Biostatistics Commons^™

Extensions Of Discrete Choice Experiment Theory For Public Health, Farahnaz Islam

Theses and Dissertations

A discrete choice experiment (DCE) allows researchers to understand how individuals value characteristics of a product or service in hypothetical scenarios and the trade-offs these individuals are willing to make between these characteristics. DCEs quickly gained traction in public health but as more researchers utilized DCEs in broader contexts, several methodological questions have arisen. This dissertation addresses some of these gaps in the literature.

One critique of DCEs is whether individuals would make the same choice in reality as they claimed they would have made in the hypothetical scenario. Perhaps the most efficient way to evaluate the predictive value of …

Modified Em Algorithm In Smcure Package Based On Proportional Hazards Mixture Cure Model With Offset Terms, Jiaying Yi

Theses and Dissertations

Mixture cure model is a useful method of survival analysis for population including cured proportion and uncured proportion. The R package SMCURE applies EM algorithm to estimate the coefficients of covariates in the mixture cure model. Although an offset term is specified in the SMCURE statement, the offset term is not appropriately handled in the algorithm. This thesis aims to adjust the EM algorithm for the proportional hazards mixture cure model in the SMCURE package. In addition, the offset term can be specified separately in the incidence part or the latency part. The numerical experiments include simulation study and real …

Complex Functional Joint Models For Longitudinal Electronic Health Record, Siyuan Guo

Theses and Dissertations

Longitudinal measurements are important components in electronic health record (EHR) data. In practice, using longitudinal EHR history is expected to improve the estimation or prediction performance when studying some outcomes of interest, such as binary outcome or time to event outcome. However, the longitudinal observations in EHR data is complex due to irregular and sparse EHR visits. Therefore, modelling longitudinal data and further incorporating them with different types of outcomes is challenge. In this dissertation, we aim to develop methodology to first, describe the pattern of the longitudinal predictors with continuous or binary observations, and second, model the longitudinal predictors …

Estimating Weighted Panel Sizes For Primary Care Providers: An Assessment Of Clustering And Novel Methods Of Panel Size Estimation On Electronic Medical Records, Martin A. Lavallee

Theses and Dissertations

Primary Care is on the frontlines of healthcare, thus they see the most diverse set of patients. In order to achieve high functioning primary care, a practice must establish empanelment, the pairing of patients to providers. Enumeration of empanelment, or estimating panel sizes, helps ensure that the demands of the patients demand the supply of providers and optimize the balance of primary care resources to improve quality of care. Further we can adjust panel sizes by using patient-level data on healthcare utilization and complexity extracted from the electronic medial record to determine the amount of care or burden of work …

Multiple Frailty Model For Spatially Correlated Interval-Censored, Wanfang Zhang

Theses and Dissertations

In this paper, we consider the problem of multiple frailty selection for general interval-censored spatial survival data, which often occurs in clinical trials and epidemiological studies. The general interval-censored data is a mixture of left-, right- and interval-censored data. We propose a Bayesian semiparametric approach based on the Cox proportional hazard model, where monotone splines were used for non-parametrical modeling of the cumulative baseline hazards where the variable selection priors were used for frailty selection. A two-stage data augmentation with Poisson latent variables is developed for efficient computation. The approach is evaluated based a simulation study and illustrated using a …

Association Between The Beta Band Neural Response And The Behavioral Performance In Aphasic And Neurologically Intact Individuals, Yilun Zhang

Theses and Dissertations

The complex motor act of speech requires integrating linguistic and sensorimotor processes. Sensorimotor interaction mainly supports speech production in the form of state feedback control architecture. While speaking, subjects react to perturbations in the pitch of voice auditory feedback by changing their tone in the opposite direction to pitch-shift stimuli to compensate for the perceived pitch shift. Aphasia is a communication impairment affecting patients’ speaking, understanding, reading, and writing. The present study aims to examine the association between brain neural activity and the ability for speech auditory feedback error correction in both post-stroke aphasia and neurologically intact individuals. There are …

Marginally Interpretable Models And Multilevel Models For Quantile Regression With Random-Effects, Nahid Sultana Sumi

Theses and Dissertations

The quantile regression model is an active area of statistical research that has received a lot of attention. This complements the most widely used statistical tool, that is, mean regression analysis. Quantile regression analysis It has become more flexible because of its properties that include no assumption on the distribution of the response variable, equivalent to monotone transformations, and robustness to outliers. However, regression analysis offers methodological challenges if the observations are not independent. Cluster, multilevel, and repeated measures (longitudinal data) designs introduce such dependence. The correlation between observations on the same units or clusters should be accounted for to …

Bayesian Calibration Of The Icrp Zirconium Biokinetic Model And Use Of Canned Priors For The Evaluation Of Bioassay, Thomas Raymond Labone

