Statistics and Probability Commons^™

Semiparametric Maximum Likelihood Estimation In Normal Transformation Models For Bivariate Survival Data, Yi Li, Ross L. Prentice, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

Doubly Robust Ecological Inference, Daniel B. Rubin, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

The ecological inference problem is a famous longstanding puzzle that arises in many disciplines. The usual formulation in epidemiology is that we would like to quantify an exposure-disease association by obtaining disease rates among the exposed and unexposed, but only have access to exposure rates and disease rates for several regions. The problem is generally intractable, but can be attacked under the assumptions of King's (1997) extended technique if we can correctly specify a model for a certain conditional distribution. We introduce a procedure that it is a valid approach if either this original model is correct or if we …

Targeted Methods For Biomarker Discovery, The Search For A Standard, Catherine Tuglus, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

More often than not biomarker studies analyze large quantities of variables with complicated and generally unknown correlation structure. There are numerous statistical methods which attempt to unravel these variables and determine the underlying mechanism through identification of causally related biomarkers. Results from these methods are generally difficult to interpret and nearly impossible to compare across studies. The FDA has currently called for a standardization of methods and protocol for biomarker detection. In response, we propose targeted variable importance (tVIM) as a standardized method for biomarker discovery. Through the use of targeted Maximum Likelihood, tVIM provides double robust estimates of variable …

Marginal Structural Models For Partial Exposure Regimes, Stijn Vansteelandt, Karl Mertens, Carl Suetens, Els Goetghebeur

Harvard University Biostatistics Working Paper Series

Intensive care unit (ICU) patients are ell known to be highly susceptible for nosocomial (i.e. hospital-acquired) infections due to their poor health and many invasive therapeutic treatments. The effects of acquiring such infections in ICU on mortality are however ill understood. Our goal is to quantify these effects using data from the National Surveillance Study of Nosocomial Infections in Intensive Care

Units (Belgium). This is a challenging problem because of the presence of time-dependent confounders (such as exposure to mechanical ventilation)which lie on the causal path from infection to mortality. Standard statistical analyses may be severely misleading in such settings …

Estimation Of Controlled Direct Effects, Sylvie Goetgeluk, Stijn Vansteelandt, Els Goetghebeur

Harvard University Biostatistics Working Paper Series

No abstract provided.

Correcting Instrumental Variables Estimators For Systematic Measurement Error, Stijn Vansteelandt, Manoochehr Babanezhad, Els Goetghebeur

Harvard University Biostatistics Working Paper Series

No abstract provided.

Empirical Efficiency Maximization, Daniel B. Rubin, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

It has long been recognized that covariate adjustment can increase precision, even when it is not strictly necessary. The phenomenon is particularly emphasized in clinical trials, whether using continuous, categorical, or censored time-to-event outcomes. Adjustment is often straightforward when a discrete covariate partitions the sample into a handful of strata, but becomes more involved when modern studies collect copious amounts of baseline information on each subject.

The dilemma helped motivate locally efficient estimation for coarsened data structures, as surveyed in the books of van der Laan and Robins (2003) and Tsiatis (2006). Here one fits a relatively small working model …

Power Boosting In Genome-Wide Studies Via Methods For Multivariate Outcomes, Mary J. Emond

UW Biostatistics Working Paper Series

Whole-genome studies are becoming a mainstay of biomedical research. Examples include expression array experiments, comparative genomic hybridization analyses and large case-control studies for detecting polymorphism/disease associations. The tactic of applying a regression model to every locus to obtain test statistics is useful in such studies. However, this approach ignores potential correlation structure in the data that could be used to gain power, particularly when a Bonferroni correction is applied to adjust for multiple testing. In this article, we propose using regression techniques for misspecified multivariate outcomes to increase statistical power over independence-based modeling at each locus. Even when the outcome …

A Likelihood Based Method For Real Time Estimation Of The Serial Interval And Reproductive Number Of An Epidemic, Laura Forsberg White, Marcello Pagano

Harvard University Biostatistics Working Paper Series

No abstract provided.

Spatio-Temporal Analysis Of Areal Data And Discovery Of Neighborhood Relationships In Conditionally Autoregressive Models, Subharup Guha, Louise Ryan

Harvard University Biostatistics Working Paper Series

No abstract provided.

Semiparametric Regression Of Multi-Dimensional Genetic Pathway Data: Least Squares Kernel Machines And Linear Mixed Models, Dawei Liu, Xihong Lin, Debashis Ghosh

Harvard University Biostatistics Working Paper Series

No abstract provided.

Statistical Analysis Of Air Pollution Panel Studies: An Illustration, Holly Janes, Lianne Sheppard, Kristen Shepherd

UW Biostatistics Working Paper Series

The panel study design is commonly used to evaluate the short-term health effects of air pollution. Standard statistical methods for analyzing longitudinal data are available, but the literature reveals that the techniques are not well understood by practitioners. We illustrate these methods using data from the 1999 to 2002 Seattle panel study. Marginal, conditional, and transitional approaches for modeling longitudinal data are reviewed and contrasted with respect to their parameter interpretation and methods for accounting for correlation and dealing with missing data. We also discuss and illustrate techniques for controlling for time-dependent and time-independent confounding, and for exploring and summarizing …

Spatial Cluster Detection For Censored Outcome Data, Andrea J. Cook, Diane Gold, Yi Li

Harvard University Biostatistics Working Paper Series

No abstract provided.

