Biostatistics Commons^™

A Global Partial Likelihood Estimator Of The Time-Varying Effects For Time-Dependent Treatment, Huazhen Lin, Zhe Fei, Yi Li

The University of Michigan Department of Biostatistics Working Paper Series

The timing of time-dependent treatment - e.g., when to perform kidney transplantation - is an important factor for evaluating treatment efficacy. A naive comparison between the treatment and nontreatment groups, while ignoring the timing of treatment, typically yields results that might biasedly favor the treatment group, as only patients who survive long enough will get treated. On the other hand, studying the effect of time-dependent treatment is often complex, as it involves modeling treatment history and accounting for the possible time-varying nature of the treatment effect. We propose a varying-coefficient Cox model that investigates the efficacy of time-dependent treatment by …

A Unification Of Mediation And Interaction: A Four-Way Decomposition, Tyler J. Vanderweele

Harvard University Biostatistics Working Paper Series

It is shown that the overall effect of an exposure on an outcome, in the presence of a mediator with which the exposure may interact, can be decomposed into four components: (i) the effect of the exposure in the absence of the mediator, (ii) the interactive effect when the mediator is left to what it would be in the absence of exposure, (iii) a mediated interaction, and (iv) a pure mediated effect. These four components, respectively, correspond to the portion of the effect that is due to neither mediation nor interaction, to just interaction (but not mediation), to both mediation …

Five Fundamental Gaps In Nature-Nurture Science, Peter J. Taylor

Working Papers on Science in a Changing World

Difficulties identifying causally relevant genetic variants underlying patterns of human variation have been given competing interpretations. The debate is illuminated in this article by drawing attention to the issue of underlying heterogeneity—the possibility that genetic and environmental factors or entities underlying a trait are heterogeneous—as well as four other fundamental gaps in the methods and interpretation of classical quantitative genetics: "Genetic" and "environmental" fractions of variation in traits are distinct from measurable genetic and environmental factors underlying the traits’ development; Standard formulas for partitioning variation in human traits are unreliable; Methods for translation from fractions of variation to measurable …

New Malignancies After Squamous Cell Carcinoma And Melanomas: A Population-Based Study From Norway, Trude E. Robsahm, Margaret R. Karagas, Judy R. Rees, Astri Syse

Dartmouth Scholarship

Skin cancer survivors experience an increased risk for subsequent malignancies but the associated risk factors are poorly understood. This study examined the risk of a new primary cancer following an initial skin cancer and assessed risk factors associated with second primary cancers.

Efficiently Identifying Failures Using Quantitative Tests, Matrix-Pooling And The Em-Algorithm, Brett Hanscom, Susanne May, Jim Hughes

UW Biostatistics Working Paper Series

Pooled-testing methods can greatly reduce the number of tests needed to identify failures in a collection of samples. Existing methodology has focused primarily on binary tests, but there is a clear need for improved efficiency when using expensive quantitative tests, such as tests for HIV viral load in resource-limited settings. We propose a matrix-pooling method which, based on pooled-test results, uses the EM algorithm to identify individual samples most likely to be failures. Two hundred datasets for each of a wide range of failure prevalence were simulated to test the method. When the measurement of interest was normally distributed, at …

A Predictive Enrichment Procedure To Identify Potential Responders To A New Therapy For Randomized, Comparative, Controlled Clinical Studies, Junlong Li, Lihui Zhao, Lu Tian, Tianxi Cai, Brian Claggett, Andrea Callegaro, Benjamin Dizier, Bart Spiessens, Fernando Ulloa-Montoya, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

The Association Of Calcium Intake And Other Risk Factors With Cardiovascular Disease Among Obese Adults In Usa, Yang Chen, Sheryl Strasser, Katie Callahan, David Blackley, Yan Cao, Liang Wang, Shimin Zheng

ETSU Faculty Works

In this study, we used a cross-sectional study design to examine the relationship between the calcium intake and risk factors for CVD among obese adults by using continuous waves of National Health and Nutrition Examination Survey (NHANES) data 1999-2010. The association between calcium intake and risk factors of CVD (hypertension, total cholesterol, HDL, glycohemoglobin), CRP, albuminuria) is assessed among obese adults in USA. The incidence of Cardiovascular Disease (CVD) is high among obese people. The potential effects of inadequate calcium intake on CVD are receiving increased epidemiologic attention. Understanding the association between risk factors for CVD and calcium intake among …

