Statistical Models Commons^™

Minimum Description Length And Empirical Bayes Methods Of Identifying Snps Associated With Disease, Ye Yang, David R. Bickel

COBRA Preprint Series

The goal of determining which of hundreds of thousands of SNPs are associated with disease poses one of the most challenging multiple testing problems. Using the empirical Bayes approach, the local false discovery rate (LFDR) estimated using popular semiparametric models has enjoyed success in simultaneous inference. However, the estimated LFDR can be biased because the semiparametric approach tends to overestimate the proportion of the non-associated single nucleotide polymorphisms (SNPs). One of the negative consequences is that, like conventional p-values, such LFDR estimates cannot quantify the amount of information in the data that favors the null hypothesis of no disease-association.

We …

Stratifying Subjects For Treatment Selection With Censored Event Time Data From A Comparative Study, Lihui Zhao, Tianxi Cai, Lu Tian, Hajime Uno, Scott D. Solomon, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

Mixed Effect Poisson Log-Linear Models For Clinical And Epidemiological Sleep Hypnogram Data, Bruce J. Swihart, Brian S. Caffo Phd, Ciprian Crainiceanu Phd, Naresh M. Punjabi Phd, Md

Johns Hopkins University, Dept. of Biostatistics Working Papers

Bayesian Poisson log-linear multilevel models scalable to epidemiological studies are proposed to investigate population variability in sleep state transition rates. Hierarchical random effects are used to account for pairings of individuals and repeated measures within those individuals, as comparing diseased to non-diseased subjects while minimizing bias is of importance. Essentially, non-parametric piecewise constant hazards are estimated and smoothed, allowing for time-varying covariates and segment of the night comparisons. The Bayesian Poisson regression is justified through a re-derivation of a classical algebraic likelihood equivalence of Poisson regression with a log(time) offset and survival regression assuming exponentially distributed survival times. Such re-derivation …

Principled Sure Independence Screening For Cox Models With Ultra-High-Dimensional Covariates, Sihai Dave Zhao, Yi Li

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Unified Approach To Modeling Multivariate Binary Data Using Copulas Over Partitions, Bruce J. Swihart, Brian Caffo, Ciprian Crainiceanu

Johns Hopkins University, Dept. of Biostatistics Working Papers

Many seemingly disparate approaches for marginal modeling have been developed in recent years. We demonstrate that many current approaches for marginal modeling of correlated binary outcomes produce likelihoods that are equivalent to the proposed copula-based models herein. These general copula models of underlying latent threshold random variables yield likelihood based models for marginal fixed effects estimation and interpretation in the analysis of correlated binary data. Moreover, we propose a nomenclature and set of model relationships that substantially elucidates the complex area of marginalized models for binary data. A diverse collection of didactic mathematical and numerical examples are given to illustrate …

Nonparametric Regression With Missing Outcomes Using Weighted Kernel Estimating Equations, Lu Wang, Andrea Rotnitzky, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

Nonparametric And Semiparametric Analysis Of Current Status Data Subject To Outcome Misclassification, Victor G. Sal Y Rosas, James P. Hughes

UW Biostatistics Working Paper Series

In this article, we present nonparametric and semiparametric methods to analyze current status data subject to outcome misclassification. Our methods use nonparametric maximum likelihood estimation (NPMLE) to estimate the distribution function of the failure time when sensitivity and specificity may vary among subgroups. A nonparametric test is proposed for the two sample hypothesis testing. In regression analysis, we apply the Cox proportional hazard model and likelihood ratio based confidence intervals for the regression coefficients are proposed. Our methods are motivated and demonstrated by data collected from an infectious disease study in Seattle, WA.

An Analysis Of Nonignorable Nonresponse In A Survey With A Rotating Panel Design, Caterina Giusti, Roderick J. Little

The University of Michigan Department of Biostatistics Working Paper Series

Missing values to income questions are common in survey data. When the probabilities of nonresponse are assumed to depend on the observed information and not on the underlining unobserved amounts, the missing income values are missing at random (MAR), and methods such as sequential multiple imputation can be applied. However, the MAR assumption is often considered questionable in this context, since missingness of income is thought to be related to the value of income itself, after conditioning on available covariates. In this article we describe a sensitivity analysis based on a pattern-mixture model for deviations from MAR, in the context …

Robustness Of Approaches To Roc Curve Modeling Under Misspecification Of The Underlying Probability Model, Sean Devlin, Elizabeth Thomas, Scott S. Emerson