Extending Marginal Structural Models Through Local, Penalized, And Additive Learning, Daniel Rubin, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Marginal structural models (MSMs) allow one to form causal inferences from data, by specifying a relationship between a treatment and the marginal distribution of a corresponding counterfactual outcome. Following their introduction in Robins (1997), MSMs have typically been fit after assuming a semiparametric model, and then estimating a finite dimensional parameter. van der Laan and Dudoit (2003) proposed to instead view MSM fitting not as a task of semiparametric parameter estimation, but of nonparametric function approximation. They introduced a class of causal effect estimators based on mapping loss functions suitable for the unavailable counterfactual data to those suitable for the …

Structural Inference In Transition Measurement Error Models For Longitudinal Data, Wenqin Pan, Xihong Lin, Donglin Zeng

Harvard University Biostatistics Working Paper Series

No abstract provided.

Estimation In Semiparametric Transition Measurement Error Models For Longitudinal Data, Wenqin Pan, Donglin Zeng, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

Nonparametric Regression Using Local Kernel Estimating Equations For Correlated Failure Time Data, Zhangsheng Yu, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

Causal Inference In Hybrid Intervention Trials Involving Treatment Choice, Qi Long, Rod Little, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Comparison Of Methods For Estimating The Causal Effect Of A Treatment In Randomized Clinical Trials Subject To Noncompliance, Rod Little, Qi Long, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

Relative Risk Regression In Medical Research: Models, Contrasts, Estimators, And Algorithms, Thomas Lumley, Richard Kronmal, Shuangge Ma

UW Biostatistics Working Paper Series

The relative risk or prevalence ratio is a natural and familiar summary of association between a binary outcome and an exposure or intervention. For rare events, the relative risk can be approximately estimated by logistic regression. For common events estimation is more difficult. We review proposed estimation algorithms for relative risk regression. Some of these give inconsistent estimates or invalid standard errors. We show that the methods that give correct inference can be viewed as arising from a family of quasilikelihood estimating functions for the same generalized linear model, differing in their efficiency and in their robustness to outlying values …

Causal Comparisons In Randomized Trials Of Two Active Treatments: The Effect Of Supervised Exercise To Promote Smoking Cessation, Jason Roy, Joseph W. Hogan

COBRA Preprint Series

In behavioral medicine trials, such as smoking cessation trials, two or more active treatments are often compared. Noncompliance by some subjects with their assigned treatment poses a challenge to the data analyst. Causal parameters of interest might include those defined by subpopulations based on their potential compliance status under each assignment, using the principal stratification framework (e.g., causal effect of new therapy compared to standard therapy among subjects that would comply with either intervention). Even if subjects in one arm do not have access to the other treatment(s), the causal effect of each treatment typically can only be identified from …

Low Birth Weight, Very Low Birth Weight And Infant Mortality In San Bernardino County : A Secondary Analysis Of Maternal Factors, Rebecca D. Nanyonjo

Loma Linda University Electronic Theses, Dissertations & Projects

Purpose: National and state infant mortality rates have slowly declined over the last several years. Despite this reduction, San Bernardino County still has one of the highest infant mortality rates in California and racial disparities between Black and White infants not only persist but continue to widen. These disparities remain at the forefront of concern. Healthy People 2010 target objectives have yet to be reached, while national and state proposed plans have supported the statement that a community's largest health problem is initiated by its infant mortality. The purpose of this study was to investigate maternal factors through use of …

Semiparametric Latent Variable Regression Models For Spatio-Temporal Modeling Of Mobile Source Particles In The Greater Boston Area, Alexandros Gryparis, Brent A. Coull, Joel Schwartz, Helen H. Suh

Harvard University Biostatistics Working Paper Series

Traffic particle concentrations show considerable spatial variability within a metropolitan area. We consider latent variable semiparametric regression models for modeling the spatial and temporal variability of black carbon and elemental carbon concentrations in the greater Boston area. Measurements of these pollutants, which are markers of traffic particles, were obtained from several individual exposure studies conducted at specific household locations as well as 15 ambient monitoring sites in the city. The models allow for both flexible, nonlinear effects of covariates and for unexplained spatial and temporal variability in exposure. In addition, the different individual exposure studies recorded different surrogates of traffic …

Different Public Health Interventions Have Varying Effects, Paula Diehr, Anne B. Newman, Liming Cai, Ann Derleth

