Biostatistics Commons^™

Characteristics Associated With Willingness To Participate In A Randomized Controlled Behavioral Clinical Trial Using Home-Based Personal Computers And A Webcam, Hiroko H. Dodge, Yuriko Katsumata, Jian Zhu, Nora Mattek, Molly Bowman, Mattie Gregor, Katherine Wild, Jeffrey A Kaye

Biostatistics Faculty Publications

BACKGROUND: Trials aimed at preventing cognitive decline through cognitive stimulation among those with normal cognition or mild cognitive impairment are of significant importance in delaying the onset of dementia and reducing dementia prevalence. One challenge in these prevention trials is sample recruitment bias. Those willing to volunteer for these trials could be socially active, in relatively good health, and have high educational levels and cognitive function. These participants' characteristics could reduce the generalizability of study results and, more importantly, mask trial effects. We developed a randomized controlled trial to examine whether conversation-based cognitive stimulation delivered through personal computers, a webcam …

Can Acute Dermal Systemic Toxicity Tests Be Replaced With Oral Tests? A Comparison Of Route-Specific Systemic Toxicity And Hazard Classifications Under The Globally Harmonized System Of Classification And Labelling Of Chemicals (Ghs), Nigel P. Moore, David J. Andrew, Donald L. Bjerke, Stuart Creton, David Dreher, Thomas Holmes, Pilar Prieto, Troy Seidle, Tim G. Rowan

Troy Seidle, PhD

Acute systemic toxicity data (LD50 values) and hazard classifications derived in the rat following oral administration and dermal application have been analysed to examine whether or not orally-derived hazard classification or LD50 values can be used to determine dermal hazard classification. Comparing the oral and dermal classifications for 335 substances derived from oral and dermal LD50 values respectively revealed 17% concordance, and indicated that 7% of substances would be classified less severely while 76% would be classified more severely if oral classifications were applied directly to the dermal route. In contrast, applying the oral LD50 values within the dermal classification …

Statistical Inference For The Mean Outcome Under A Possibly Non-Unique Optimal Treatment Strategy, Alexander R. Luedtke, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

We consider challenges that arise in the estimation of the value of an optimal individualized treatment strategy defined as the treatment rule that maximizes the population mean outcome, where the candidate treatment rules are restricted to depend on baseline covariates. We prove a necessary and sufficient condition for the pathwise differentiability of the optimal value, a key condition needed to develop a regular asymptotically linear (RAL) estimator of this parameter. The stated condition is slightly more general than the previous condition implied in the literature. We then describe an approach to obtain root-n rate confidence intervals for the optimal value …

Mediation Analysis Of Gestational Age, Congenital Heart Defects, And Infant Birth-Weight, Adane F. Wogu, Christopher A. 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) …

A More Efficient Nonparametric Test Of Symmetry Based On Overlapping Coefficient, Hani M. Samawi, Robert L. Vogel

Biostatistics Faculty Publications

In this paper we provide a more efficient nonparametric test of symmetry based on the empirical overlap coefficient using kernel density estimation applied to an extreme order statistics, namely extreme ranked set sampling. Our simulation investigation reveals that our proposed test of symmetry is at least as powerful as currently available tests of symmetry. Intensive simulation is conducted to examine the power of the proposed test. An illustration is provided using cardiac output and body weight of neonates in a neonatal intensive care unit.

Methods For Identifying Regions Of Brain Activation Using Fmri Meta-Data, Meredith A. Ray

Theses and Dissertations

Functional neuroimaging is a relatively young discipline within the neurosciences that has led to significant advances in our understanding of the human brain and progress in neuroscientific research related to public health. Accurately identifying activated regions in the brain showing a strong association with an outcome of interest is crucial in terms of disease prediction and prevention. Functional magnetic resonance imaging (fMRI) is the most widely used method for this type of study as it has the ability to measure and identify the location of changes in tissue perfusion, blood oxygenation, and blood volume. In practice, the three-dimensional brain locations …

Simulation Based Evaluation Of Multiscale Small Area Health Models, Purbasha Dasgupta

Theses and Dissertations

The effects of scale on the analysis of spatial data, often referred to as the modifiable areal unit problem in spatial studies, is one of the issues often encountered in small area health models. These spatial effects of scale are also seen in the areas of disease mapping where data are usually available in counts. Often there is a need to consider the different scales of aggregation that exist within count data, since inferences based on analyses can vary if we change the definition of the unit of analysis. This thesis provides a framework that describes the distribution of relative …

Access To Hiv Prevention And Care For Hiv-Exposed And Hiv-Infected Children: A Qualitative Study In Rural And Urban Mozambique, Caroline De Schacht, Carlota Lucas, Caterina Mboa, Michelle Gill, Eugenia Macasse, Stelio A. Dimande, Emily A. Bobrow, Laura Guay