A Novel Three Serum Phospholipid Panel Differentiates Normal Individuals From Those With Prostate Cancer, Nima Patel, Robert L. Vogel, Kumar Chandra-Kuntal, Wayne Glasgow, Uddhav Kelavkar

Biostatistics: Faculty Publications

Background: The results of prostate specific antigen (PSA) and digital rectal examination (DRE) screenings lead to both under and over treatment of prostate cancer (PCa). As such, there is an urgent need for the identification and evaluation of new markers for early diagnosis and disease prognosis. Studies have shown a link between PCa, lipids and lipid metabolism. Therefore, the aim of this study was to examine the concentrations and distribution of serum lipids in patients with PCa as compared with serum from controls.

Method: Using Electrospray ionization mass spectrometry (ESI-MS/MS) lipid profiling, we analyzed serum phospholipids from age-matched subjects who …

Clustering Survival Outcomes Using Dirichlet Process Mixture, Lili Zhao, Jingchunzi Shi, Tempie H. Shearon, Yi Li

The University of Michigan Department of Biostatistics Working Paper Series

Motivated by the national evaluation of mortality rates at kidney transplant centers in the United States, we sought to assess transplant center long- term survival outcomes by applying a methodology developed in Bayesian non-parametrics literature. We described a Dirichlet process model and a Dirichlet process mixture model with a Half-Cauchy for the estimation of the risk- adjusted effects of the transplant centers. To improve the model performance and interpretability, we centered the Dirichlet process. We also proposed strategies to increase model's classification ability. Finally we derived statistical measures and created graphical tools to rate transplant centers and identify outlying centers …

Mediation Analysis With Time-Varying Exposures And Mediators, Tyler J. Vanderweele, Eric Tchetgen Tchetgen

Harvard University Biostatistics Working Paper Series

In this paper we consider mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are no time-varying confounders affected by prior exposure and mediator values, identification of direct and indirect effects is achieved by a longitudinal version of Pearl's mediation formula. When there are time-varying confounders affected …

A Phylogenetic Model For Understanding The Effect Of Gene Duplication On Cancer Progression, Qin Ma, Jaxk H. Reeves, David A. Liberles, Lili Yu, Zheng Chang, Jing Zhao, Juan Cui, Ying Xu, Liang Liu

Biostatistics: Faculty Publications

As biotechnology advances rapidly, a tremendous amount of cancer genetic data has become available, providing an unprecedented opportunity for understanding the genetic mechanisms of cancer. To understand the effects of duplications and deletions on cancer progression, two genomes (normal and tumor) were sequenced from each of five stomach cancer patients in different stages (I, II, III and IV). We developed a phylogenetic model for analyzing stomach cancer data. The model assumes that duplication and deletion occur in accordance with a continuous time Markov Chain along the branches of a phylogenetic tree attached with five extended branches leading to the tumor …

Regression Modeling Of Longitudinal Binary Outcomes With Outcome-Dependent Observation Times, Kay See Tan, Andrea B. Troxel, Stephen E. Kimmel, Kevin G. Volpp, Benjamin French

UPenn Biostatistics Working Papers

Conventional longitudinal data analysis methods assume that outcomes are independent of the data-collection schedule. However, the independence assumption may be violated, for example, when adverse events trigger additional physician visits in between prescheduled follow-ups. Observation times may therefore be associated with outcome values, which may introduce bias when estimating the eect of covariates on outcomes using standard longitudinal regression methods. Existing semi-parametric methods that accommodate outcome-dependent observation times are limited to the analysis of continuous outcomes. We develop new methods for the analysis of binary outcomes, while retaining the exibility of semi-parametric models. Our methods are based on counting process …

Bayesian Model Averaging:- An Application In Cancer Clinical Trial, Atanu Bhattacharjee

COBRA Preprint Series

Data driven conclusion is mostly accepted approach in any medical research problem. In case of limited knowledge of deep idea about supportive data on the problem, automatic digging of the variable plays important role for insight view of the study. Bayesian model averaging can be considered for automatics variable selection. It can be used as an alternative of stepwise regression method. The aim of this paper is to show the application of Bayesian modeling averaging in medical research particularly in cancer trial. Method is illustrated on Bone marrow transplant data. It can be recommended that BMA can be used frequently …

Strengthening Interactions Between Statisticians And Collaborators: Objectives And Sample Sizes, Emily Van Meter, Richard Charnigo

Biostatistics Faculty Publications

No abstract provided.

