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Evaluation Of Progress Towards The Unaids 90-90-90 Hiv Care Cascade: A Description Of Statistical Methods Used In An Interim Analysis Of The Intervention Communities In The Search Study, Laura Balzer, Joshua Schwab, Mark J. van der Laan, Maya L. Petersen 2017 Department of Biostatistics, Harvard T.H. Chan School of Public Heath

Evaluation Of Progress Towards The Unaids 90-90-90 Hiv Care Cascade: A Description Of Statistical Methods Used In An Interim Analysis Of The Intervention Communities In The Search Study, Laura Balzer, Joshua Schwab, Mark J. Van Der Laan, Maya L. Petersen

U.C. Berkeley Division of Biostatistics Working Paper Series

WHO guidelines call for universal antiretroviral treatment, and UNAIDS has set a global target to virally suppress most HIV-positive individuals. Accurate estimates of population-level coverage at each step of the HIV care cascade (testing, treatment, and viral suppression) are needed to assess the effectiveness of "test and treat" strategies implemented to achieve this goal. The data available to inform such estimates, however, are susceptible to informative missingness: the number of HIV-positive individuals in a population is unknown; individuals tested for HIV may not be representative of those whom a testing intervention fails to reach, and HIV-positive individuals with a viral ...


Calculating Power By Bootstrap, With An Application To Cluster-Randomized Trials, Ken Kleinman, Susan S. Huang 2017 University of Massachusetts Amherst, School of Public Health and Health Sciences

Calculating Power By Bootstrap, With An Application To Cluster-Randomized Trials, Ken Kleinman, Susan S. Huang

eGEMs (Generating Evidence & Methods to improve patient outcomes)

Background: A key requirement for a useful power calculation is that the calculation mimic the data analysis that will be performed on the actual data, once it is observed. Close approximations may be difficult to achieve using analytic solutions, however, and thus Monte Carlo approaches, including both simulation and bootstrap resampling, are often attractive. One setting in which this is particularly true is cluster-randomized trial designs. However, Monte Carlo approaches are useful in many additional settings as well. Calculating power for cluster-randomized trials using analytic or simulation-based methods is frequently unsatisfactory due to the complexity of the data analysis methods ...


It's All About Balance: Propensity Score Matching In The Context Of Complex Survey Data, David Lenis, Trang Q. ;Nguyen, Nian Dong, Elizabeth A. Stuart 2017 Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health

It's All About Balance: Propensity Score Matching In The Context Of Complex Survey Data, David Lenis, Trang Q. ;Nguyen, Nian Dong, Elizabeth A. Stuart

Johns Hopkins University, Dept. of Biostatistics Working Papers

Many research studies aim to draw causal inferences using data from large, nationally representative survey samples, and many of these studies use propensity score matching to make those causal inferences as rigorous as possible given the non-experimental nature of the data. However, very few applied studies are careful about incorporating the survey design with the propensity score analysis, which may mean that the results don’t generate population inferences. This may be because few methodological studies examine how to best combine these methods. Furthermore, even fewer of the methodological studies incorporate different non-response mechanisms in their analysis. This study examines ...


The Battle Against Malaria: A Teachable Moment, Randy K. Schwartz 2017 Schoolcraft College

The Battle Against Malaria: A Teachable Moment, Randy K. Schwartz

Journal of Humanistic Mathematics

Malaria has been humanity’s worst public health problem throughout recorded history. Mathematical methods are needed to understand which factors are relevant to the disease and to develop counter-measures against it. This article and the accompanying exercises provide examples of those methods for use in lower- or upper-level courses dealing with probability, statistics, or population modeling. These can be used to illustrate such concepts as correlation, causation, conditional probability, and independence. The article explains how the apparent link between sickle cell trait and resistance to malaria was first verified in Uganda using the chi-squared probability distribution. It goes on to ...


