Biostatistics Commons^™

Statistical Methods For Environmental Exposure Data Subject To Detection Limits, Yuchen Yang

Theses and Dissertations--Statistics

In this dissertation, we develop unified and efficient nonparametric statistical methods for estimating and comparing environmental exposure distributions in presence of detection limits. In the first part, we propose a kernel-smoothed nonparametric estimator for the exposure distribution without imposing any independence assumption between the exposure level and detection limit. We show that the proposed estimator is consistent and asymptotically normal. Simulation studies demonstrate that the proposed estimator performs well in practical situations. A colon cancer study is provided for illustration. In the second part, we develop a class of test statistics to compare exposure distributions between two groups by using …

A Pairwise Likelihood Augmented Estimator For The Cox Model Under Left-Truncation, Fan Wu, Sehee Kim, Jing Qin, Rajiv Saran, Yi Li

The University of Michigan Department of Biostatistics Working Paper Series

Survival data collected from prevalent cohorts are subject to left-truncation and the analysis is challenging. Conditional approaches for left-truncated data under the Cox model are inefficient as they typically ignore the information in the marginal likelihood of the truncation times. Length-biased sampling methods can improve the estimation efficiency but only when the stationarity assumption of the disease incidence holds, i.e., the truncation distribution is uniform; otherwise they may generate biased estimates. In this paper, we propose a semi-parametric method for the Cox model under general left-truncation, where the truncation distribution is unspecified. Our approach is to make inference based on …

Preparedness Of Hospitals In The Republic Of Ireland For An Influenza Pandemic, An Infection Control Perspective, Mary Reidy, Fiona Ryan, Dervla Hogan, Seán Lacey, Claire Buckley

Department of Mathematics Publications

When an influenza pandemic occurs most of the population is susceptible and attack rates can range as high as 40–50 %. The most important failure in pandemic planning is the lack of standards or guidelines regarding what it means to be ‘prepared’. The aim of this study was to assess the preparedness of acute hospitals in the Republic of Ireland for an influenza pandemic from an infection control perspective.

A General Approach To Goodness Of Fit For U Processes, Debashis Ghosh, Youngjoo Cho

Debashis Ghosh

Goodness of fit procedures are essential tools for assessing model adequacy in statistics. In this work, we present a general theory and approach to goodness of fit techniques based on U-processes for the accelerated failure time (AFT) model. Many of the examples will focus on U-statistics of order 2. While many authors have proposed goodness of fit tests for U-statistics of order one, less has been developed for higher order U-statistics. In this paper, we propose goodness of fit tests for U-statistics of order 2 by using theoretical results from Nolan and Pollard (1987) and Nolan and Pollard (1988). We …

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 …

The Association Between The Il-1 Pathway, Isaac C. Wun

Dissertations & Theses (Open Access)

Cutaneous malignant melanoma (CMM) is a potentially lethal malignancy that warrants attention and further research, as it is known to that there is an increasing rate of incidence in theUnited States, and it is also known that exposure to UV light is its most crucial risk factor, and family history of melanoma is also an important risk factor. Melanoma is an aggressive and lethal cancer in humans. There are an estimated new 132,000 melanoma cases annually worldwide, and the trend has doubled in the past 20 years. However, attempts to treat melanoma have encountered considerable resistance and remained ineffective. The …

Native Insect Herbivory Limits Population Growth Rate Of A Non-Native Thistle, James O. Eckberg, Brigitte Tenhumberg, Svata M. Louda

Brigitte Tenhumberg Papers

The influence of native fauna on non-native plant population growth, size, and distribution is not well documented. Previous studies have shown that native insects associated with tall thistle (Cirsium altissimum) also feed on the leaves, stems, and flower heads of the Eurasian congener Cirsium vulgare, thus limiting individual plant performance. In this study, we tested the effects of insect herbivores on the population growth rate of C. vulgare. We experimentally initiated invasions by adding seeds at four unoccupied grassland sites in eastern Nebraska, USA, and recorded plant establishment, survival, and reproduction. Cumulative foliage and floral herbivory …