Theses and Dissertations

The International Commission on Radiological Protection (ICRP) publishes biokinetic models that relate measurements of radioactive material in the body and excreta (bioassay) to the amount of the material taken into the body (intake). Given the intake and the biokinetic model, radiation dose to organs and tissues can be calculated. The ICRP approximates the biokinetics of radioactive materials in the body with compartmental models expressed mathematically as a system of ordinary differential equations, for which they provide point estimates of the rate constants. Inaccurate estimates of intake and radiation dose can result in cases where the biokinetics of an individual differ …

Correcting For Measurement Error In The Outcome When Estimating The Distribution Of Time To Pregnancy With The Current Duration Approach, Nicole Nasrallah

Theses and Dissertations

The current duration approach to modeling time-to-pregnancy (TTP) models the length of pregnancy attempt for women that are currently attempting pregnancy. There is a scarcity of studies, let alone TTP studies, that account for measurement error in the outcome. Previously, the benefits of a piecewise constant model with regards to bias in estimates of the survival function with measurement error and the parametric modelling of TTP was shown. In this thesis, correcting for measurement error in the outcome with the current duration approach is explored through piecewise constant models with log-normal measurement error. Five different methods are compared to determine …

A Comparison Of Spatial Clustering Assessment Methods, Nadeesha Dilhani Vidanapathirana

Theses and Dissertations

Spatial clustering detection methods are widely used in many fields of research including sociology, epidemiology, ecology, and criminology. The objective of this study is to assess the performance of four spatial clustering detection methods: the average nearest neighbor ratio, Ripley’s K function, local Moran’s I and Getis-Ord Gi* statistics. We conduct a simulation study to evaluate the performance of each method for areal data under different types of spatial dependence and three different areal structures; a 20x20 regular grid, United States counties in six states and Canadian forward sortation areas (FSAs) in three provinces. The results shows that the empirical …

Accurate And Integrative Detection Of Copy Number Variants With High-Throughput Data, Xizhi Luo

Theses and Dissertations

Copy number variation, as a major source of genetic variation in the human genome, are gains or losses of the DNA segments. Copy number variation has gained considerable interest as it plays important roles in human complex diseases. Therefore, accurate detection of CNVs with data generated by modern genotyping technologies, such as SNP array and whole-exome sequencing (WES), comprises a critical step toward a better understanding of disease etiology. However, current statistical methodologies for CNV detection still face analytical challenges due to numerous genetic and technological factors that may lead to spurious findings. First, existing methods assume the independent observations …

A Simulation-Based Study Of Location-Shift Models Under Non-Normal Conditions, Ummay Khayrunnesa Anika

Theses and Dissertations

In this study, we compare ordinary least squares (OLS), generalized least squares (GLS), M- and quantile regression (QR) estimators for a continuous response variable under different scenarios by conducting a simulation study. We assess the performance of the estimators in terms of bias, average distance, mean squared error, coverage probability, and ratio of estimated standard error and empirical standard deviation. OLS estimator performs the best when the errors are homoscedastic normal or homoscedastic but skewed (exponential) having no outliers. GLS estimator shows good comparative results to QR when the errors are heteroscedastic normal or heteroscedastic heavy-tailed (t-distributed). The most satisfactory …

Statistical Approaches For Estimation And Comparison Of Brain Functional Connectivity, Jifang Zhao

Theses and Dissertations

Drug addiction can lead to many health-related problems and social concerns. Functional connectivity obtained from functional magnetic resonance imaging (fMRI) data promotes a variety of fundamental understandings in such association. Due to its complex correlation structure and large dimensionality, the modeling and analysis of the functional connectivity from neuroimage are challenging. By proposing a spatio-temporal model for multi-subject neuroimage data, we incorporate voxel-level spatio-temporal dependencies of whole-brain measurements to improve the accuracy of statistical inference. To tackle large-scale spatio-temporal neuroimage data, we develop a computationally efficient algorithm to estimate the parameters. Our method is used to identify functional connectivity and …

Methods For Developing A Machine Learning Framework For Precise 3d Domain Boundary Prediction At Base-Level Resolution, Spiro C. Stilianoudakis

Theses and Dissertations

High-throughput chromosome conformation capture technology (Hi-C) has revealed extensive DNA looping and folding into discrete 3D domains. These include Topologically Associating Domains (TADs) and chromatin loops, the 3D domains critical for cellular processes like gene regulation and cell differentiation. The relatively low resolution of Hi-C data (regions of several kilobases in size) prevents precise mapping of domain boundaries by conventional TAD/loop-callers. However, high resolution genomic annotations associated with boundaries, such as CTCF and members of cohesin complex, suggest a computational approach for precise location of domain boundaries.

