Statistics and Probability Commons^™

Analysis Of Genetic Variants Associated With Levels Of Immune Modulating Proteins For Impact On Alzheimer’S Disease Risk Reveal A Potential Role For Siglec14, Benjamin C. Shaw, Yuriko Katsumata, James F. Simpson, David W. Fardo, Steven Estus

Biostatistics Faculty Publications

Genome-wide association studies (GWAS) have identified immune-related genes as risk factors for Alzheimer’s disease (AD), including TREM2 and CD33, frequently passing a stringent false-discovery rate. These genes either encode or signal through immunomodulatory tyrosine-phosphorylated inhibitory motifs (ITIMs) or activation motifs (ITAMs) and govern processes critical to AD pathology, such as inflammation and amyloid phagocytosis. To investigate whether additional ITIM and ITAM-containing family members may contribute to AD risk and be overlooked due to the stringent multiple testing in GWAS, we combined protein quantitative trait loci (pQTL) data from a recent plasma proteomics study with AD associations in a recent …

A Highly Predictive Microrna Panel For Determining Delayed Cerebral Vasospasm Risk Following Aneurysmal Subarachnoid Hemorrhage, Wang-Xia Wang, Joe E. Springer, Kevin Xie, David W. Fardo, Kevin W. Hatton

Sanders-Brown Center on Aging Faculty Publications

Approximately one-third of aneurysmal subarachnoid hemorrhage (aSAH) patients develop delayed cerebral vasospasm (DCV) 3–10 days after aneurysm rupture resulting in additional, permanent neurologic disability. Currently, no validated biomarker is available to determine the risk of DCV in aSAH patients. MicroRNAs (miRNAs) have been implicated in virtually all human diseases, including aSAH, and are found in extracellular biofluids including plasma and cerebrospinal fluid (CSF). We used a custom designed TaqMan Low Density Array miRNA panel to examine the levels of 47 selected brain and vasculature injury related miRNAs in CSF and plasma specimens collected from 31 patients with or without DCV …

Cardiovascular Complications Of Systemic Lupus Erythematosus: Impact Of Risk Factors And Therapeutic Efficacy--A Tertiary Centre Experience In An Appalachian State, Elise Danielle Mcveigh, Amna Batool, Arnold J. Stromberg, Ahmed K. Abdel-Latif, Nayef Mohammed Kazzaz

Statistics Faculty Publications

OBJECTIVES: Cardiovascular complications became a notable cause of morbidity and mortality in patients with lupus as therapeutic advancements became more efficient at managing other complications. The Appalachian community in Kentucky has a higher prevalence of traditional cardiovascular risk factors, predisposing them to cardiovascular events. Namely, the mean body mass index of the members of the Kentucky Appalachian community was reported at 33 kg/m² and 94.3% of male members of this community use tobacco. We sought to identify risk factors that predispose patients with lupus to cardiovascular morbidities and examine the effect of immunomodulatory drugs.

METHODS: We identified 20 UKHS …

Epigenome-Wide Association Study Of Kidney Function Identifies Trans-Ethnic And Ethnic-Specific Loci, Charles E. Breeze, Anna Batorsky, Mi Kyeong Lee, Mindy D. Szeto, Xiaoguang Xu, Daniel L. Mccartney, Rong Jiang, Amit Patki, Holly J. Kramer, James M. Eales, Laura Raffield, Leslie Lange, Ethan Lange, Peter Durda, Yongmei Liu, Russ P. Tracy, David Van Den Berg, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Topmed Mesa Multi-Omics Working Group, Kathryn L. Evans, William E. Kraus, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach.

