Survival Analysis Commons^™

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 …

Statistical Methods For Joint Outcome Modeling And Dynamic Assessment Of Recurrent Events, Zifang Kong

Statistical Science Theses and Dissertations

Recurrent event data frequently arise in clinical studies where individuals experience repeated, possibly related, events over time. These data are often accompanied by sparse and irregular longitudinal measurements, creating challenges for traditional joint modeling approaches that struggle to account for time-dependent associations and within-subject correlations. We propose FRAILTY (Functional Regression with AutoRegressIve fraiLTY), a novel two-step framework that integrates functional principal component analysis (PACE) with a dynamic frailty model featuring autoregressive structure. FRAILTY accommodates both scalar and functional predictors and captures within-subject dependence across recurrent events. To further extend its utility, we develop a multivariate joint modeling framework that simultaneously …

Evaluating Alpha Spending Functions Applied To Observational Time-To-Event Analysis, Moses Torgbenu

Electronic Theses and Dissertations

This thesis explores the theoretical foundation of the alpha spending approach and extends its application beyond the conventional setting of randomized controlled trials (RCTs) to observational studies with time to event analyses. In these less structured environments, key design parameters such as the total number of events are often unknown, posing challenges for the standard implementation of sequential analysis methods.

Through simulation studies, this research delivers several important contributions. First, it presents a modified approach that uses calendar time to define the timing of interim analyses while relying on event-based information to estimate the correlation among test statistics. This adjustment …

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 …

Predicting Capture And Survival Probabilities Of The Arizona Tiger Salamander: A Comparison Of Capture-Recapture Models, Brittney Nelson

Scholars Week

Capture-recapture models are essential tools for estimating population dynamics in ecological studies. A fundamental component of these models is the capture history matrix, which records individual detection over time and serves as the basis for estimating survival and capture probabilities. This presentation explores three statistical approaches to these estimations: the Cormack-Jolly-Seber (CJS) model, the Hidden Markov Model (HMM) for CJS, and the Bayesian CJS model. The CJS model provides a likelihood-based framework for estimation, and the HMM CJS incorporates latent states into the model to account for uncertainty in detection. The Bayesian CJS extends this same analysis by integrating prior …

The Impact Of “Multiple Looks” When Performing Survival Analysis, Quentin Eloise

Electronic Theses and Dissertations

Survival analysis is a critical statistical method in healthcare to assess patient treatment effects and disease progression. Another critical area of statistical methodology in health care is the practice of adaptive designs. Adaptive designs allow for interim analyses to take place during a study and various decisions and actions can take place more ethically. This is beneficial for studies that take multiple years to complete and allows administrators and healthcare providers to make sound decisions as early as possible. A challenging aspect of adaptive designs is that the number of interim analyses is known in advance which is applicable in …

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 …

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 …

Evaluating Novel Approaches For Improving Anadromous Fish Passage In Coastal Rivers, Aaron Bunch

All Dissertations

Few of the world's rivers remain free-flowing for over 1000 km, significantly impacting anadromous fish populations due to dam-induced habitat fragmentation. Three partial migration barriers (low-head dams) on North Carolina's Cape Fear River (USA)—lock and dam 1 (LD1), lock and dam 2 (LD2), and lock and dam 3 (LD3)—impact American shad Alosa sapidissima, Atlantic sturgeon Acipenser oxyrinchus oxyrinchus, and striped bass Morone saxatilis populations. Mitigation strategies to pass fish upstream have included conservation locking, nature-like fishway construction, and environmental flows (e-flows). This study introduced a novel e-flow (dam submergence flow), tested acoustic double-tagging techniques for tracking American …

Applications Of Causal Inference Methods For The Estimation Of Effects Of Bone Marrow Transplant And Prescription Drugs On Survival Of Aplastic Anemia Patients, Yesha M. Patel

Computational and Data Sciences (PhD) Dissertations

This dissertation provides an in-depth exploration into the treatment effectiveness for aplastic anemia using causal inference methods, structured around three pivotal research papers. Each paper contributes to a nuanced understanding of treatment impacts, specifically focusing on bone marrow transplantation (BMT) and prescription drugs, and the identification of optimal treatment strategies.

