Survival Analysis 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 …

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 …

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 …

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 …

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 …

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 …

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.

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 …

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 …

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 …

Survival Analysis: A Modified Kaplan-Meir Estimator, Justin A. Bancroft

Graduate Theses/Dissertations

The popular Kaplan-Meir estimator has traditionally been used to great effect as a survival function estimator. However, the Kaplan-Meir estimator is dependent upon a maximum likelihood parameter estimator which may not be the best estimator in all cases. We modify the Kaplan-Meir estimator, based on a Bayes parameter estimation, in hopes of providing a more accurate survival estimator for small sample sizes. Core elements of survival analysis are presented, acting as a foundation from which to construct and compare our modified Kaplan-Meir estimator. It is hypothesized that our modified Kaplan-Meir estimator is generally more accurate than the standard Kaplan-Meir estimator …

Characteristics Of Stem Success: A Survival Analysis Model Of Factors Influencing Time To Graduation Among Undergraduate Stem Majors, Riley K. Acton

Business and Economics Honors Papers

Producing more graduates in Science, Technology, Engineering, and Mathematics (STEM), as well as ensuring students complete college in a timely manner are both areas of national public policy interest. In order to improve these two outcomes, it is imperative to understand what factors lead undergraduate students to persist in, and ultimately graduate with STEM degrees. This paper uses data from the Beginning Postsecondary Students Longitudinal Study, provided by The National Center of Education Statistics, to model the time to baccalaureate degree among STEM majors using a Cox proportional hazard model.

Cox Regression Models With Functional Covariates For Survival Data, Jonathan E. Gellar, Elizabeth Colantuoni, Dale M. Needham, Ciprian M. Crainiceanu

Johns Hopkins University, Dept. of Biostatistics Working Papers

We extend the Cox proportional hazards model to cases when the exposure is a densely sampled functional process, measured at baseline. The fundamental idea is to combine penalized signal regression with methods developed for mixed effects proportional hazards models. The model is fit by maximizing the penalized partial likelihood, with smoothing parameters estimated by a likelihood-based criterion such as AIC or EPIC. The model may be extended to allow for multiple functional predictors, time varying coefficients, and missing or unequally-spaced data. Methods were inspired by and applied to a study of the association between time to death after hospital discharge …

Hypothesis Testing For An Extended Cox Model With Time-Varying Coefficients, Takumi Saegusa, Chongzhi Di, Ying Qing Chen

UW Biostatistics Working Paper Series

The log-rank test has been widely used to test a treatment effect under the Cox model for censored time-to-event outcomes, though it may lose power substantially when the model's proportional hazards assumption does not hold. In this paper, we consider an extended Cox model that uses B-splines or smoothing splines to model a time-varying treatment effect and propose score test statistics for the treatment effect. Our proposed new tests combine statistical evidence from both the magnitude and the shape of the time-varying hazard ratio function, and thus are omnibus and powerful against various types of alternatives. In addition, the new …

Survival Prediction For Brain Tumor Patients Using Gene Expression Data, Vinicius Bonato

Dissertations and Theses (Open Access)

Brain tumor is one of the most aggressive types of cancer in humans, with an estimated median survival time of 12 months and only 4% of the patients surviving more than 5 years after disease diagnosis. Until recently, brain tumor prognosis has been based only on clinical information such as tumor grade and patient age, but there are reports indicating that molecular profiling of gliomas can reveal subgroups of patients with distinct survival rates. We hypothesize that coupling molecular profiling of brain tumors with clinical information might improve predictions of patient survival time and, consequently, better guide future treatment decisions. …

The Joint Distribution Of Bivariate Exponential Under Linearly Related Model, Norou Diawara, Kumer Pial Das

Mathematics & Statistics Faculty Publications

In this paper, fundamental results of the joint distribution of the bivariate exponential distributions are established. The positive support multivariate distribution theory is important in reliability and survival analysis, and we applied it to the case where more than one failure or survival is observed in a given study. Usually, the multivariate distribution is restricted to those with marginal distributions of a specified and familiar lifetime family. The family of exponential distribution contains the absolutely continuous and discrete case models with a nonzero probability on a set of measure zero. Examples are given, and estimators are developed and applied to …

A Note On Targeted Maximum Likelihood And Right Censored Data, Mark J. Van Der Laan, Daniel Rubin

U.C. Berkeley Division of Biostatistics Working Paper Series

A popular way to estimate an unknown parameter is with substitution, or evaluating the parameter at a likelihood based fit of the data generating density. In many cases, such estimators have substantial bias and can fail to converge at the parametric rate. van der Laan and Rubin (2006) introduced targeted maximum likelihood learning, removing these shackles from substitution estimators, which were made in full agreement with the locally efficient estimating equation procedures as presented in Robins and Rotnitzsky (1992) and van der Laan and Robins (2003). This note illustrates how targeted maximum likelihood can be applied in right censored data …