METHODS: The study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear …

Disability-Free Life Expectancy Among People Over 60 Years Old By Sex, Urban And Rural Areas In Jiangxi Province, China, Shengwei Wang, Songbo Hu, Pei Wang, Yuhang Wu, Zhitao Liu, Huilie Zheng

Statistics Graduate Research

Objective: To estimate and compare age trends and the disability-free life expectancy (DFLE) of the population over 60 years old in 2018 in Jiangxi Province, China, by sex and urban–rural areas. Methods: The model life table was employed to estimate the age-specific mortality rate by sex and urban–rural areas, based on the Summary of Health Statistics of Jiangxi Province in 2018 and the Sixth National Health Service survey of Jiangxi Province. DFLE and its ratio to life expectancy (LE) were obtained by the Sullivan method. Results: In 2018, the DFLE among people over 60 is 17.157 years for men and …

An Ensemble Of The Icluster Method To Analyze Longitudinal Lncrna Expression Data For Psoriasis Patients, Suyan Tian, Chi Wang

Internal Medicine Faculty Publications

BACKGROUND: Psoriasis is an immune-mediated, inflammatory disorder of the skin with chronic inflammation and hyper-proliferation of the epidermis. Since psoriasis has genetic components and the diseased tissue of psoriasis is very easily accessible, it is natural to use high-throughput technologies to characterize psoriasis and thus seek targeted therapies. Transcriptional profiles change correspondingly after an intervention. Unlike cross-sectional gene expression data, longitudinal gene expression data can capture the dynamic changes and thus facilitate causal inference.

METHODS: Using the iCluster method as a building block, an ensemble method was proposed and applied to a longitudinal gene expression dataset for psoriasis, with the …

Chromosome Xq23 Is Associated With Lower Atherogenic Lipid Concentrations And Favorable Cardiometabolic Indices, Pradeep Natarajan, Akhil Pampana, Sarah E. Graham, Sanni E. Ruotsalainen, James A. Perry, Paul S. De Vries, Jai G. Broome, James P. Pirruccello, Michael C. Honigberg, Krishna Aragam, Brooke Wolford, Jennifer A. Brody, Lucinda Antonacci-Fulton, Moscati Arden, Stella Aslibekyan, Themistocles L. Assimes, Christie M. Ballantyne, Lawrence F. Bielak, Joshua C. Bis, Brian E. Cade, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10⁻⁷²), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 …

Age And Sex Are Associated With The Plasma Lipidome: Findings From The Goldn Study, Emily Slade, Marguerite R. Irvin, Kevin Xie, Donna K. Arnett, Steven A. Claas, Tobias Kind, David W. Fardo, Gregory A. Graf

Biostatistics Faculty Publications

Background
Developing an understanding of the biochemistry of aging in both sexes is critical for managing disease throughout the lifespan. Lipidomic associations with age and sex have been reported, but prior studies are limited by measurements in serum rather than plasma or by participants taking lipid-lowering medications.

Methods
Our study included lipidomic data from 980 participants aged 18–87 years old from the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN). Participants were off lipid-lowering medications for at least 4 weeks, and signal intensities of 413 known lipid species were measured in plasma. We examined linear age and sex associations with …

Generalized Fiducial Inference On The Mean Of Zero-Inflated Poisson And Poisson Hurdle Models, Yixuan Zou, Jan Hannig, Derek S. Young

Statistics Faculty Publications

Zero-inflated and hurdle models are widely applied to count data possessing excess zeros, where they can simultaneously model the process from how the zeros were generated and potentially help mitigate the effects of overdispersion relative to the assumed count distribution. Which model to use depends on how the zeros are generated: zero-inflated models add an additional probability mass on zero, while hurdle models are two-part models comprised of a degenerate distribution for the zeros and a zero-truncated distribution. Developing confidence intervals for such models is challenging since no closed-form function is available to calculate the mean. In this study, generalized …

Validation Of Icd-10-Cm Codes For Injuries Complicating Pregnancy, Childbirth And The Puerperium: A Medical Record Review, Anna Hansen, Dana Quesinberry, Peter Akpunonu, Julia Martin, Svetla Slavova

Kentucky Injury Prevention and Research Center Faculty Publications

INTRODUCTION: The purpose of this study was to estimate the positive predictive value (PPV) of International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes for injury, poisoning, physical or sexual assault complicating pregnancy, childbirth and the puerperium (PCP) to capture injury encounters within both hospital and emergency department claims data.