The first paper, "Causal Inference Analysis for Assessing the Effect of Bone Marrow Transplantation on the One-Year Survival of Adult and Pediatric Aplastic Anemia Patients," sets the foundation. It examines the short-term effectiveness of BMT in both adult and pediatric patients, providing crucial insights into how this treatment affects survival …

Causal Inference For The Effect Of Continuous Treatment On Time-To-Event Outcomes And Mediation Analysis On Health Disparities In Observational Studies., Triparna Poddar

Electronic Theses and Dissertations

The dissertation comprises two projects related to causal inference based on observational data. In healthcare research, where abundant observational data such as claims data and electronic records are available, researchers often aim to study the treatment effect and the pathway of that effect. However, estimating treatment effects in observational data presents challenges due to confounding factors. The first project focuses on estimating continuous treatment effects for survival outcomes, while the second concentrates on mediation analysis, allowing the exploration of the pathway of the causal effect. Both projects involve addressing confounding variables. In the first project, I investigate estimation of the …

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 …

Striving For Appropriate Antibiotic Use: A Biomarker Initiative, And Outcomes Associated With Azithromycin Exposure, Amanda Gusovsky

Theses and Dissertations--Pharmacy

The introduction of antibiotics into clinical practice is considered the greatest medical breakthrough of the 20^thcentury. However, the use of antibiotics can contribute to the development of resistance. In the United States (U.S.), approximately 2.8 million people are infected with antibiotic-resistant bacteria each year, and more than 35,000 people die as a result. Moreover, some antibiotics are known to cause cardiac side effects including QT prolongation, hypotension, and ventricular arrythmias. The U.S. Centers for Disease Control and Prevention (CDC) defines appropriate antibiotic use as the effort to use “the right antibiotic, at the right dose, for the right …

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 …

Regression Modeling Of Complex Survival Data Based On Pseudo-Observations, Rong Rong

Statistical Science Theses and Dissertations

The restricted mean survival time (RMST) is a clinically meaningful summary measure in studies with survival outcomes. Statistical methods have been developed for regression analysis of RMST to investigate impacts of covariates on RMST, which is a useful alternative to the Cox regression analysis. However, existing methods for regression modeling of RMST are not applicable to left-truncated right-censored data that arise frequently in prevalent cohort studies, for which the sampling bias due to left truncation and informative censoring induced by the prevalent sampling scheme must be properly addressed. Meanwhile, statistical methods have been developed for regression modeling of the cumulative …

Infrastructure Development For Personalized Risk Prediction To Reduce Cardiovascular Disease In Childhood Cancer Survivors, Suman Shrestha

Dissertations and Theses (Open Access)

Although childhood cancer survivors have lengthy life expectancies, they run the risk of experiencing long-term health issues as a result of their treatment. The most frequent non-cancerous cause of morbidity and mortality for these survivors is cardiac disease. Radiation therapy (RT) has been linked in numerous cohort studies to a higher chance of developing a late cardiac disease in these survivors, and this risk rises with higher mean heart doses and increased RT exposure to larger cardiac volumes. Since, the heart is a heterogeneous organ made up of several distinct substructures, RT dose received by the entire heart does not …

Statistical Methods For Personalized Treatment Selection And Survival Data Analysis Based On Observational Data With High-Dimensional Covariates., Don Ramesh Dinendra Sudaraka Tholkage

Electronic Theses and Dissertations

Due to the wide availability of functional data from multiple disciplines, the studies of functional data analysis have become popular in the recent literature. However, the related development in censored survival data has been relatively sparse. In Chapter 2, we consider the problem of analyzing time-to-event data in the presence of functional predictors. We develop a conditional generalized Kaplan Meier (KM) estimator that incorporates functional predictors using kernel weights and rigorously establishes its asymptotic properties. In addition, we propose to select the optimal bandwidth based on a time-dependent Brier score. We then carry out extensive numerical studies to examine the …

Factors Affecting Time To Recovery: A Covid-19 Survival Analysis, Fernanda Montoya

