Glioma, Daniel James Glazar

USF Tampa Graduate Theses and Dissertations

In this dissertation, I aim to develop a mathematical model describing tumor volume response dynamics to perform individual dynamic predictions of progression-free survival (PFS) on patients with recurrent high-grade glioma (rHGG).

Patients with rHGG have a dismal prognosis with median overall survival (OS) of <12 months and median PFS of <7 months. However, there is a wide heterogeneity in treatment responses. Therefore, to aid clinicians with making decisions to alter therapeutic protocol, I would like to predict patient-specific PFS.

To perform individual dynamic predictions, I employ the Claret tumor growth inhibition (TGI) model. I further develop this model by coupling it with two different survival models. Inter-patient heterogeneity is also taken into account through mixed effects, including covariate effects. Model PFS predictions were evaluated using receiver operating characteristic (ROC) curve analysis as well as Brier …

Integrating Machine Learning With Cure Models And Associated Inference, Wisdom Aselisewine

Mathematics Dissertations - Archive

Recent advancements in medical treatments have significantly enhanced the rates of recovery for numerous chronic illnesses. This progress has sparked growing interest in developing suitable statistical models capable of handling survival data that includes substantial cure fractions. The mixture cure model finds extensive application in analyzing survival data when there exists a cured subgroup. Standard logistic regression-based approaches for modeling the incidence part of the mixture cure model may suffer from poor predictive accuracy, especially in the presence of high dimensional covariates and/or non-linear covariate effects. To overcome this limitation, we propose the integration of distinct machine learning algorithms with …

Addressing The Analytical And Computational Challenges Using Machine Learning In Biomedical Research, Yizhuo Wang

Dissertations and Theses (Open Access)

In the contemporary healthcare field, professionals are confronted with an ever-growing volume of clinical data stored in electronic health records, alongside the genomic data stemming from laboratory experiments. As a response to this deluge of data, the application of machine learning (ML) techniques is gaining popularity since ML techniques have demonstrated an exceptional proficiency in processing big data and deciphering complex nonlinear patterns that are intrinsic to biomedical research.

My research leverages ML's capabilities to address the computational challenges spanning diverse areas, including adaptive clinical trial designs, survival analysis, and high-dimensional genetic data analysis. Specifically, Chapter 2 focused on the …

Detecting Gene-Gene Or Gene Environment Interactions In Association With Complex Disease Outcomes, Taiwo Adetunji Famuyiwa

Theses and Dissertations

Identifying gene–gene and gene–environment interaction is complicated and gainsaying most especially because of high multifactor dimensions involve in the analysis of such combination discrediting the functionality of parametric statistical method like Logistic Regression. [22] developed a multi-factor-dimensionality reduction (MDR) method for detecting and characterizing high-order gene-gene and gene-environment interactions in case-control and discordant-sib-pair studies with relatively small samples, which is inspired by the combinatorial partitioning method of [18]. [16] proposed Generalized MDR (GMDR) framework based on the score of a generalized linear model which allows adjustment of covariates, provides a unified framework for handling both dichotomous and quantitative phenotypes. However, …

Examining Failures Of Kc-135 Boom Assemblies Using Survival Analysis, Benjamin D. Miller

Theses and Dissertations

The purposes of this study are to confirm the applicability of survival analysis for predicting recurrent failures of a component of a military aircraft and to provide practical insights to maintenance managers and mission planners. The results of this study also can help the United States Department of Defense improve the CBM+ program. This study was able to predict recurrent failures of the component using Nelson-Aalen cumulative estimates. In addition, this study used a Cox proportional hazards regression model with shared frailty for measuring the effect of covariates on recurrent failures and unidentified heterogeneity in the model, which warranted future …

Novel Feature Evaluation In Ultra-High Dimensional Right-Censored Data, With Applications To Head And Neck Cancer, Atika Farzana Urmi

Graduate Research Posters

Background: Head and neck cancer is the 6th most common cancer worldwide with an expected 1.08 million new cases each year. Such cancer data are ultra-high dimensional with thousands of clinical features and gene expressions, making it challenging for the traditional analytical tools to extract the potential biomarker for the cancer survival and control false discoveries. In addition, presence of heavy censoring can affect the screening procedures based on Kaplan-Meier (K-M) survival estimates.

Aim: To propose a model free, ultra-high dimensional feature screening method with two-dimensional survival outcome allowing false discovery rate (FDR) control.