METHODS: A medical record review was conducted on a sample (n=157) of inpatient and emergency department claims from one Kentucky healthcare system from 2015 to 2017, with any diagnosis in the ICD-10-CM range O9A.2-O9A.4. Study clinicians reviewed medical records for the sampled cases and used an abstraction form to …

Rural Residents' Perspectives On An Mhealth Or Personalized Health Coaching Intervention: Qualitative Study With Focus Groups And Key Informant Interviews, Nancy Schoenberg, Madeline Dunfee, Hannah Yeager, Matthew Rutledge, Angela Pfammatter, Bonnie Spring

Behavioral Science Faculty Publications

BACKGROUND: Compared with national averages, rural Appalachians experience extremely elevated rates of premature morbidity and mortality. New opportunities, including approaches incorporating personal technology, may help improve lifestyles and overcome health inequities.

OBJECTIVE: This study aims to gather perspectives on whether a healthy lifestyle intervention, specifically an app originally designed for urban users, may be feasible and acceptable to rural residents. In addition to a smartphone app, this program-Make Better Choices 2-consists of personalized health coaching, accelerometer use, and financial incentives.

METHODS: We convened 4 focus groups and 16 key informant interviews with diverse community stakeholders to assess perspectives on this …

Real World Clinicopathologic Observations Of Patients With Metastatic Solid Tumors Receiving Immune Checkpoint Inhibitor Therapy: Analysis From Kentucky Cancer Registry, Aasems Jacob, Jianrong Wu, Jill M. Kolesar, Eric B. Durbin, Aju Mathew, Susanne Arnold, Aman Chauhan

Biostatistics Faculty Publications

The state of Kentucky has the highest cancer incidence and mortality in the United States. High‐risk populations such as this are often underrepresented in clinical trials. The study aims to do a comprehensive analysis of molecular landscape of metastatic cancers among these patients with detailed evaluation of factors affecting response and outcomes to immune checkpoint inhibitor (ICI) therapy. We performed a retrospective analysis of metastatic solid tumor patients who received ICI and underwent molecular profiling at our institution.

Sixty nine patients with metastatic solid tumors who received ICI were included in the study. Prevalence of smoking and secondhand tobacco exposure …

Whole-Exome Sequencing And Hipsc Cardiomyocyte Models Identify Myrip, Trappc11, And Slc27a6 Of Potential Importance To Left Ventricular Hypertrophy In An African Ancestry Population, Marguerite R. Irvin, Praful Aggarwal, Steven A. Claas, Lisa De Las Fuentes, Anh N. Do, C. Charles Gu, Andrea Matter, Benjamin S. Olson, Amit Patki, Karen Schwander, Joshua D. Smith, Vinodh Srinivasasainagendra, Hemant K. Tiwari, Amy J. Turner, Deborah A. Nickerson, Dabeeru C. Rao, Ulrich Broeckel, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background: Indices of left ventricular (LV) structure and geometry represent useful intermediate phenotypes related to LV hypertrophy (LVH), a predictor of cardiovascular (CV) disease (CVD) outcomes.

Methods and Results: We conducted an exome-wide association study of LV mass (LVM) adjusted to height^2.7, LV internal diastolic dimension (LVIDD), and relative wall thickness (RWT) among 1,364 participants of African ancestry (AAs) in the Hypertension Genetic Epidemiology Network (HyperGEN). Both single-variant and gene-based sequence kernel association tests were performed to examine whether common and rare coding variants contribute to variation in echocardiographic traits in AAs. We then used a data-driven …

Measurement Matters: Changing Penalty Calculations Under The Hospital Acquired Condition Reduction Program (Hacrp) Cost Hospitals Millions, Olga A. Vsevolozhskaya, Karina C. Manz, Pierre M. Zephyr, Teresa M. Waters

Biostatistics Faculty Publications

BACKGROUND: Since October 2014, the Centers for Medicare and Medicaid Services has penalized 25% of U.S. hospitals with the highest rates of hospital-acquired conditions under the Hospital Acquired Conditions Reduction Program (HACRP). While early evaluations of the HACRP program reported cumulative reductions in hospital-acquired conditions, more recent studies have not found a clear association between receipt of the HACRP penalty and hospital quality of care. We posit that some of this disconnect may be driven by frequent scoring updates. The sensitivity of the HACRP penalties to updates in the program's scoring methodology has not been independently evaluated.