Adaptive Pair-Matching In The Search Trial And Estimation Of The Intervention Effect, Laura Balzer, Maya L. Petersen, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

In randomized trials, pair-matching is an intuitive design strategy to protect study validity and to potentially increase study power. In a common design, candidate units are identified, and their baseline characteristics used to create the best n/2 matched pairs. Within the resulting pairs, the intervention is randomized, and the outcomes measured at the end of follow-up. We consider this design to be adaptive, because the construction of the matched pairs depends on the baseline covariates of all candidate units. As consequence, the observed data cannot be considered as n/2 independent, identically distributed (i.i.d.) pairs of units, as current practice assumes. …

Concomitant Socioeconomic, Behavioral, And Biological Factors Associated With The Disproportionate Hiv Infection Burden Among Black Men Who Have Sex With Men In 6 U.S. Cities, Kenneth H. Mayer, Lei Wang, Beryl A. Koblin, Sharon B. Mannheimer, Manya Magnus, +13 Additional Authors

Epidemiology Faculty Publications

Background

American Black men who have sex with men (MSM) are disproportionately affected by HIV, but the factors associated with this concentrated epidemic are not fully understood.

Methods

Black MSM were enrolled in 6 US cities to evaluate a multi-component prevention intervention, with the current analysis focusing on the correlates of being newly diagnosed with HIV compared to being HIV-uninfected or previously diagnosed with HIV.

Results

HPTN 061 enrolled 1553 Black MSM whose median age was 40; 30% self-identified exclusively as gay or homosexual, 29% exclusively as bisexual, and 3% as transgender. About 1/6th(16.2%) were previously diagnosed with HIV (PD); …

A Joint Model For Multistate Disease Processes And Random Informative Observation Times, With Applications To Electronic Medical Records Data, Jane M. Lange, Rebecca A. Hubbard, Lurdes Y. T. Inoue, Vladimir Minin

UW Biostatistics Working Paper Series

Multistate models are used to characterize individuals' natural histories through diseases with discrete states. Observational data resources based on electronic medical records pose new opportunities for studying such diseases. However, these data consist of observations of the process at discrete sampling times, which may either be pre-scheduled and non-informative, or symptom-driven and informative about an individual's underlying disease status. We have developed a novel joint observation and disease transition model for this setting. The disease process is modeled according to a latent continuous time Markov chain; and the observation process, according to a Markov-modulated Poisson process with observation rates that …

Change Point Testing In Logistic Regression Models With Interaction Term, Youyi Fong, Chongzhi Di, Sallie Permar

UW Biostatistics Working Paper Series

The threshold effect takes place in situations where the relationship between an outcome variable and a predictor variable changes as the predictor value crosses a certain threshold/change point. Threshold effects are often plausible in a complex biological system, especially in defining immune responses that are protective against infections such as HIV-1, which motivates the current work. We study two hypothesis testing problems in change point models. We first compare three different approaches to obtaining a p-value for the maximum of scores test in a logistic regression model with change point variable as a main effect. Next, we study the testing …

Meta-Analysis Of Social-Personality Psychological Research, Blair T. Johnson, Alice H. Eagly

CHIP Documents

This publication provides a contemporary treatment of the subject of meta-analysis in relation to social-personality psychology. Meta-analysis literally refers to the statistical pooling of the results of independent studies on a given subject, although in practice it refers as well to other steps of research synthesis, including defining the question under investigation, gathering all available research reports, coding of information about the studies and their effects, and interpretation/dissemination of results. Discussed as well are the hallmarks of high-quality meta-analyses.