Method: 516 primary tumor patients with …

Prediction Of Rapid Early Progression And Survival Risk With Pre-Radiation Mri In Who Grade 4 Glioma Patients, Walia Farzana, Mustafa M. Basree, Norou Diawara, Zeina Shboul, Sagel Dubey, Marie M. Lockheart, Mohamed Hamza, Joshua D. Palmer, Khan Iftekharuddin

Electrical & Computer Engineering Faculty Publications

Rapid early progression (REP) has been defined as increased nodular enhancement at the border of the resection cavity, the appearance of new lesions outside the resection cavity, or increased enhancement of the residual disease after surgery and before radiation. Patients with REP have worse survival compared to patients without REP (non-REP). Therefore, a reliable method for differentiating REP from non-REP is hypothesized to assist in personlized treatment planning. A potential approach is to use the radiomics and fractal texture features extracted from brain tumors to characterize morphological and physiological properties. We propose a random sampling-based ensemble classification model. The proposed …

Television Viewing Time And All-Cause Mortality: Interactions With Bmi, Physical Activity, Smoking, And Dietary Factors, Christopher T. Swain, Julie K. Bassett, Allison M. Hodge, David W. Dunstan, Neville Owen, Yi Yang, Harindra Jayasekara, James R. Hébert Scd, Nitin Shivappa Mbbs, Mph, Ph.D., Robert J. Macinnis, Roger L. Milne, Dallas R. English, Brigid M. Lynch

Faculty Publications

Background Higher levels of time spent sitting (sedentary behavior) contribute to adverse health outcomes, including earlier death. This effect may be modified by other lifestyle factors. We examined the association of television viewing (TV), a common leisure-time sedentary behavior, with all-cause mortality, and whether this is modified by body mass index (BMI), physical activity, smoking, alcohol intake, soft drink consumption, or diet-associated inflammation. Methods Using data from participants in the Melbourne Collaborative Cohort Study, flexible parametric survival models assessed the time-dependent association of self-reported TV time (three categories: < 2 h/day, 2-3 h/day, > 3 h/day) with all-cause mortality. Interaction terms were fitted to test whether …

Determinants Of Covid-19 Vaccinations Among A State-Wide Year-Long Surveillance Initiative In A Conservative Southern State, Lídia Gual-Gonzalez, Maggie S.J. Mccarter, Kyndall Dye-Braumuller, Stella Self, Connor H. Ross, Chloe Rodriguez-Ramos, Virginie G. Daguise, Melissa Nolan Ph.D., Mph

Faculty Publications

By the end of 2021, the COVID-19 pandemic resulted in over 54 million cases and more than 800,000 deaths in the United States, and over 350 million cases and more than 5 million deaths worldwide. The uniqueness and gravity of this pandemic have been reflected in the public health guidelines poorly received by a growing subset of the United States population. These poorly received guidelines, including vaccine receipt, are a highly complex psychosocial issue, and have impacted the successful prevention of disease spread. Given the intricate nature of this important barrier, any single statistical analysis methodologically fails to address all …

Predicting Tf33-Pw-100a Engine Failures Due To Oil Issues Using Survival Analyses, Anna M. Davis

Theses and Dissertations

In 2007, the Office of the Assistant Secretary of Defense for Sustainment pushed for the need to transition to a Condition Based Maintenance Plus (CBM ) initiative for weapon systems in the U.S. Department of Defense. The CBM initiative can help increase aircraft availability (AA) for the United States Air Force. There are many reasons where AA can be affected but one such issue is engine availability primarily due to oil issues. Within the CBM perspective, this study examines the risk of a jet engine failure due to an oil issue and attempts to predict an engines time until next …

Examining Failures Of Kc-135s Using Survival Analysis, Vanessa I. R. Unseth

Theses and Dissertations

The United States Air Force manages an inventory of 396 KC-135 Stratotanker aircraft. With mission capability rates falling and total non-mission capability supply rates increasing, it is necessary to take a deeper look at recurrent failures. The study applies non-parametric and semi-parametric survival models to a dataset retrieved from LIMS-EV to look at the duration(s) until failure for the KC-135. Results of non-parametric models show cumulative failure rates increase as sorties or flight hours increase. In addition, semi-parametric models or Cox proportional hazards models with frailty confirm that locations or air bases are not associated with recurrent failures.

Multivariate Statistical Modeling For Radio-Genomics Study, Tiantian Zeng

Theses and Dissertations--Statistics

Radiogenomics is a new direction in cancer research that focuses on the associations among radiomics, genomics and clinical outcome. Currently, the major challenge for Radiogenomics lies in the effective integration of genomics and imaging data for promising clinical outcome prediction. Herein, we propose a multivariate joint model that can integrate imaging and genomic data for better predicting the clinical outcome. Specifically, we jointly consider two multivariate group lasso models, one regresses imaging features on genomic features, and the other regresses patient’s clinical outcome on genomic features. An L1 penalty term is introduced for each variable, and weight in the penalty …

Dependent Censoring In Survival Analysis, Zhongcheng Lin

Dissertations

This dissertation mainly consists of two parts. In the first part, some properties of bivariate Archimedean Copulas formed by two time-to-event random variables are discussed under the setting of left censoring, where these two variables are subject to one left-censored independent variable respectively. Some distributional results for their joint cdf under different censoring patterns are presented. Those results are expected to be useful in both model fitting and checking procedures for Archimedean copula models with bivariate left-censored data. As an application of the theoretical results that are obtained, a moment estimator of the dependence parameter in Archimedean copula models is …