METHODS: We used …

Mental Health And Psychosocial Functioning In Recently Separated U.S. Women Veterans: Trajectories And Bi-Directional Relationships, Karen A. Lawrence, Dawne Vogt, Adam Dugan, Shawn R. Nigam, Emily Slade, Brian N. Smith

Social Work Faculty Publications

Prior research on the relationship between veterans’ mental health and psychosocial functioning has primarily relied on male samples. Here, we investigated prospective longitudinal relationships between mental health and psychosocial functioning in 554 female Iraq and Afghanistan War veterans who were surveyed three times between two- and seven-years following separation from service. Mixed effects modeling revealed that increasing depression and posttraumatic stress disorder (PTSD) severity predicted declines in work functioning. Increasing PTSD severity predicted declining parental functioning and worsening depression predicted a decline in relationship functioning. In turn, decreased work and intimate relationship functioning predicted increased PTSD and depression symptom severity …

Impact Of Patient Load On The Quality Of Electronic Medical Record Documentation, Aasems Jacob, Rishi Raj, Sayee Alagusundaramoorthy, Jing Wei, Jianrong Wu, Margaret Eng

Internal Medicine Faculty Publications

Objective:

American College of Graduate Medical Education (ACGME) recommends ongoing care of 10 patients per resident however its implication is unclear. We hypothesized EMR quality to vary based on patient load and call status.

Methods:

We conducted a double-blind, single-center, retrospective observational study between 2017 and 2019 to investigate the quality and accuracy of resident documentation using the Responsible Electronic Documentation (RED) Checklist, a validated scoring system.

Results:

A total of 234 independent charts were analyzed and 80 met scoring criteria. Average patients per residents was 4, 9.1, 7.2, and 5.5 on “call” day (D0), “post-call” day (D1), “mid-call” day …

Memory-Related Frontal Brainwaves Predict Transition To Mild Cognitive Impairment In Healthy Older Individuals Five Years Before Diagnosis, Yang Jiang, Juan Li, Frederick A. Schmitt, Gregory A. Jicha, Nancy B. Munro, Xiaopeng Zhao, Charles D. Smith, Richard J. Kryscio, Erin L. Abner

Behavioral Science Faculty Publications

BACKGROUND: Early prognosis of high-risk older adults for amnestic mild cognitive impairment (aMCI), using noninvasive and sensitive neuromarkers, is key for early prevention of Alzheimer's disease. We have developed individualized measures in electrophysiological brain signals during working memory that distinguish patients with aMCI from age-matched cognitively intact older individuals.

OBJECTIVE: Here we test longitudinally the prognosis of the baseline neuromarkers for aMCI risk. We hypothesized that the older individuals diagnosed with incident aMCI already have aMCI-like brain signatures years before diagnosis.

METHODS: Electroencephalogram (EEG) and memory performance were recorded during a working memory task at baseline. The individualized baseline neuromarkers, …

Improving Evidence-Based Grouping Of Transitional Care Strategies In Hospital Implementation Using Statistical Tools And Expert Review, Jing Li, Gaixin Du, Jessica Miller Clouser, Arnold J. Stromberg, Glen Mays, Joann Sorra, Jane Brock, Terry Davis, Suzanne Mitchell, Huong Q. Nguyen, Mark V. Williams

Center for Health Services Research Faculty Publications

BACKGROUND: As health systems transition to value-based care, improving transitional care (TC) remains a priority. Hospitals implementing evidence-based TC models often adapt them to local contexts. However, limited research has evaluated which groups of TC strategies, or transitional care activities, commonly implemented by hospitals correspond with improved patient outcomes. In order to identify TC strategy groups for evaluation, we applied a data-driven approach informed by literature review and expert opinion.