UW Biostatistics Working Paper Series

Objective: To compare performance of one-time health interventions to those that change the probability of transitioning from one health state to another. Study Design and Setting: We used multi-state life table methods to estimate the impact of eight types of interventions on several outcomes. Results: In a cohort beginning at age 65, curing all the sick persons at baseline would increase life expectancy by 0.23 years and increase years of healthy life by .54 years. An equal amount of improvement could be obtained with a 12% decrease in the probability of getting sick, a 16% increase in the probability of …

Gpnn: Power Studies And Applications Of A Neural Network Method For Detecting Gene-Gene Interactions In Studies Of Human Disease, Alison A. Motsinger, Stephen L. Lee, George Mellick, Marylyn D. Ritchie

Dartmouth Scholarship

The identification and characterization of genes that influence the risk of common, complex multifactorial disease primarily through interactions with other genes and environmental factors remains a statistical and computational challenge in genetic epidemiology. We have previously introduced a genetic programming optimized neural network (GPNN) as a method for optimizing the architecture of a neural network to improve the identification of gene combinations associated with disease risk. The goal of this study was to evaluate the power of GPNN for identifying high-order gene-gene interactions. We were also interested in applying GPNN to a real data analysis in Parkinson's disease.

Cyclosporin Versus Tacrolimus For Liver Transplanted Patients, Elizabeth Haddad, Vivian Mcalister, Elizabeth Renouf, Richard Malthaner, Mette S. Kjaer, Lise Lotte Gluud

Surgery Publications

A systematic review of randomized clinical trials (RCT) was undertaken to evaluate the beneficial and harmful effects of immunosuppression with cyclosporin versus tacrolimus for liver transplanted patients. MEDLINE, EMBASE, Cochrane Central and Hepato-Biliary Group Controlled Trials Registers were searched. Using fixed and random effects model, relative risk (RR), values <1 favoring>tacrolimus, with 95% confidence intervals (CI) were calculated. Of 717 potentially relevant references, 16 RCTs were eligible for inclusion. Mortality and graft loss at 1 year were significantly reduced in tacrolimus-treated recipients (Death: RR 0.85, 95% CI 0.73-0.99; graft loss: RR 0.73, 95% CI 0.61-0.86). Tacrolimus reduced the number of recipients …

Population Intervention Models In Causal Inference, Alan E. Hubbard, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Marginal structural models (MSM) provide a powerful tool for estimating the causal effect of a] treatment variable or risk variable on the distribution of a disease in a population. These models, as originally introduced by Robins (e.g., Robins (2000a), Robins (2000b), van der Laan and Robins (2002)), model the marginal distributions of treatment-specific counterfactual outcomes, possibly conditional on a subset of the baseline covariates, and its dependence on treatment. Marginal structural models are particularly useful in the context of longitudinal data structures, in which each subject's treatment and covariate history are measured over time, and an outcome is recorded at …

Gauss-Seidel Estimation Of Generalized Linear Mixed Models With Application To Poisson Modeling Of Spatially Varying Disease Rates, Subharup Guha, Louise Ryan

Harvard University Biostatistics Working Paper Series

Generalized linear mixed models (GLMMs) provide an elegant framework for the analysis of correlated data. Due to the non-closed form of the likelihood, GLMMs are often fit by computational procedures like penalized quasi-likelihood (PQL). Special cases of these models are generalized linear models (GLMs), which are often fit using algorithms like iterative weighted least squares (IWLS). High computational costs and memory space constraints often make it difficult to apply these iterative procedures to data sets with very large number of cases.

This paper proposes a computationally efficient strategy based on the Gauss-Seidel algorithm that iteratively fits sub-models of the GLMM …

Computational Techniques For Spatial Logistic Regression With Large Datasets, Christopher J. Paciorek, Louise Ryan

Harvard University Biostatistics Working Paper Series

In epidemiological work, outcomes are frequently non-normal, sample sizes may be large, and effects are often small. To relate health outcomes to geographic risk factors, fast and powerful methods for fitting spatial models, particularly for non-normal data, are required. We focus on binary outcomes, with the risk surface a smooth function of space. We compare penalized likelihood models, including the penalized quasi-likelihood (PQL) approach, and Bayesian models based on fit, speed, and ease of implementation.

A Bayesian model using a spectral basis representation of the spatial surface provides the best tradeoff of sensitivity and specificity in simulations, detecting real spatial …

A Nonstationary Negative Binomial Time Series With Time-Dependent Covariates: Enterococcus Counts In Boston Harbor, E. Andres Houseman, Brent Coull, James P. Shine

Harvard University Biostatistics Working Paper Series

Boston Harbor has had a history of poor water quality, including contamination by enteric pathogens. We conduct a statistical analysis of data collected by the Massachusetts Water Resources Authority (MWRA) between 1996 and 2002 to evaluate the effects of court-mandated improvements in sewage treatment. Motivated by the ineffectiveness of standard Poisson mixture models and their zero-inflated counterparts, we propose a new negative binomial model for time series of Enterococcus counts in Boston Harbor, where nonstationarity and autocorrelation are modeled using a nonparametric smooth function of time in the predictor. Without further restrictions, this function is not identifiable in the presence …