Epidemiology Faculty Publications

Background Follow-up of HIV-exposed children for the delivery of prevention of mother-to-child transmission services and for early diagnosis and treatment of HIV infection is critical to their survival. Despite efforts, uptake of postnatal care for these children remains low in many subSaharan African countries. Methods A qualitative study was conducted in three provinces in Mozambique to identify motivators and barriers to improve uptake of and retention in HIV prevention, care and treatment services for HIV-exposed and HIV-infected children. Participant recommendations were also gathered. Individual interviews (n=79) and focus group discussions (n=32) were conducted with parents/caregivers, grandmothers, community leaders and health …

Prognostic Value Of Lymphocyte Vascular Density And E-Cadherin In Inflammatory Breast Cancer, Paul H. Levine, Heather J. Hoffman, Audra Macneil, Salman Hashmi, Sherry X. Yang, Stephen Hewitt, Kenneth L. Van Golen, Sandra M. Swain

Epidemiology Faculty Publications

Background: We recently evaluated four laboratory assays, vascular endothelial growth factor D (VEGF-D), E-cadherin, lymphatic vessel density (LVD) measured by podoplanin, and intra-lymphatic tumor emboli (ILTE), which showed notable differences between inflammatory breast cancer (IBC) and non-inflammatory locally advanced breast cancer (LABC). In this study we investigated the potential of the three most quantitatively measured markers, E-cadherin, LVD and VEGF-D, to predict survival in the IBC patients.

Materials and Methods: This study involved the 100 cases identified in the Inflammatory Breast Cancer Registry (IBCR) whose tumors were previously evaluated for the four assays noted above. Living patients were recontacted and …

Identifying Change Points In A Covariate Effect On Time-To-Event Analysis With Reduced Isotonic Regression, Yong Ma, Yinglei Lai, John M. Lachin

GW Biostatistics Center

Isotonic regression is a useful tool to investigate the relationship between a quantitative covariate and a time-to-event outcome. The resulting non-parametric model is a monotonic step function of a covariate X and the steps can be viewed as change points in the underlying hazard function. However, when there are too many steps, over-fitting can occur and further reduction is desirable. We propose a reduced isotonic regression approach to allow combination of small neighboring steps that are not statistically significantly different. In this approach, a second stage, the reduction stage, is integrated into the usual monotonic step building algorithm by comparing …

Overview Of Inference About Roc Curve In Medical Diagnosis, Jingjing Yin

Biostatistics Faculty Publications

Medical diagnosis aims to identify diseased individuals through the evaluation of the measurements of some biomarkers by performing a diagnostic test based on some biomarker measurements. Biomarkers are measured on either discrete or continuous scale and continuous biomarkers are utilized more often in medical practice. This article introduces the most popular tool for evaluating continuous biomarkers: the Receiver Operating Characteristic (ROC) curve.

The Effectiveness Of Teleglaucoma Versus In-Patient Examination For Glaucoma Screening: A Systematic Review And Meta-Analysis, Sera-Melisa Thomas, Maya M Jeyaraman, Maya Jeyaraman, William G Hodge, Cindy Hutnik, John Costella, Monali S Malvankar-Mehta

Epidemiology and Biostatistics Publications

BACKGROUND: Glaucoma is the leading cause of irreversible visual impairment in the world affecting 60.5 million people worldwide in 2010, which is expected to increase to approximately 79.6 million by 2020. Therefore, glaucoma screening is important to detect, diagnose, and treat patients at the earlier stages to prevent disease progression and vision loss. Teleglaucoma uses stereoscopic digital imaging to take ocular images, which are transmitted electronically to an ocular specialist. The purpose is to synthesize literature to evaluate teleglaucoma, its diagnostic accuracy, healthcare system benefits, and cost-effectiveness.

METHODS: A systematic search was conducted to help locate published and unpublished studies. …

Assessing The Social And Ecological Factors That Influence Childhood Overweight And Obesity, Katie Callahan

Electronic Theses and Dissertations

The prevalence of childhood overweight and obesity is increasing at an alarming rate in the United States. Currently more than 1 in 3 children aged 2-19 are overweight or obese. This is of major concern because childhood overweight and obesity leads to chronic conditions such as type II diabetes and tracks into adulthood, where more severe adverse health outcomes arise. In this study I used the premise of the social ecological model (SEM) to analyze the common levels that a child is exposed to daily; the intrapersonal level, the interpersonal level, the school level, and the community level to better …

Quantifying An Adherence Path-Specific Effect Of Antiretroviral Therapy In The Nigeria Pepfar Program, Caleb Miles, Ilya Shpitser, Phyllis Kanki, Seema Meloni, Eric J. Tchetgen Tchetgen

Harvard University Biostatistics Working Paper Series

No abstract provided.