We developed preciseTAD, an optimized machine learning framework that leverages a random …

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 …

Prognostic Modeling Of Recovery Following Stem Cell Transplantation, Brielle A. Forsthoffer

Theses and Dissertations

Predicting the trajectory of lymphoid recovery following myeloablative hematopoietic stem cell transplantation (SCT) can help guide subsequent therapeutic decisions, since poor recovery has been associated with graft-versus-host disease (GVHD), relapse and mortality. Previous attempts at classifying patients depended on absolute criteria being set prior to modeling absolute lymphocyte counts (ALCs) over time. Having an empirical clinical decision support tool for objectively determining the trajectory an individual might take during their recovery would be advantageous. We propose using growth-based trajectory modeling (GBTM) and growth mixture modeling (GMM), which utilize machine learning algorithms to empirically identify latent groupings of data. Due to …

Bayesian Techniques For Relating Genetic Polymorphisms To Diffusion Tensor Images Of Cocaine Users, Tmader Alballa

Theses and Dissertations

Past investigations utilizing Diffusion Tensor Imaging (DTI) have demonstrated that cocaine use disorder (CUD) yields white matter changes. We proposed three Bayesian techniques in order to explore the relationship between Fractional Anisotropy (FA), genetic data, and years of cocaine use (YCU). CUD participants exhibit abnormality in different areas of the brain versus non-drug using controls, which is measured by DTI. This dissertation is motivated by a neuroimaging genetic study in cocaine dependence, which found that there were relationships between several genes such as GAD and 5-HT₂R and CUD subjects.

In the first chapter, there is background on the …

Incorporation And Measurement Of Uncertainty In Clustered And Spatial Data, Yuan Hong

Theses and Dissertations

Analyzing population representative datasets for local estimation and predictions over time is important for monitoring related public health issues, however, there are many statistical challenges associated with such analyses. Mixed effect models are one of the common options which can incorporate time and spatial effect in the model and related inference is well established.

In the first part of this dissertation, to estimate area-level prevalence using individuallevel data, small area estimation (SAE) with post-stratified mixed effect models were used where sampling weights were also incorporated into it. However, if poststratification which requires more computation effort can improve estimation accuracy is …

A Study Of The Efficacy Of Machine Learning For Diagnosing Obstructive Coronary Artery Disease In Non-Diabetic Patients, Demond Larae Handley

Theses and Dissertations

According to the Centers for Disease Control and Prevention, about 18.2 million adults age 20 and older have Coronary Artery Disease in the United States. Early diagnosis is therefore of crucial importance to help prevent debilitating consequences, and principally death for many patients. In this study we use data containing gene expression values from peripheral blood samples in 198 non-diabetic patients, with the goal of developing an age and sex gene expression model for diagnosis of Coronary Artery Disease. We employ machine learning methods to obtain a classification based on genetic information, age and sex. Our implementation uses feed forward …

The Practical Advantages And Disadvantages Of Laplace Regression As An Alternative To Cox Proportional Hazards Model: A Comparison Via Simulation, Sydney Smith

Theses and Dissertations

The Cox proportional hazards model is the most common regression technique for survival analysis. However, the proportional hazards assumption restricts it’s use to a limited group of multiplicative models. Laplace regression is a flexible quantile regression technique for censored observations that is appropriate in a wider variety of applications as compared to the Cox proportional hazards model. Instead of estimating a hazard ratio, Laplace regression which is free from a proportionality assumption, can be used to estimate many adjusted percentiles of survival time allowing for a more complete description of the association of interest. This paper compares the performance of …

Network-Based Statistical Analysis Of Functional Magnetic Resonance Imaging Data From Aphasia Patients, Xingpei Zhao

Theses and Dissertations

Functional magnetic resonance imaging (fMRI) is a neuroimaging technique that provides insight into brain function and activity. Network models of fMRI signals can reveal functional connectivity related to certain brain disorders, such as post-stroke aphasia. This thesis aims to identify the functional connections that distinguish anomic and Broca’s aphasia by comparing the resting-state fMRI from the patients with these two types of aphasia. The network-based statistic (NBS) approach is used to detect such connections. After the analytic pipeline is applied to the fMRI data, the NBS approach identifies a distinct subnetwork between the two types of aphasia, which involves the …

Bayesian Zero-Inflated Model For Ordinal Data, Huizhong Yang

Theses and Dissertations

Datasets with a relatively large number of zeros is commonly seen in medical applications. Although models like Zero-inflated Poisson (ZIP) model are proposed for counts data, there is still some issues with ordinal data which have excess zeros. In this paper, we developed a Bayesian approach to accommodate the excess zero in ordinal data. Intellectual disability (ID), also known as mental retardation (MR), is a disability characterized by below-average intelligence or mental ability and a lack of the learning necessary skills for daily life. A person with intellectual disability has intellectual functioning and adaptive behaviors limitations. Intellectual disability is a …