Honors Capstones

This project is focused on the recovery rates of patients diagnosed with COVID-19 after different clinical trial drug treatments. Data for the clinical trial studied was obtained from the National Institute of Allergy and Infectious Diseases for the primary purpose of a survival analysis on patient time to recovery under a placebo and therapeutic drug treatment. Specifically, patients in this clinical trial were randomly selected to receive remdesivir, an antiviral drug, in combination with a placebo or baricitinib, a janus kinase inhibitor drug. Cox PH models were used to identify how the different treatment drugs affect time to recovery and …

Approximate Likelihood Based Estimations For Joint Models With Intractable Likelihoods, Karl Stessy M. Bisselou

Theses & Dissertations

This dissertation focuses on the development of approximation approaches for the joint modeling (JM) of repeated measures data and time-to-event data in the presence of analytically or numerically intractable likelihoods. Current likelihood-based inferences for JMs show several limitations including (i) intractability of integrals during marginal likelihood derivations due to the complexity in computations, and (ii) the large number of nuisance parameters (unobserved) posing a problem with convergence. The h-likelihood (HL) and synthetic likelihood (SL) are two computationally efficient estimation approaches that overcome these challenges.

In the presence of extremely high censoring rates, the HL can produce bias parameter estimates. We …

Extension Of The Two-Step Approach For Informative Dropout In Survival Analysis, Cristina Murray-Krezan

Mathematics & Statistics ETDs

Chronic kidney disease (CKD) in children is known to result in poor growth and quality of life, and frequently results in kidney failure. The Chronic Kidney Disease in Children study (CKiD) is a prospective cohort study enrolling children ages 1 to 16 to assess health outcomes in children with CKD including the effects of declining glomerular filtration rate and the resulting consequences of growth failure on morbidity. Quantification of the magnitude of the risk for decreased kidney function and, ultimately, failure has been achieved through a variety of studies, often including cohort studies such as the CKiD study. Longitudinal studies …

Sars-Cov-2 Pandemic Analytical Overview With Machine Learning Predictability, Anthony Tanaydin, Jingchen Liang, Daniel W. Engels

SMU Data Science Review

Understanding diagnostic tests and examining important features of novel coronavirus (COVID-19) infection are essential steps for controlling the current pandemic of 2020. In this paper, we study the relationship between clinical diagnosis and analytical features of patient blood panels from the US, Mexico, and Brazil. Our analysis confirms that among adults, the risk of severe illness from COVID-19 increases with pre-existing conditions such as diabetes and immunosuppression. Although more than eight months into pandemic, more data have become available to indicate that more young adults were getting infected. In addition, we expand on the definition of COVID-19 test and discuss …

Innovative Statistical Models In Cancer Immunotherapy Trial Design, Jing Wei

Theses and Dissertations--Statistics

A challenge arising in cancer immunotherapy trial design is the presence of non-proportional hazards (NPH) patterns in survival curves. We considered three different NPH patterns caused by delayed treatment effect, cure rate and responder rate of treatment group in this dissertation. These three NPH patterns would violate the proportional hazard model assumption and ignoring any of them in an immunotherapy trial design will result in substantial loss of statistical power.

In this dissertation, four models to deal with NPH patterns are discussed. First, a piecewise proportional hazards model is proposed to incorporate delayed treatment effect into the trial design consideration. …

Analyzing Electronic Health Records With Time-To-Event Endpoints: Propensity Scores And Semiparametric Approaches, Jonathan W. Yu

Theses and Dissertations

For analyzing large electronic health records (EHR) with time-to-event endpoints, such as in kidney transplantation, a major challenge is to provide an accurate risk analyses, while accounting for a multitude of epidemiological and statistical complexities. Motivated by a right-censored kidney transplantation EHR dataset derived from the United Network of Organ Sharing (UNOS), this dissertation, through a culmination of two interrelated yet distinctly different projects, focuses on developments of novel statistical procedures and methodologies to address some pressing issues arising in EHR-based research. In the first project, we aim to decouple the causal effects of treatments (here, studying subgroups, such as …

Estimation Of The Treatment Effect With Bayesian Adjustment For Covariates, Li Xu