The Use Of Propensity Score Methods With Survival Or Time-To-Event Outcomes: Reporting Measures Of Effect Similar To Those Used In Randomized Experiments, Peter C. Austin

Peter Austin

Propensity score methods are increasingly being used to estimate causal treatment effects in observational studies. In medical and epidemiological studies, outcomes are frequently time-to-event in nature. Propensity-score methods are often applied incorrectly when estimating the effect of treatment on time-to-event outcomes. This article describes how two different propensity score methods (matching and inverse probability of treatment weighting) can be used to estimate the measures of effect that are frequently reported in randomized controlled trials: (i) marginal survival curves, which describe survival in the population if all subjects were treated or if all subjects were untreated; and (ii) marginal hazard ratios. …

The Performance Of Different Propensity Score Methods For Estimating Absolute Effects Of Treatments On Survival Outcomes: A Simulation Study, Peter C. Austin

Peter Austin

Observational studies are increasingly being used to estimate the effect of treatments, interventions and exposures on outcomes that can occur over time. Historically, the hazard ratio, which is a relative measure of effect, has been reported. However, medical decision making is best informed when both relative and absolute measures of effect are reported. When outcomes are time-to-event in nature, the effect of treatment can also be quantified as the change in mean or median survival time due to treatment and the absolute reduction in the probability of the occurrence of an event within a specified duration of follow-up. We describe …

Flexible Partially Linear Single Index Regression Models For Multivariate Survival Data, Na Lei

Electronic Thesis and Dissertation Repository

Survival regression models usually assume that covariate effects have a linear form. In many circumstances, however, the assumption of linearity may be violated. The present work addresses this limitation by adding nonlinear covariate effects to survival models. Nonlinear covariates are handled using a single index structure, which allows high-dimensional nonlinear effects to be reduced to a scalar term. The nonlinear single index approach is applied to modeling of survival data with multivariate responses, in three popular models: the proportional hazards (PH) model, the proportional odds (PO) model, and the generalized transformation model. Another extension of the PH and PO model …

Statistical Inference For Data Adaptive Target Parameters, Mark J. Van Der Laan, Alan E. Hubbard, Sara Kherad Pajouh

U.C. Berkeley Division of Biostatistics Working Paper Series

Consider one observes n i.i.d. copies of a random variable with a probability distribution that is known to be an element of a particular statistical model. In order to define our statistical target we partition the sample in V equal size sub-samples, and use this partitioning to define V splits in estimation-sample (one of the V subsamples) and corresponding complementary parameter-generating sample that is used to generate a target parameter. For each of the V parameter-generating samples, we apply an algorithm that maps the sample in a target parameter mapping which represent the statistical target parameter generated by that parameter-generating …

Targeted Maximum Likelihood Estimation For Dynamic And Static Longitudinal Marginal Structural Working Models, Maya L. Petersen, Joshua Schwab, Susan Gruber, Nello Blaser, Michael Schomaker, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

This paper describes a targeted maximum likelihood estimator (TMLE) for the parameters of longitudinal static and dynamic marginal structural models. We consider a longitudinal data structure consisting of baseline covariates, time-dependent intervention nodes, intermediate time-dependent covariates, and a possibly time dependent outcome. The intervention nodes at each time point can include a binary treatment as well as a right-censoring indicator. Given a class of dynamic or static interventions, a marginal structural model is used to model the mean of the intervention specific counterfactual outcome as a function of the intervention, time point, and possibly a subset of baseline covariates. Because …

Integrative Analysis Of Prognosis Data On Multiple Cancer Subtypes, Shuangge Ma

Shuangge Ma

In cancer research, profiling studies have been extensively conducted, searching for genes/SNPs associated with prognosis. Cancer is diverse. Examining similarity and difference in the genetic basis of multiple subtypes of the same cancer can lead to a better understanding of their connections and distinctions. Classic meta-analysis methods analyze each subtype separately and then compare analysis results across subtypes. Integrative analysis methods, in contrast, analyze the raw data on multiple subtypes simultaneously and can outperform meta-analysis methods. In this study, prognosis data on multiple subtypes of the same cancer are analyzed. An AFT (accelerated failure time) model is adopted to describe …