Multivariate Joint Models And Dynamic Predictions, Md Akhtar Hossain

Theses and Dissertations

The joint modeling of longitudinal and time-to-event data is an active area of statistical research that has received a lot of attention. The standard joint models, referred to as univariate joint models, allow simultaneous modeling of a single longitudinal outcome and a single time-to-event under an assumption of independent censoring. The majority of the joint modeling research in the last two decades has focused on extending and improving the univariate joint models. While many of the practical applications involve data on multivariate longitudinal outcomes and multiple timeto- events possibly informatively censored by some other terminal time-to-event, the developments of joint …

Integrated Multiple Adaptive Design Involving Sample Size Re-Estimation And (Covariate-Adjusted) Response-Adaptive Randomization For Continuous And Binary Outcomes, Christine M. Orndahl

Theses and Dissertations

Historically, clinical trials have been performed based on decisions made prior to the start of the trial. Adaptive designs have been developed to provide increased flexibility, allowing pre-specified changes to occur based on interim data. Each adaptive design addresses a unique pitfall of a non-adaptive design, such as minimizing the chance of an under- or over-powered study by utilizing interim data to update the sample size estimate (sample size re-estimation) or increasing the ethical benefit of a trial by allocating more participants to the better performing treatment group ([covariate-adjusted] response-adaptive randomization). Additional benefit is attainable by combining more than one …

Adjusting For Dropout In Randomized Controlled Clinical Trials, Katharine Stromberg

Theses and Dissertations

Dropout is a common issue in randomized controlled clinical trials and can negatively impact the internal validity of a study and potentially bias the treatment effect. When subjects discontinue study participation, they are not being given the opportunity to gain from the investigational therapy as if they had remained in the study, defeating one of the main purposes of clinical trials, providing treatment. Specifically in unblinded studies, such as the wait-list control (WLC) design, dropout is often due to group membership. Subjects allocated to the control group often dropout at higher rates than in the treatment group. Adaptive designs have …

Zero-Inflated Longitudinal Mixture Model For Stochastic Radiographic Lung Compositional Change Following Radiotherapy Of Lung Cancer, Viviana A. Rodríguez Romero

Theses and Dissertations

Compositional data (CD) is mostly analyzed as relative data, using ratios of components, and log-ratio transformations to be able to use known multivariable statistical methods. Therefore, CD where some components equal zero represent a problem. Furthermore, when the data is measured longitudinally, observations are spatially related and appear to come from a mixture population, the analysis becomes highly complex. For this matter, a two-part model was proposed to deal with structural zeros in longitudinal CD using a mixed-effects model. Furthermore, the model has been extended to the case where the non-zero components of the vector might a two component mixture …

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 …

Estimating Response Status In Sequential Multiple Assignment (Smar)-Like Trials, Keighly Bradbrook

Theses and Dissertations

Sequential, multiple assignment, randomized trials (SMARTs) allow investigators to develop and compare experimental treatment regimens in which individuals are successively randomized to different treatments based on some set of predetermined rules. The rules used to make decisions on when and how to switch treatments are based on a chosen set of tailoring variables. Although not always true, intermediate response is commonly used as the primary tailoring variable as it is often predictive of future treatment success. As such, successful implementation depends on identifying patients who respond to treatment, though in some situations such mechanisms may not exist. Further, patient-level covariates …

The Analysis Of Neural Heterogeneity Through Mathematical And Statistical Methods, Kyle Wendling

Theses and Dissertations

Diversity of intrinsic neural attributes and network connections is known to exist in many areas of the brain and is thought to significantly affect neural coding. Recent theoretical and experimental work has argued that in uncoupled networks, coding is most accurate at intermediate levels of heterogeneity. I explore this phenomenon through two distinct approaches: a theoretical mathematical modeling approach and a data-driven statistical modeling approach.

Through the mathematical approach, I examine firing rate heterogeneity in a feedforward network of stochastic neural oscillators utilizing a high-dimensional model. The firing rate heterogeneity stems from two sources: intrinsic (different individual cells) and network …

Extension Of Risk-Based Measure Of Time-Varying Prognostic Discrimination For Survival Models, Shujie Chen

Theses and Dissertations

The Cox proportional hazards (PH) model and time dependent PH model are the most popular survival models in survival analysis. The hazard discrimination summary HDS(t) proposed by Liang and Heagerty [2017] is used to evaluate the mean hazard difference between cases and controls at time t. Liang and Heagerty [2017] evaluated the discrimination performance under the PH model and time dependent PH model with right censoring.

In this thesis, first, we further investigate their method via comprehensive simulations including 1) We extend the simulation in Liang and Heagerty [2017] under the PH model by adding more scenarios such as different …