Estimating The Probability Of Clonal Relatedness Of Pairs Of Tumors In Cancer Patients, Audrey Mauguen, Venkatraman E. Seshan, Irina Ostrovnaya, Colin B. Begg 2017 Memorial Sloan-Kettering Cancer Center

Estimating The Probability Of Clonal Relatedness Of Pairs Of Tumors In Cancer Patients, Audrey Mauguen, Venkatraman E. Seshan, Irina Ostrovnaya, Colin B. Begg

Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series

Next generation sequencing panels are being used increasingly in cancer research to study tumor evolution. A specific statistical challenge is to compare the mutational profiles in different tumors from a patient to determine the strength of evidence that the tumors are clonally related, i.e. derived from a single, founder clonal cell. The presence of identical mutations in each tumor provides evidence of clonal relatedness, although the strength of evidence from a match is related to how commonly the mutation is seen in the tumor type under investigation. This evidence must be weighed against the evidence in favor of independent ...


Predicting Future Years Of Life, Health, And Functional Ability: A Healthy Life Calculator For Older Adults, Paula Diehr, Michael Diehr, Alice M. Arnold, Laura Yee, Michelle C. Odden, Calvin H. Hirsch, Stephen Thielke, Bruce Psaty, W Craig Johnson, Jorge Kizer, Anne B. Newman 2017 University of Washington

Predicting Future Years Of Life, Health, And Functional Ability: A Healthy Life Calculator For Older Adults, Paula Diehr, Michael Diehr, Alice M. Arnold, Laura Yee, Michelle C. Odden, Calvin H. Hirsch, Stephen Thielke, Bruce Psaty, W Craig Johnson, Jorge Kizer, Anne B. Newman

UW Biostatistics Working Paper Series

Introduction

Planning for the future would be easier if we knew how long we will live and, more importantly, how many years we will be healthy and able to enjoy it. There are few well-documented aids for predicting our future health. We attempted to meet this need for persons 65 years of age and older.

Methods

Data came from the Cardiovascular Health Study, a large longitudinal study of older adults that began in 1990. Years of life (YOL) were defined by measuring time to death. Years of healthy life (YHL) were defined by an annual question about self-rated health, and ...


Quantifying The Totality Of Treatment Effect With Multiple Event-Time Observations In The Presence Of A Terminal Event From A Comparative Clinical Study, Brian Claggett, Lu Tian, Haoda Fu, Scott D. Solomon, L. J. Wei 2017 Harvard Medical School

Quantifying The Totality Of Treatment Effect With Multiple Event-Time Observations In The Presence Of A Terminal Event From A Comparative Clinical Study, Brian Claggett, Lu Tian, Haoda Fu, Scott D. Solomon, L. J. Wei

Harvard University Biostatistics Working Paper Series

To evaluate the totality of one treatment's benefit/risk profile relative to an alternative treatment via a longitudinal comparative clinical study, the timing and occurrence of multiple clinical events are typically collected during the patient's followup. These multiple observations reflect the patient's disease progression/burden over time. The standard practice is to create a composite endpoint from the multiple outcomes, the timing of the occurrence of the first clinical event, to evaluate the treatment via the standard survival analysis techniques. By ignoring all events after the composite outcome, this type of assessment may not be ideal. Various ...


Mediation Analysis For Censored Survival Data Under An Accelerated Failure Time Model, Isabel Fulcher, Eric J. Tchetgen Tchetgen, Paige Williams 2017 Harvard University

Mediation Analysis For Censored Survival Data Under An Accelerated Failure Time Model, Isabel Fulcher, Eric J. Tchetgen Tchetgen, Paige Williams

Harvard University Biostatistics Working Paper Series

Recent advances in causal mediation analysis have formalized conditions for estimating direct and indirect effects in various contexts. These approaches have been extended to a number of models for survival outcomes including accelerated failure time (AFT) models which are widely used in a broad range of health applications given their intuitive interpretation. In this setting, it has been suggested that under standard assumptions, the “difference” and “product” methods produce equivalent estimates of the indirect effect of exposure on the survival outcome. We formally show that these two methods may produce substantially different estimates in the presence of censoring or truncation ...