Theses and Dissertations--Statistics

The Bayesian adjustment for confounding (BAC) is a Bayesian model averaging method to select and adjust for confounding factors when evaluating the average causal effect of an exposure on a certain outcome. We extend the BAC method to time-to-event outcomes. Specifically, the posterior distribution of the exposure effect on a time-to-event outcome is calculated as a weighted average of posterior distributions from a number of candidate proportional hazards models, weighing each model by its ability to adjust for confounding factors. The Bayesian Information Criterion based on the partial likelihood is used to compare different models and approximate the Bayes factor. …

Effects Of Perioperative Hyperglycemia In Patients With Diabetes Compared To Patients Without Diabetes: A Retrospective Study Of Treatment And Outcomes, Matthew Anderson

Capstone Experience: Master of Public Health

The main goal of this project was to examine the differences in perioperative hyperglycemia treatment received by patients with a diagnosis of diabetes mellitus (DM) and patients without a diagnosis of diabetes (NDM); and how these treatment differences can affect the length of hospital stay. Studies have revealed that, when comparing DM and NDM patients with the same degree of perioperative hyperglycemia, NDM patients suffer worse outcomes. It has been suggested in previous research that this may be because NDM patients receive treatment that does not measure up to the standard of care treatment that DM patients receive. In 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 …

Variable Selection In Accelerated Failure Time (Aft) Frailty Models: An Application Of Penalized Quasi-Likelihood, Sarbesh R. Pandeya

College of Graduate Studies: Theses & Dissertations

Variable selection is one of the standard ways of selecting models in large scale datasets. It has applications in many fields of research study, especially in large multi-center clinical trials. One of the prominent methods in variable selection is the penalized likelihood, which is both consistent and efficient. However, the penalized selection is significantly challenging under the influence of random (frailty) covariates. It is even more complicated when there is involvement of censoring as it may not have a closed-form solution for the marginal log-likelihood. Therefore, we applied the penalized quasi-likelihood (PQL) approach that approximates the solution for such a …

Methods For Evaluating Dropout Attrition In Survey Data, Camille J. Hochheimer

Theses and Dissertations

As researchers increasingly use web-based surveys, the ease of dropping out in the online setting is a growing issue in ensuring data quality. One theory is that dropout or attrition occurs in phases that can be generalized to phases of high dropout and phases of stable use. In order to detect these phases, several methods are explored. First, existing methods and user-specified thresholds are applied to survey data where significant changes in the dropout rate between two questions is interpreted as the start or end of a high dropout phase. Next, survey dropout is considered as a time-to-event outcome and …

Comparison Of Survival Curves Between Cox Proportional Hazards, Random Forests, And Conditional Inference Forests In Survival Analysis, Brandon Weathers

All Graduate Plan B and other Reports, Spring 1920 to Spring 2023

Survival analysis methods are a mainstay of the biomedical fields but are finding increasing use in other disciplines including finance and engineering. A widely used tool in survival analysis is the Cox proportional hazards regression model. For this model, all the predicted survivor curves have the same basic shape, which may not be a good approximation to reality. In contrast the Random Survival Forests does not make the proportional hazards assumption and has the flexibility to model survivor curves that are of quite different shapes for different groups of subjects. We applied both techniques to a number of publicly available …

Statistical Methods For Two Problems In Cancer Research: Analysis Of Rna-Seq Data From Archival Samples And Characterization Of Onset Of Multiple Primary Cancers, Jialu Li

Dissertations and Theses (Open Access)

My dissertation is focused on quantitative methodology development and application for two important topics in translational and clinical cancer research.

The first topic was motivated by the challenge of applying transcriptome sequencing (RNA-seq) to formalin-fixation and paraffin-embedding (FFPE) tumor samples for reliable diagnostic development. We designed a biospecimen study to directly compare gene expression results from different protocols to prepare libraries for RNA-seq from human breast cancer tissues, with randomization to fresh-frozen (FF) or FFPE conditions. To comprehensively evaluate the FFPE RNA-seq data quality for expression profiling, we developed multiple computational methods for assessment, such as the uniformity and continuity …