Extending Mendelian Risk Prediction Models To Handle Misreported Family History, Danielle Braun, Malka Gorfine, Hormuzd A. Katki, Argyrios Ziogas, Hoda Anton-Culver, Giovanni Parmigiani

Harvard University Biostatistics Working Paper Series

Mendelian risk prediction models calculate the probability of a proband being a mutation carrier based on family history and known mutation prevalence and penetrance. Family history in this setting, is self-reported and is often reported with error. Various studies in the literature have evaluated misreporting of family history. Using a validation data set which includes both error-prone self-reported family history and error-free validated family history, we propose a method to adjust for misreporting of family history. We estimate the measurement error process in a validation data set (from University of California at Irvine (UCI)) using nonparametric smoothed Kaplan-Meier estimators, and …

Nonparametric Adjustment For Measurement Error In Time To Event Data, Danielle Braun, Malka Gorfine, Hormuzd A. Katki, Argyrios Ziogas, Giovanni Parmigiani

Harvard University Biostatistics Working Paper Series

Measurement error in time to event data used as a predictor will lead to inaccurate predictions. This arises in the context of self-reported family history, a time to event predictor often measured with error, used in Mendelian risk prediction models. Using a validation data set, we propose a method to adjust for this type of measurement error. We estimate the measurement error process using a nonparametric smoothed Kaplan-Meier estimator, and use Monte Carlo integration to implement the adjustment. We apply our method to simulated data in the context of both Mendelian risk prediction models and multivariate survival prediction models, as …

Estimating Population Treatment Effects From A Survey Sub-Sample, Kara E. Rudolph, Ivan Diaz, Michael Rosenblum, Elizabeth A. Stuart

Johns Hopkins University, Dept. of Biostatistics Working Papers

We consider the problem of estimating an average treatment effect for a target population from a survey sub-sample. Our motivating example is generalizing a treatment effect estimated in a sub-sample of the National Comorbidity Survey Replication Adolescent Supplement to the population of U.S. adolescents. To address this problem, we evaluate easy-to-implement methods that account for both non-random treatment assignment and a non-random two-stage selection mechanism. We compare the performance of a Horvitz-Thompson estimator using inverse probability weighting (IPW) and two double robust estimators in a variety of scenarios. We demonstrate that the two double robust estimators generally outperform IPW in …

Set-Based Tests For Genetic Association In Longitudinal Studies, Zihuai He, Min Zhang, Seunggeun Lee, Jennifer A. Smith, Xiuqing Guo, Walter Palmas, Sharon L.R. Kardia, Ana V. Diez Roux, Bhramar Mukherjee

The University of Michigan Department of Biostatistics Working Paper Series

Genetic association studies with longitudinal markers of chronic diseases (e.g., blood pressure, body mass index) provide a valuable opportunity to explore how genetic variants affect traits over time by utilizing the full trajectory of longitudinal outcomes. Since these traits are likely influenced by the joint effect of multiple variants in a gene, a joint analysis of these variants considering linkage disequilibrium (LD) may help to explain additional phenotypic variation. In this article, we propose a longitudinal genetic random field model (LGRF), to test the association between a phenotype measured repeatedly during the course of an observational study and a set …

Analysis Of Schizophrenia Data Using A Nonlinear Threshold Index Logistic Model., Zhenyu Jiang, Chengan Du, Assen Jablensky, Hua Liang, Zudi Lu, Yang Ma, Kok Lay Teo

GW Biostatistics Center

Genetic information, such as single nucleotide polymorphism (SNP) data, has been widely recognized as useful in prediction of disease risk. However, how to model the genetic data that is often categorical in disease class prediction is complex and challenging. In this paper, we propose a novel class of nonlinear threshold index logistic models to deal with the complex, nonlinear effects of categorical/discrete SNP covariates for Schizophrenia class prediction. A maximum likelihood methodology is suggested to estimate the unknown parameters in the models. Simulation studies demonstrate that the proposed methodology works viably well for moderate-size samples. The suggested approach is therefore …

Mediation Analysis Of Gestational Age, Congenital Heart Defects, And Infant Birth-Weight, Adane Wogu, Christopher Loffredo, Ionut Bebu, George Luta

GW Biostatistics Center

Background

In this study we assessed the mediation role of the gestational age on the effect of the infant’s congenital heart defects (CHD) on birth-weight.

Methods

We used secondary data from the Baltimore-Washington Infant Study (1981–1989). Mediation analysis was employed to investigate whether gestational age acted as a mediator of the association between CHD and reduced birth-weight. We estimated the mediated effect, the mediation proportion, and their corresponding 95% confidence intervals (CI) using several methods.