METHODS: Based on a review of evidence-based TC models and the literature, focus groups with patients and family caregivers identifying what matters most to them during care transitions, and expert …

Mitochondria Exert Age-Divergent Effects On Recovery From Spinal Cord Injury, Andrew N. Stewart, Katelyn E. Mcfarlane, Hemendra J. Vekaria, William M. Bailey, Stacey A. Slone, Lauren A. Tranthem, Bei Zhang, Samir P. Patel, Patrick G. Sullivan, John C. Gensel

Physiology Faculty Publications

The extent that age-dependent mitochondrial dysfunction drives neurodegeneration is not well understood. This study tested the hypothesis that mitochondria contribute to spinal cord injury (SCI)-induced neurodegeneration in an age-dependent manner by using 2,4-dinitrophenol (DNP) to uncouple electron transport, thereby increasing cellular respiration and reducing reactive oxygen species (ROS) production. We directly compared the effects of graded DNP doses in 4- and 14-month-old (MO) SCI-mice and found DNP to have increased efficacy in mitochondria isolated from 14-MO animals. In vivo, all DNP doses significantly exacerbated 4-MO SCI neurodegeneration coincident with worsened recovery. In contrast, low DNP doses (1.0-mg/kg/day) improved tissue …

Maternal Proximity To Mountaintop Removal Mining And Birth Defects In Appalachian Kentucky, 1997-2003, Daniel B. Cooper

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Background: Extraction of coal through mountaintop removal mining (MTR) alters many dimensions of the landscape, and explosive blasts, exposed rock, and coal washing have the potential to pollute air and water with substances known to increase risk of developmental and birth anomalies. Previous research suggests that infants born to mothers living in MTR coal mining counties have higher prevalence of most types of birth defects.

Objectives: This study seeks to examine further the relationship between MTR activity and birth defects by employing individual level exposure estimation through precise satellite data of MTR activity in the Appalachian region and maternal residence …

Biofilm And Cell Adhesion Strength On Dental Implant Surfaces Via The Laser Spallation Technique, James D. Boyd, Arnold J. Stromberg, Craig S. Miller, Martha E. Grady

Statistics Faculty Publications

OBJECTIVE: The aims of this study are to quantify the adhesion strength differential between an oral bacterial biofilm and an osteoblast-like cell monolayer to a dental implant-simulant surface and develop a metric that quantifies the biocompatible effect of implant surfaces on bacterial and cell adhesion.

METHODS: High-amplitude short-duration stress waves generated by laser pulse absorption are used to spall bacteria and cells from titanium substrates. By carefully controlling laser fluence and calibration of laser fluence with applied stress, the adhesion difference between Streptococcus mutans biofilms and MG 63 osteoblast-like cell monolayers on smooth and rough titanium substrates is obtained. The …

Investigations Into The Genetics Of Mixed Pathologies In Dementia, Adam Dugan

Theses and Dissertations--Epidemiology and Biostatistics

Alzheimer’s disease (AD) is an irreversible, progressive brain disorder that leads to a loss of memory and thinking skills. While tremendous progress has been made in our understanding of the genetics underlying AD, currently known genetic variants explain only approximately 30% of the heritable risk of developing AD. One hurdle to AD research is that it can only be definitively diagnosed at autopsy, making cruder, clinic-based diagnoses more common. In recent years, several brain pathologies that mimic AD’s clinical presentation have been identified including brain arteriolosclerosis, hippocampal sclerosis (HS), and, most recently, limbic-predominant age-related TDP-43 encephalopathy (LATE). It has become …

Design And Analyses Of School-Based Violence Prevention Cluster Randomized Trials, Md. Tofial Azam

Theses and Dissertations--Epidemiology and Biostatistics

Interpersonal violence such as teen dating violence is a severe public health problem. Teen dating violence, including sexual violence (unwanted sexual contacts or activities), physical and psychological dating violence, sexual harassment, and stalking, affects high school students' physical and mental health and academic achievement in the United States. Dating violence is linked to psychological abuse perpetration in the future, depression, anxiety, and hostility. The teen dating violence victimization experience was related to antisocial behavior, drug abuse, increased heavy drinking, depression, suicidal ideation, smoking, and adult interpersonal violence victimization during adolescence. The detrimental effects of interpersonal violence demonstrate the critical importance …

Evaluating The Incidence Of Melanoma And Lung Cancer Of Current And Former Active-Duty U.S. Military Who Were Deployed In Support Of Operation Enduring Freedom And Operation Iraqi Freedom, Brian Kovacic