Gender Differences In Hiv Care Among Criminal Justice-Involved Persons: Baseline Data From The Care+ Corrections Study., Curt Beckwith, Breana Uhrig Castonguay, Claudia Trezza, Lauri Bazerman, Rudy Patrick, Alice Cates, Halli Olsen, Ann Kurth, Tao Liu, James Peterson, Irene Kuo 2017 George Washington University

Gender Differences In Hiv Care Among Criminal Justice-Involved Persons: Baseline Data From The Care+ Corrections Study., Curt Beckwith, Breana Uhrig Castonguay, Claudia Trezza, Lauri Bazerman, Rudy Patrick, Alice Cates, Halli Olsen, Ann Kurth, Tao Liu, James Peterson, Irene Kuo

Epidemiology and Biostatistics Faculty Publications

BACKGROUND: HIV-infected individuals recently released from incarceration have suboptimal linkage and engagement in community HIV care. We conducted a study to evaluate an information and communication technology intervention to increase linkage to community care among HIV-infected persons recently involved in the criminal justice (CJ) system. Baseline characteristics including risk behaviors and HIV care indicators are reported and stratified by gender.

METHODS: We recruited HIV-infected individuals in the District of Columbia jail and persons with a recent history of incarceration through community and street outreach. Participants completed a baseline computer-assisted personal interview regarding HIV care and antiretroviral treatment (ART) adherence, substance ...


Detecting Discordance Enrichment Among A Series Of Two-Sample Genome-Wide Expression Data Sets, Yinglei Lai, Fanni Zhang, Tapan Nayak, Reza Modarres, Norman H. Lee, Timothy A. McCaffrey 2017 George Washington University

Detecting Discordance Enrichment Among A Series Of Two-Sample Genome-Wide Expression Data Sets, Yinglei Lai, Fanni Zhang, Tapan Nayak, Reza Modarres, Norman H. Lee, Timothy A. Mccaffrey

Epidemiology and Biostatistics Faculty Publications

Background

With the current microarray and RNA-seq technologies, two-sample genome-wide expression data have been widely collected in biological and medical studies. The related differential expression analysis and gene set enrichment analysis have been frequently conducted. Integrative analysis can be conducted when multiple data sets are available. In practice, discordant molecular behaviors among a series of data sets can be of biological and clinical interest.

Methods

In this study, a statistical method is proposed for detecting discordance gene set enrichment. Our method is based on a two-level multivariate normal mixture model. It is statistically efficient with linearly increased parameter space when ...


Risk Of Gastrointestinal Bleeding Among Dabigatran Users – A Self Controlled Case Series Analysis, Wenze Tang, Hsien-Yen Chang, Meijia Zhou, Sonal Singh 2017 George Washington University

Risk Of Gastrointestinal Bleeding Among Dabigatran Users – A Self Controlled Case Series Analysis, Wenze Tang, Hsien-Yen Chang, Meijia Zhou, Sonal Singh

Epidemiology and Biostatistics Faculty Publications

This article aims to evaluate the real world risk of gastrointestinal bleeding among users naïve to dabigatran. We adopted a self-controlled case series design. We sampled 1215 eligible adult participants who were continuous insured users between July 1, 2010 and March 31, 2012 with use of dabigatran and at least one gastrointestinal bleeding episode. We used a conditional Poisson regression to estimate incidence rate ratios. The population consisted of 64.69% of male and 60.25% patients equal to or greater than age 65 at start of observation. After adjustment for time-variant confounders, the incidence rate of gastrointestinal bleeding was ...