Results

There were 3362 CHD cases and 3564 controls in the dataset with mean birth-weight of 3071 (SD = 729) and 3353 (SD = 603) …

Engagement With Care, Substance Use, And Adherence To Therapy In Hiv/Aids, Patrice K. Nicholas, Suzanne Willard, Clinton J. Thompson, Carol Dawson-Rose, Inge B. Corless, +20 Additional Authors

GW Biostatistics Center

Engagement with care for those living with HIV is aimed at establishing a strong relationship between patients and their health care provider and is often associated with greater adherence to therapy and treatment (Flickinger, Saha, Moore, and Beach, 2013). Substance use behaviors are linked with lower rates of engagement with care and medication adherence (Horvath, Carrico, Simoni, Boyer, Amico, and Petroli, 2013). This study is a secondary data analysis using a cross-sectional design from a larger randomized controlled trial (n = 775) that investigated the efficacy of a self-care symptom management manual for participants living with HIV. Participants were …

Short And Long-Term Lifestyle Coaching Approaches Used To Address Diverse Participant Barriers To Weight Loss And Physical Activity Adherence, Elizabeth M. Venditti, Judith Wylie-Rosett, Linda M. Delahanty, Lisa L. Mele, Mary A. Hoskin, Sharon Edelstein

GW Biostatistics Center

Background

Individual barriers to weight loss and physical activity goals in the Diabetes Prevention Program, a randomized trial with 3.2 years average treatment duration, have not been previously reported. Evaluating barriers and the lifestyle coaching approaches used to improve adherence in a large, diverse participant cohort can inform dissemination efforts.

Methods

Lifestyle coaches documented barriers and approaches after each session (mean session attendance = 50.3 +/- 21.8). Subjects were 1076 intensive lifestyle participants (mean age = 50.6 years; mean BMI = 33.9 kg/m2; 68% female, 48% non-Caucasian). Barriers and approaches used to improve adherence were ranked by the percentage of …

Cardiometabolic Risk Assessments By Body Mass Index Z-Score Or Waist-To-Height Ratio In A Multiethnic Sample Of Sixth-Graders, Henry S. Kahn, Laure El Ghormli, Russell Jago, Gary D. Foster, Robert G. Mcmurray, John B. Buse, Diane D. Stadler, Roberto P. Trevino, Tom Baranowski, Healthy Study Group

GW Biostatistics Center

Convention defines pediatric adiposity by the body mass index -score (BMIz) referenced to normative growth charts. Waist-to-height ratio (WHtR) does not depend on sex-and-age references. In the HEALTHY Study enrollment sample, we compared BMIz with WHtR for ability to identify adverse cardiometabolic risk. Among 5,482 sixth-grade students from 42 middle schools, we estimated explanatory variations (R²) and standardized beta coefficients of BMIz or WHtR for cardiometabolic risk factors: insulin resistance (HOMA-IR), lipids, blood pressures, and glucose. For each risk outcome variable, we prepared adjusted regression models for four subpopulations stratified by sex and high versus lower fatness. …

Community Colleges And Public Health: An Integral Part Of The Continuum Of Education For Public Health, Richard Riegelman, Cynthia Wilson

Epidemiology Faculty Publications

No abstract provided.

Hiv Testing Implementation In Two Urban Cities: Practice, Policy, And Perceived Barriers., Camden J Hallmark, Jennifer Skillicorn, Thomas P Giordano, Jessica A Davila, Marlene Mcneese, Nestor Rocha, Avemaria Smith, Stacey Cooper, Amanda D. Castel

Epidemiology Faculty Publications

BACKGROUND: Although funding has supported the scale up of routine, opt-out HIV testing in the US, variance in implementation mechanisms and barriers in high-burden jurisdictions remains unknown.

METHODS: We conducted a survey of health care organizations in Washington, DC and Houston/Harris County to determine number of HIV tests completed in 2011, policy and practices associated with HIV testing, funding mechanisms, and reported barriers to testing in each jurisdiction and to compare results between jurisdictions.

RESULTS: In 2012, 43 Houston and 35 DC HIV-testing organizations participated in the survey. Participants represented 85% of Department of Health-supported testers in DC and 90% …