An Examination Of Civilian Retention In The United States Air Force, William F. Wilson

Theses and Dissertations

The backbone of the United States Air Force is undoubtedly the large civilian workforce that supplements the great work that is accomplished. Many research studies have been conducted on officer and enlisted personnel to ensure that the career fields are properly developed and managed to meet the ever growing demands of the military's varied missions, but no recent studies have focused on the civilian workforce. Striking a balance between new and experienced employees is paramount to success given the ever-changing economic and political landscapes where we find ourselves. The first part of the research uses logistic regression to determine the …

Optimizing Critical Values And Combining Axes For Multi-Axial Neck Injury Criteria, Ethan J. Gaston

Theses and Dissertations

The Air Force employs ejection seats in its high-performance aircraft. While these systems are intended to ensure aircrew safety, the ejection process subjects the aircrew to potentially injurious forces. System validation includes evaluation of forces against a standard which is linked to the probability of injury. The Muti-Axial Neck Injury Criteria (MANIC) was developed to account for forces in all six degrees of freedom. Unfortunately, the MANIC is applied to each of the three linear input directions separately and applies different criterion values for each direction. These three separate criteria create a lack of clarity regarding acceptable neck loading, leading …

Inference And Estimation In Change Point Models For Censored Data, Kristine Gierz

Mathematics & Statistics Theses & Dissertations

In general, the change point problem considers inference of a change in distribution for a set of time-ordered observations. This has applications in a large variety of fields and can also apply to survival data. With improvements to medical diagnoses and treatments, incidences and mortality rates have changed. However, the most commonly used analysis methods do not account for such distributional changes. In survival analysis, change point problems can concern a shift in a distribution for a set of time-ordered observations, potentially under censoring or truncation.

In this dissertation, we first propose a sequential testing approach for detecting multiple change …

Robustness Of Semi-Parametric Survival Model: Simulation Studies And Application To Clinical Data, Isaac Nwi-Mozu

Electronic Theses and Dissertations

An efficient way of analyzing survival clinical data such as cancer data is a great concern to health experts. In this study, we investigate and propose an efficient way of handling survival clinical data. Simulation studies were conducted to compare performances of various forms of survival model techniques using an R package ``survsim". Models performance was conducted with varying sample sizes as small ($n5000$). For small and mild samples, the performance of the semi-parametric outperform or approximate the performance of the parametric model. However, for large samples, the parametric model outperforms the semi-parametric model. We compared the effectiveness and reliability …

Maximum Likelihood Estimation For The Generalized Pareto Distribution And Goodness-Of-Fit Test With Censored Data, Minh H. Pham, Chris Tsokos, Bong-Jin Choi

Journal of Modern Applied Statistical Methods

The generalized Pareto distribution (GPD) is a flexible parametric model commonly used in financial modeling. Maximum likelihood estimation (MLE) of the GPD was proposed by Grimshaw (1993). Maximum likelihood estimation of the GPD for censored data is developed, and a goodness-of-fit test is constructed to verify an MLE algorithm in R and to support the model-validation step. The algorithms were composed in R. Grimshaw’s algorithm outperforms functions available in the R package ‘gPdtest’. A simulation study showed the MLE method for censored data and the goodness-of-fit test are both reliable.

General Approach Of Causal Mediation Analysis With Causally Ordered Multiple Mediators And Survival Outcome, An-Shun Tai, Pei-Hsuan Lin, Yen-Tsung Huang, Sheng-Hsuan Lin

Harvard University Biostatistics Working Paper Series

Causal mediation analysis with multiple mediators (causal multi-mediation analysis) is critical in understanding why an intervention works, especially in medical research. Deriving the path-specific effects (PSEs) of exposure on the outcome through a certain set of mediators can detail the causal mechanism of interest. However, the existing models of causal multi-mediation analysis are usually restricted to partial decomposition, which can only evaluate the cumulative effect of several paths. Moreover, the general form of PSEs for an arbitrary number of mediators has not been proposed. In this study, we provide a generalized definition of PSE for partial decomposition (partPSE) and for …

A Statistical Analysis And Machine Learning Of Genomic Data, Jongyun Jung

All Graduate Theses, Dissertations, and Other Capstone Projects

Machine learning enables a computer to learn a relationship between two assumingly related types of information. One type of information could thus be used to predict any lack of informaion in the other using the learned relationship. During the last decades, it has become cheaper to collect biological information, which has resulted in increasingly large amounts of data. Biological information such as DNA is currently analyzed by a variety of tools. Although machine learning has already been used in various projects, a flexible tool for analyzing generic biological challenges has not yet been made. The recent advancements in the DNA …