Evaluation Of The Survival Effect For Various Treatment Modalities Among Stage Ii And Iii Rectal Cancer Patients In California, 1994-2009, Myung Mi Cho

Loma Linda University Electronic Theses, Dissertations & Projects

Background: European trials evaluating the effect of preoperative (PreOP) versus postoperative chemoradiotherapy (PostOP CRT) found no survival benefit. However, the effect of a change from PostOP to PreOP CRT has not been evaluated in a population-based setting. We sought to evaluate multimodal treatment changes and overall survival for perioperative (PeriOP) CRT versus surgery alone and for PreOP versus PostOP CRT from 1994 through 2009 among patients receiving radical surgery for stage II and III rectal cancer (RC).

Patients and Methods: We conducted a nonconcurrent cohort study evaluating demographic predictors of multimodal therapy for stage II and III RC using …

An Analysis Of Risk Reduction Choices In Dcis Breast Cancer Patients, Lauren Soltesz

Statistics

The main focus of this paper was to evaluate possible demographic and clinical characteristics associated with a woman’s choice of breast conserving surgery (BCS), unilateral mastectomy (ULM), or bilateral risk reduction mastectomy (BRRM). The cohort consisted of patients presenting to the City of Hope National Medical Center with ductal carcinoma in situ breast cancer who elected to have cancer directed surgery (N=305). Analyses to examine associations of patient characteristics with type of surgery were conducted using a multinomial logistic regression. Results showed that older women were more likely to choose breast conserving surgery over bilateral risk reduction mastectomy than younger …

Incorporating Network Structure In Integrative Analysis Of Cancer Prognosis Data, Shuangge Ma

Shuangge Ma

In high-throughput cancer genomic studies, markers identified from the analysis of single datasets may have unsatisfactory properties because of low sample sizes. Integrative analysis pools and analyzes raw data from multiple studies, and can effectively increase sample size and lead to improved marker identification results. In this study, we consider the integrative analysis of multiple high-throughput cancer prognosis studies. In the existing integrative analysis studies, the interplay among genes, which can be described using the network structure, has not been effectively accounted for. In network analysis, tightly-connected nodes (genes) are more likely to have related biological functions and similar regression …

Risk Factors Of Follicular Lymphoma, Shuangge Ma

Shuangge Ma

No abstract provided.

Health Insurance Coverage And Impact: A Survey In Three Cities In China, Shuangge Ma

Shuangge Ma

No abstract provided.

Integrative Analysis Of Multiple Cancer Genomic Datasets Under The Heterogeneity Model, Shuangge Ma

Shuangge Ma

No abstract provided.

Health Insurance Coverage, Medical Expenditure And Coping Strategy: Evidence From Taiwan, Shuangge Ma

Shuangge Ma

No abstract provided.

Impact Of Illness And Medical Expenditure On Household Consumptions: A Survey In Western China, Shuangge Ma

Shuangge Ma

No abstract provided.

Identification Of Gene-Environment Interactions In Cancer Prognosis Studies Using Penalization, Shuangge Ma

Shuangge Ma

High-throughput cancer studies have been extensively conducted, searching for genetic risk factors independently associated with prognosis beyond clinical and environmental risk factors. Many studies have shown that the gene-environment interactions may have important implications. Some of the existing methods, such as the commonly adopted single-marker analysis, may be limited in that they cannot accommodate the joint effects of a large number of genetic markers or use ineffective marker identification techniques. In this study, we analyze cancer prognosis studies, and adopt the AFT (accelerated failure time) model to describe survival. A weighted least squares approach, which has the lowest computational cost, …

A Regularization Corrected Score Method For Nonlinear Regression Models With Covariate Error, David M. Zucker, Malka Gorfine, Yi Li, Donna Spiegelman

Harvard University Biostatistics Working Paper Series

No abstract provided.

