Statistical Models 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 …

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. …

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 …

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 …

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 …

Comparison Of Hazard, Odds And Risk Ratio In The Two-Sample Survival Problem, Benedict P. Dormitorio

Dissertations

Cox proportional hazards is the standard method for analyzing treatment efficacy when time-to-event data is available. In the absence of time-to-event, investigators may use logistic regression which only requires relative frequencies of events, or Poisson regression which requires only interval-summarized frequency tables of time-to-event. When event frequencies are used instead of time-to-events, does it always result in a loss in power?

We investigate the relative performance of the three methods. In particular, we compare the power of tests based on the respective effect-size estimates (1)hazard ratio (HR), (2)odds ratio (OR), and (3)risk ratio (RR). We use a variety of survival …

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 …

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 …

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 …