On The Restricted Mean Survival Time Curve Survival Analysis, Lihui Zhao, Brian Claggett, Lu Tian, Hajime Uno, Marc A. Pfeffer, Scott D. Solomon, Lorenzo Trippa, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Review Of Software For Analyzing Molecular Sequences, Haema Nilakanta, Kimberly L. Drews, Suzanne Firrell, Mary A. Foulkes, Kathleen A. Jablonski

GW Biostatistics Center

Background Over the past ten years, there has been an explosion of microbiome research. Many software packages for analyzing microbial sequences such as the 16S gene from 454 sequencers and Illumina platforms are available. But for a new researcher, it is difficult to know which package to choose. We present a systematic review of packages for the analysis of molecular sequences used to describe and compare microbial communities. This review gives students and researchers information to help choose the best analytic pipeline for their project. To the best of our knowledge, this is the first review of such software.

Findings …

Constrained Bayesian Estimation Of Inverse Probability Weights For Nonmonotone Missing Data, Baoluo Sun, Eric J. Tchetgen Tchetgen

Harvard University Biostatistics Working Paper Series

No abstract provided.

Testing Gene-Environment Interactions In The Presence Of Measurement Error, Chongzhi Di, Li Hsu, Charles Kooperberg, Alex Reiner, Ross Prentice

UW Biostatistics Working Paper Series

Complex diseases result from an interplay between genetic and environmental risk factors, and it is of great interest to study the gene-environment interaction (GxE) to understand the etiology of complex diseases. Recent developments in genetics field allows one to study GxE systematically. However, one difficulty with GxE arises from the fact that environmental exposures are often measured with error. In this paper, we focus on testing GxE when the environmental exposure E is subject to measurement error. Surprisingly, contrast to the well-established results that the naive test ignoring measurement error is valid in testing the main effects, we find that …

Personalized Evaluation Of Biomarker Value: A Cost-Benefit Perspective, Ying Huang, Eric Laber

UW Biostatistics Working Paper Series

For a patient who is facing a treatment decision, the added value of information provided by a biomarker depends on the individual patient’s expected response to treatment with and without the biomarker, as well as his/her tolerance of disease and treatment harm. However, individualized estimators of the value of a biomarker are lacking. We propose a new graphical tool named the subject-specific expected benefit curve for quantifying the personalized value of a biomarker in aiding a treatment decision. We develop semiparametric estimators for two general settings: i) when biomarker data are available from a randomized trial; and ii) when biomarker …

Data Analysis And Study Design In The Presence Of Error-Prone Diagnostic Tests, Xiangdong Gu

Doctoral Dissertations

Interval censored time to event outcomes arise when a silent event of interest is known to have occurred within a specific time period, determined by the times of the last negative and first positive diagnostic tests. The four chapters comprising this thesis are tied together by a common theme in that the outcome of interest is an interval censored time to event random variable. In Chapter 1, we describe a stratified Weibull model appropriate for interval cen- sored outcomes and implement a new R package straweib. We compare the proposed approach with the log-linear form of the Weibull regression model …

Identifying Genetic Variants For Heart Rate Variability In The Acetylcholine Pathway, Harriëtte Riese, Loretto M. Muñoz, Catharina A. Hartman, Xiuhua Ding, Shaoyong Su, Albertine J. Oldehinkel, Arie M. Van Roon, Peter J. Van Der Most, Joop Lefrandt, Ron T. Gansevoort, Pim Van Der Harst, Niek Verweij, Carmilla M. M. Licht, Dorret I. Boomsma, Jouke-Jan Hottenga, Gonneke Willemsen, Brenda W. J. H. Penninx, Ilja M. Nolte, Eco J. C. De Geus, Xiaoling Wang, Harold Snieder

Biostatistics Faculty Publications

Heart rate variability is an important risk factor for cardiovascular disease and all-cause mortality. The acetylcholine pathway plays a key role in explaining heart rate variability in humans. We assessed whether 443 genotyped and imputed common genetic variants in eight key genes (CHAT, SLC18A3, SLC5A7, CHRNB4, CHRNA3, CHRNA, CHRM2 and ACHE) of the acetylcholine pathway were associated with variation in an established measure of heart rate variability reflecting parasympathetic control of the heart rhythm, the root mean square of successive differences (RMSSD) of normal RR intervals. The association was studied in a …