Effectively Selecting A Target Population For A Future Comparative Study, Lihui Zhao, Lu Tian, Tianxi Cai, Brian Claggett, L. J. Wei

Harvard University Biostatistics Working Paper Series

When comparing a new treatment with a control in a randomized clinical study, the treatment effect is generally assessed by evaluating a summary measure over a specific study population. The success of the trial heavily depends on the choice of such a population. In this paper, we show a systematic, effective way to identify a promising population, for which the new treatment is expected to have a desired benefit, using the data from a current study involving similar comparator treatments. Specifically, with the existing data we first create a parametric scoring system using multiple covariates to estimate subject-specific treatment differences. …

Bayesian Phase I Dose Finding In Cancer Trials, Lin Yang

Dissertations & Theses (Open Access)

This dissertation explores phase I dose-finding designs in cancer trials from three perspectives: the alternative Bayesian dose-escalation rules, a design based on a time-to-dose-limiting toxicity (DLT) model, and a design based on a discrete-time multi-state (DTMS) model.

We list alternative Bayesian dose-escalation rules and perform a simulation study for the intra-rule and inter-rule comparisons based on two statistical models to identify the most appropriate rule under certain scenarios. We provide evidence that all the Bayesian rules outperform the traditional ``3+3'' design in the allocation of patients and selection of the maximum tolerated dose.

The design based on a time-to-DLT model …

On The Covariate-Adjusted Estimation For An Overall Treatment Difference With Data From A Randomized Comparative Clinical Trial, Lu Tian, Tianxi Cai, Lihui Zhao, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

Threshold Regression Models Adapted To Case-Control Studies, And The Risk Of Lung Cancer Due To Occupational Exposure To Asbestos In France, Antoine Chambaz, Dominique Choudat, Catherine Huber, Jean-Claude Pairon, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Asbestos has been known for many years as a powerful carcinogen. Our purpose is quantify the relationship between an occupational exposure to asbestos and an increase of the risk of lung cancer. Furthermore, we wish to tackle the very delicate question of the evaluation, in subjects suffering from a lung cancer, of how much the amount of exposure to asbestos explains the occurrence of the cancer. For this purpose, we rely on a recent French case-control study. We build a large collection of threshold regression models, data-adaptively select a better model in it by multi-fold likelihood-based cross-validation, then fit the …

Clustering With Exclusion Zones: Genomic Applications, Mark Segal, Yuanyuan Xiao, Fred Huffer

Mark R Segal

Methods for formally evaluating the clustering of events in space or time, notably the scan statistic, have been richly developed and widely applied. In order to utilize the scan statistic and related approaches, it is necessary to know the extent of the spatial or temporal domains wherein the events arise. Implicit in their usage is that these domains have no “holes”—hereafter “exclusion zones”—regions in which events a priori cannot occur. However, in many contexts, this requirement is not met. When the exclusion zones are known, it is straightforward to correct the scan statistic for their occurrence by simply adjusting the …

Survival Analysis Of Microarray Data With Microarray Measurement Subject To Measurement Error, Juan Xiong

Electronic Thesis and Dissertation Repository

Microarray technology is essentially a measurement tool for measuring expressions of genes, and this measurement is subject to measurement error. Gene expressions could be employed as predictors for patient survival, and the measurement error involved in the gene expression is often ignored in the analysis of microarray data in the literature. Efforts are needed to establish statistical method for analyzing microarray data without ignoring the error in gene expression. A typical microarray data set has a large number of genes far exceeding the sample size. Proper selection of survival relevant genes contributes to an accurate prediction model. We study the …

Landmark Prediction Of Survival, Layla Parast, Tianxi Cai

Harvard University Biostatistics Working Paper Series

No abstract provided.