Theses and Dissertations--Epidemiology and Biostatistics

The incidence of melanoma and lung cancer has been gradually increasing in the United States over the past three decades with the reputed causes due to etiological and environmental exposures, and tobacco usage. There has been concern that melanoma and lung cancer incidence among military personnel may be associated with deployment to environments with intense sun exposure and increased smoking rates due to post-traumatic stress disorder. The aim of this study was to examine associations between deployment in support of Operation Enduring Freedom (OEF) or Operation Iraqi Freedom (OIF), from 2001 through 2015, with subsequent melanoma and lung cancer incidence. …

Sexual Behaviors Associated With Online Partner-Seeking Among Men Who Have Sex With Men From Small/Midsized Towns Or Rural Areas In Kentucky, Vira Pravosud

Theses and Dissertations--Epidemiology and Biostatistics

The HIV epidemic remains one of the most significant public health issues in the United States, particularly among men who have sex with men (MSM). New avenues for partner-seeking have emerged over the past three decades, including through the Internet, social media, and geosocial networking applications. Consisting of three cross-sectional studies, this dissertation research aimed to determine associations between the use of various online tools for partner-seeking (hereafter collectively referred to as “apps”) and HIV-related sexual behaviors among 252 young adult MSM residing in small/midsized towns or rural areas in Central Kentucky, a group that has been under-represented in the …

Dimension Reduction Techniques In Regression, Pei Wang

Theses and Dissertations--Statistics

Because of the advances of modern technology, the size of the collected data nowadays is larger and the structure is more complex. To deal with such kinds of data, sufficient dimension reduction (SDR) and reduced rank (RR) regression are two powerful tools. This dissertation focuses on these two tools and it is composed of three projects. In the first project, we introduce a new SDR method through a novel approach of feature filter to recover the central mean subspace exhaustively along with a method to determine the dimension, two variable selection methods, and extensions to multivariate response and large p …

Novel Nonparametric Testing Approaches For Multivariate Growth Curve Data: Finite-Sample, Resampling And Rank-Based Methods, Ting Zeng

Theses and Dissertations--Statistics

Multivariate growth curve data naturally arise in various fields, for example, biomedical science, public health, agriculture, social science and so on. For data of this type, the classical approach is to conduct multivariate analysis of variance (MANOVA) based on Wilks' Lambda and other multivariate statistics, which require the assumptions of multivariate normality and homogeneity of within-cell covariance matrices. However, data being analyzed nowadays show marked departure from multivariate normal distribution and homoscedasticity. In this dissertation, we investigate nonparametric testing approaches for multivariate growth curve data from three aspects, i.e., finite-sample, resampling and rank-based methods.

The first project proposes an approximate …

Novel Methods For Characterizing Conditional Quantiles In Zero-Inflated Count Regression Models, Xuan Shi

Theses and Dissertations--Statistics

Despite its popularity in diverse disciplines, quantile regression methods are primarily designed for the continuous response setting and cannot be directly applied to the discrete (or count) response setting. There can also be challenges when modeling count responses, such as the presence of excess zero counts, formally known as zero-inflation. To address the aforementioned challenges, we propose a comprehensive model-aware strategy that synthesizes quantile regression methods with estimation of zero-inflated count regression models. Various competing computational routines are examined, while residual analysis and model selection procedures are included to validate our method. The performance of these methods is characterized through …

Estimating And Testing Treatment Effects With Misclassified Multivariate Data, Zi Ye

Theses and Dissertations--Statistics

Clinical trials are often used to assess drug efficacy and safety. Participants are sometimes pre-stratified into different groups by diagnostic tools. However, these diagnostic tools are fallible. The traditional method ignores this problem and assumes the diagnostic devices are perfect. This assumption will lead to inefficient and biased estimators. In this era of personalized medicine and measurement-based care, the issues of bias and efficiency are of paramount importance. Despite the prominence, only few researches evaluated the treatment effect in the presence of misclassifications in some special cases and most others focus on assessing the accuracy of the diagnostic devices. In …

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. …