Empirical Efficiency Maximization, Daniel B. Rubin, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

It has long been recognized that covariate adjustment can increase precision, even when it is not strictly necessary. The phenomenon is particularly emphasized in clinical trials, whether using continuous, categorical, or censored time-to-event outcomes. Adjustment is often straightforward when a discrete covariate partitions the sample into a handful of strata, but becomes more involved when modern studies collect copious amounts of baseline information on each subject.

The dilemma helped motivate locally efficient estimation for coarsened data structures, as surveyed in the books of van der Laan and Robins (2003) and Tsiatis (2006). Here one fits a relatively small working model …

Survival Point Estimate Prediction In Matched And Non-Matched Case-Control Subsample Designed Studies, Annette M. Molinaro, Mark J. Van Der Laan, Dan H. Moore, Karla Kerlikowske

U.C. Berkeley Division of Biostatistics Working Paper Series

Providing information about the risk of disease and clinical factors that may increase or decrease a patient's risk of disease is standard medical practice. Although case-control studies can provide evidence of strong associations between diseases and risk factors, clinicians need to be able to communicate to patients the age-specific risks of disease over a defined time interval for a set of risk factors.

An estimate of absolute risk cannot be determined from case-control studies because cases are generally chosen from a population whose size is not known (necessary for calculation of absolute risk) and where duration of follow-up is not …

Survival Ensembles, Torsten Hothorn, Peter Buhlmann, Sandrine Dudoit, Annette M. Molinaro, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

We propose a unified and flexible framework for ensemble learning in the presence of censoring. For right-censored data, we introduce a random forest algorithm and a generic gradient boosting algorithm for the construction of prognostic models. The methodology is utilized for predicting the survival time of patients suffering from acute myeloid leukemia based on clinical and genetic covariates. Furthermore, we compare the diagnostic capabilities of the proposed censored data random forest and boosting methods applied to the recurrence free survival time of node positive breast cancer patients with previously published findings.

Semiparametric Quantitative-Trait-Locus Mapping: Ii. On Censored Age-At-Onset, Ying Qing Chen, Chengcheng Hu, Rongling Wu

U.C. Berkeley Division of Biostatistics Working Paper Series

In genetic studies, the variation in genotypes may not only affect different inheritance patterns in qualitative traits, but may also affect the age-at-onset as quantitative trait. In this article, we use standard cross designs, such as backcross or F2, to propose some hazard regression models, namely, the additive hazards model in quantitative trait loci mapping for age-at-onset, although the developed method can be extended to more complex designs. With additive invariance of the additive hazards models in mixture probabilities, we develop flexible semiparametric methodologies in interval regression mapping without heavy computing burden. A recently developed multiple comparison procedures is adapted …

Loss-Based Estimation With Cross-Validation: Applications To Microarray Data Analysis And Motif Finding, Sandrine Dudoit, Mark J. Van Der Laan, Sunduz Keles, Annette M. Molinaro, Sandra E. Sinisi, Siew Leng Teng

U.C. Berkeley Division of Biostatistics Working Paper Series

Current statistical inference problems in genomic data analysis involve parameter estimation for high-dimensional multivariate distributions, with typically unknown and intricate correlation patterns among variables. Addressing these inference questions satisfactorily requires: (i) an intensive and thorough search of the parameter space to generate good candidate estimators, (ii) an approach for selecting an optimal estimator among these candidates, and (iii) a method for reliably assessing the performance of the resulting estimator. We propose a unified loss-based methodology for estimator construction, selection, and performance assessment with cross-validation. In this approach, the parameter of interest is defined as the risk minimizer for a suitable …

Statistical Inference For Infinite Dimensional Parameters Via Asymptotically Pivotal Estimating Functions, Meredith A. Goldwasser, Lu Tian, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

Tree-Based Multivariate Regression And Density Estimation With Right-Censored Data , Annette M. Molinaro, Sandrine Dudoit, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

We propose a unified strategy for estimator construction, selection, and performance assessment in the presence of censoring. This approach is entirely driven by the choice of a loss function for the full (uncensored) data structure and can be stated in terms of the following three main steps. (1) Define the parameter of interest as the minimizer of the expected loss, or risk, for a full data loss function chosen to represent the desired measure of performance. Map the full data loss function into an observed (censored) data loss function having the same expected value and leading to an efficient estimator …