Post-Diagnosis Body Mass Index And Mortality Among Women Diagnosed With Endometrial Cancer: Results From The Women's Health Initiative., Hannah Arem, Ruth M Pfeiffer, Steven C Moore, Melinda L Irwin, Michael J LaMonte, Gloria E Sarto, Rami Nassir, Juhua Luo, Rowan T Chlebowski, Louise A Brinton, Charles E Matthews 2017 George Washington University

Post-Diagnosis Body Mass Index And Mortality Among Women Diagnosed With Endometrial Cancer: Results From The Women's Health Initiative., Hannah Arem, Ruth M Pfeiffer, Steven C Moore, Melinda L Irwin, Michael J Lamonte, Gloria E Sarto, Rami Nassir, Juhua Luo, Rowan T Chlebowski, Louise A Brinton, Charles E Matthews

Epidemiology and Biostatistics Faculty Publications

Higher body mass index (BMI) measured before endometrial cancer diagnosis has been associated with greater risk of developing endometrial cancer and higher mortality, but the association between BMI measured after diagnosis and mortality risk is unclear. We identified 467 women (91 deaths) in the Women's Health Initiative (WHI) with information on BMI measured after diagnosis and used Cox proportional hazards regression to generate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality. Comparing BMI 35+ with/m2, we observed no association with all-cause mortality (HR = 1.02, 95% CI 0.55-1.91). Our study does not support ...


Pointwise Influence Matrices For Functional-Response Regression, Philip T. Reiss, Lei Huang, Pei-Shien Wu, Huaihou Chen, Stan Colcombe 2016 New York University School of Medicine

Pointwise Influence Matrices For Functional-Response Regression, Philip T. Reiss, Lei Huang, Pei-Shien Wu, Huaihou Chen, Stan Colcombe

Philip T. Reiss

We extend the notion of an influence or hat matrix to regression with functional responses and scalar predictors. For responses depending linearly on a set of predictors, our definition is shown to reduce to the conventional influence matrix for linear models. The pointwise degrees of freedom, the trace of the pointwise hat matrix, are shown to have an adaptivity property that motivates a two-step bivariate smoother for modeling nonlinear dependence on a single predictor. This procedure adapts to varying complexity of the nonlinear model at different locations along the function, and thereby achieves better performance than competing tensor product smoothers ...


Novel Models Of Visual Topographic Map Alignment In The Superior Colliculus., Ruben A Tikidji-Hamburyan, Tarek A El-Ghazawi, Jason W. Triplett 2016 George Washington University

Novel Models Of Visual Topographic Map Alignment In The Superior Colliculus., Ruben A Tikidji-Hamburyan, Tarek A El-Ghazawi, Jason W. Triplett

Pediatrics Faculty Publications

The establishment of precise neuronal connectivity during development is critical for sensing the external environment and informing appropriate behavioral responses. In the visual system, many connections are organized topographically, which preserves the spatial order of the visual scene. The superior colliculus (SC) is a midbrain nucleus that integrates visual inputs from the retina and primary visual cortex (V1) to regulate goal-directed eye movements. In the SC, topographically organized inputs from the retina and V1 must be aligned to facilitate integration. Previously, we showed that retinal input instructs the alignment of V1 inputs in the SC in a manner dependent on ...


Dealing With Zero-Numerators In Estimating Drug-Dependence Chances: A Bayesian Approach, Olga A. Vsevolozhskaya, Fernando A. Wagner, James C. Anthony 2016 University of Kentucky

Dealing With Zero-Numerators In Estimating Drug-Dependence Chances: A Bayesian Approach, Olga A. Vsevolozhskaya, Fernando A. Wagner, James C. Anthony

Olga A. Vsevolozhskaya

Aims: At CPDD 2015, we applied parametric Hill functions to estimate the probability of drug dependence in relation to the duration of drug-taking experience. A problem we and others have encountered in the estimation of risk of becoming a drug dependence case is an observed point estimate of zero – the so-called “zero-numerator problem.” This problem can be easily observed in certain low risk subgroups even when the sample is large (e.g., the incidence of heroin dependence among 12 year old newly incident heroin users) or with small subgroup sample sizes. In these instances, tan observed zero point estimate does ...


The Moral Significance Of Indetectable Effects, Sven Ove Hansson 2016 University of New Hampshire

The Moral Significance Of Indetectable Effects, Sven Ove Hansson

RISK: Health, Safety & Environment

A reassessment of Parfit's fifth "mistake in moral mathematics."