Estimating Prevalence From Complex Surveys, Sophie O'Brien

Masters Theses

Massachusetts passed legislation in the fall of 2012 to allow the construction of three casinos and a slot parlor in the state. The prevalence of problem gambling in the state and in areas where casinos will be constructed is of particular interest. The goal is to evaluate the change in prevalence after construction of the casinos, using a multi-mode address based sample survey. The objective of this thesis is to evaluate and describe ways of using statistical inference to estimates prevalence rates in finite populations. Four methods were considered in an attempt to evaluate the prevalence of problem gambling in …

Cross-Design Synthesis For Extending The Applicability Of Trial Evidence When Treatment Effect Is Heterogeneous-I. Methodology, Ravi Varadhan, Carlos Weiss

Johns Hopkins University, Dept. of Biostatistics Working Papers

Randomized controlled trials (RCTs) provide reliable evidence for approval of new treatments, informing clinical practice, and coverage decisions. The participants in RCTs are often not a representative sample of the larger at-risk population. Hence it is argued that the average treatment effect from the trial is not generalizable to the larger at-risk population. An essential premise of this argument is that there is significant heterogeneity in the treatment effect (HTE). We present a new method to extrapolate the treatment effect from a trial to a target group that is inadequately represented in the trial, when HTE is present. Our method …

Cross-Design Synthesis For Extending The Applicability Of Trial Evidence When Treatment Effect Is Heterogeneous. Part Ii. Application And External Validation, Carlos Weiss, Ravi Varadhan

Johns Hopkins University, Dept. of Biostatistics Working Papers

Randomized controlled trials (RCTs) generally provide the most reliable evidence. When participants in RCTs are selected with respect to characteristics that are potential treatment effect modifiers, the average treatment effect from the trials may not be applicable to a specific target population. We present a new method to project the treatment effect from a RCT to a target group that is inadequately represented in the trial when there is heterogeneity in the treatment effect (HTE). The method integrates RCT and observational data through cross-design synthesis. An essential component is to identify HTE and a calibration factor for unmeasured confounding for …

Trends In The Prevalence And Mortality Of Cognitive Impairment In The United States: Is There Evidence Of A Compression Of Cognitive Morbidity, Kenneth Langa, Eric Larson, Jason Karlawish, David Cutler, Mohammed Kabeto, Scott Kim, Allison Rosen

Jason Karlawish

BACKGROUND: Recent medical, demographic, and social trends might have had an important impact on the cognitive health of older adults. To assess the impact of these multiple trends, we compared the prevalence and 2-year mortality of cognitive impairment (CI) consistent with dementia in the United States in 1993 to 1995 and 2002 to 2004. METHODS: We used data from the Health and Retirement Study (HRS), a nationally representative population-based longitudinal survey of U.S. adults. Individuals aged 70 years or older from the 1993 (N = 7,406) and 2002 (N = 7,104) waves of the HRS were included. CI was determined …

Enhanced Precision In The Analysis Of Randomized Trials With Ordinal Outcomes, Iván Díaz, Elizabeth Colantuoni, Michael Rosenblum

Johns Hopkins University, Dept. of Biostatistics Working Papers

We present a general method for estimating the effect of a treatment on an ordinal outcome in randomized trials. The method is robust in that it does not rely on the proportional odds assumption. Our estimator leverages information in prognostic baseline variables, and has all of the following properties: (i) it is consistent; (ii) it is locally efficient; (iii) it is guaranteed to match or improve the precision of the standard, unadjusted estimator. To the best of our knowledge, this is the first estimator of the causal relation between a treatment and an ordinal outcome to satisfy these properties. We …

Applications Of The Wei-Lachin Multivariate One-Sided Test For Multiple Outcomes On Possibly Different Scales, John M. Lachin

GW Biostatistics Center

Many studies aim to assess whether a therapy has a beneficial effect on multiple outcomes simultaneously relative to a control. Often the joint null hypothesis of no difference for the set of outcomes is tested using separate tests with a correction for multiple tests, or using a multivariate T2-like MANOVA or global test. However, a more powerful test in this case is a multivariate one-sided or one-directional test directed at detecting a simultaneous beneficial treatment effect on each outcome, though not necessarily of the same magnitude. The Wei-Lachin test is a simple 1 df test obtained from a simple …

Optimal Bayesian Adaptive Trials When Treatment Efficacy Depends On Biomarkers, Yifan Zhang, Lorenzo Trippa, Giovanni Parmigiani

Harvard University Biostatistics Working Paper Series

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% …

Generalized Quantile Treatment Effect, Sergio Venturini, Francesca Dominici, Giovanni Parmigiani

Harvard University Biostatistics Working Paper Series

No abstract provided.