Improving Power In Group Sequential, Randomized Trials By Adjusting For Prognostic Baseline Variables And Short-Term Outcomes, Tianchen Qian, Michael Rosenblum, Huitong Qiu 2016 Departmnet of Biostatistics, Johns Hopkins Bloomberg School of Public Health

Improving Power In Group Sequential, Randomized Trials By Adjusting For Prognostic Baseline Variables And Short-Term Outcomes, Tianchen Qian, Michael Rosenblum, Huitong Qiu

Johns Hopkins University, Dept. of Biostatistics Working Papers

In group sequential designs, adjusting for baseline variables and short-term outcomes can lead to increased power and reduced sample size. We derive formulas for the precision gain from such variable adjustment using semiparametric estimators for the average treatment effect, and give new results on what conditions lead to substantial power gains and sample size reductions. The formulas reveal how the impact of prognostic variables on the precision gain is modified by the number of pipeline participants, analysis timing, enrollment rate, and treatment effect heterogeneity, when the semiparametric estimator uses correctly specified models. Given set prognostic value of baseline variables and ...


An Examination Of The Neural Unreliability Thesis Of Autism, John Butler, Sophie Molholm, Gizely Andrade, John J. Foxe 2016 Dublin Institute of Technology

An Examination Of The Neural Unreliability Thesis Of Autism, John Butler, Sophie Molholm, Gizely Andrade, John J. Foxe

Articles

An emerging neuropathological theory of Autism, referred to here as “the neural unreliability thesis,” proposes greater variability in moment-to-moment cortical representation of environmental events, such that the system shows general instability in its impulse response function. Leading evidence for this thesis derives from functional neuroimaging, a methodology ill-suited for detailed assessment of sensory transmission dynamics occurring at the millisecond scale. Electrophysiological assessments of this thesis, however, are sparse and unconvincing. We conducted detailed examination of visual and somatosensory evoked activity using high-density electrical mapping in individuals with autism (N = 20) and precisely matched neurotypical controls (N = 20), recording large numbers ...


Stochastic Optimization Of Adaptive Enrichment Designs For Two Subpopulations, Aaron Fisher, Michael Rosenblum 2016 Harvard T.H. Chan School of Public Health

Stochastic Optimization Of Adaptive Enrichment Designs For Two Subpopulations, Aaron Fisher, Michael Rosenblum

Johns Hopkins University, Dept. of Biostatistics Working Papers

An adaptive enrichment design is a randomized trial that allows enrollment criteria to be modified at interim analyses, based on a preset decision rule. When there is prior uncertainty regarding treatment effect heterogeneity, these trial designs can provide improved power for detecting treatment effects in subpopulations. We present a simulated annealing approach to search over the space of decision rules and other parameters for an adaptive enrichment design. The goal is to minimize the expected number enrolled or expected duration, while preserving the appropriate power and Type I error rate. We also explore the benefits of parallel computation in the ...


Very Rapid Onset Cannabis Dependence Risk In Relation To Co-Occurring Use Of Other Psychoactive Drugs, Olga A. Vsevolozhskaya, Fernando A. Wagner, James C. Anthony 2016 University of Kentucky

Very Rapid Onset Cannabis Dependence Risk In Relation To Co-Occurring Use Of Other Psychoactive Drugs, Olga A. Vsevolozhskaya, Fernando A. Wagner, James C. Anthony

Biostatistics Presentations

Background: Epidemiological estimates for lifetime cumulative incidence indicate that for every 9-11 who start using cannabis, one becomes a case of the cannabis dependence syndrome (CDS) – i.e., roughly 9%-11%. More recent estimates clarify that CDS risk might be much lower among ’cannabis only’ users, due in part to the fact that many ’cannabis only’ users try the drug a few times and never again. We turned to Hill functional analysis in order to study CDS probability soon after 1st cannabis use, estimated across strata defined by the number of recent days of cannabis use, with an acknowledgment that ...


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