UW Biostatistics Working Paper Series

The receiver operating characteristic (ROC) curve is a tool of particular use in disease status classification with a continuous medical test (marker). A variety of statistical regression models have been proposed for the comparison of ROC curves for different markers across covariate groups. A full parametric modeling of the marker distribution has been generally found to be overly reliant on the strong parametric assumptions. Pepe (2003) has instead developed parametric models for the ROC curve that induce a semi-parametric model for the marker distributions. The estimating equations proposed for use in these ROC-GLM models may differ from commonly used estimating …

Causal Inference In Epidemiological Studies With Strong Confounding, Kelly L. Moore, Romain S. Neugebauer, Mark J. Van Der Laan, Ira B. Tager

U.C. Berkeley Division of Biostatistics Working Paper Series

One of the identifiabilty assumptions of causal effects defined by marginal structural model (MSM) parameters is the experimental treatment assignment (ETA) assumption. Practical violations of this assumption frequently occur in data analysis, when certain exposures are rarely observed within some strata of the population. The inverse probability of treatment weighted (IPTW) estimator is particularly sensitive to violations of this assumption, however, we demonstrate that this is a problem for all estimators of causal effects. This is due to the fact that the ETA assumption is about information (or lack thereof) in the data. A new class of causal models, causal …

Shrinkage Estimation Of Expression Fold Change As An Alternative To Testing Hypotheses Of Equivalent Expression, Zahra Montazeri, Corey M. Yanofsky, David R. Bickel

COBRA Preprint Series

Research on analyzing microarray data has focused on the problem of identifying differentially expressed genes to the neglect of the problem of how to integrate evidence that a gene is differentially expressed with information on the extent of its differential expression. Consequently, researchers currently prioritize genes for further study either on the basis of volcano plots or, more commonly, according to simple estimates of the fold change after filtering the genes with an arbitrary statistical significance threshold. While the subjective and informal nature of the former practice precludes quantification of its reliability, the latter practice is equivalent to using a …

A Spatio-Temporal Approach For Estimating Chronic Effects Of Air Pollution, Sonja Greven, Francesca Dominici, Scott L. Zeger

Johns Hopkins University, Dept. of Biostatistics Working Papers

Estimating the health risks associated with air pollution exposure is of great importance in public health. In air pollution epidemiology, two study designs have been used mainly. Time series studies estimate acute risk associated with short-term exposure. They compare day-to-day variation of pollution concentrations and mortality rates, and have been criticized for potential confounding by time-varying covariates. Cohort studies estimate chronic effects associated with long-term exposure. They compare long-term average pollution concentrations and time-to-death across cities, and have been criticized for potential confounding by individual risk factors or city-level characteristics.

We propose a new study design and a statistical model, …

A Class Of Semiparametric Mixture Cure Survival Models With Dependent Censoring, Megan Othus, Yi Li, Ram C. Tiwari

Harvard University Biostatistics Working Paper Series

No abstract provided.

Analysis Of Randomized Comparative Clinical Trial Data For Personalized Treatment Selections, Tianxi Cai, Lu Tian, Peggy H. Wong, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

Correlated Binary Regression Using Orthogonalized Residuals, Richard C. Zink, Bahjat F. Qaqish

COBRA Preprint Series

This paper focuses on marginal regression models for correlated binary responses when estimation of the association structure is of primary interest. A new estimating function approach based on orthogonalized residuals is proposed. This procedure allows a new representation and addresses some of the difficulties of the conditional-residual formulation of alternating logistic regressions of Carey, Zeger & Diggle (1993). The new method is illustrated with an analysis of data on impaired pulmonary function.

Group Comparison Of Eigenvalues And Eigenvectors Of Diffusion Tensors, Armin Schwartzman, Robert F. Dougherty, Jonathan E. Taylor

Harvard University Biostatistics Working Paper Series

No abstract provided.

Spatial Misalignment In Time Series Studies Of Air Pollution And Health Data, Roger D. Peng, Michelle L. Bell

Johns Hopkins University, Dept. of Biostatistics Working Papers

Time series studies of environmental exposures often involve comparing daily changes in a toxicant measured at a point in space with daily changes in an aggregate measure of health. Spatial misalignment of the exposure and response variables can bias the estimation of health risk and the magnitude of this bias depends on the spatial variation of the exposure of interest. In air pollution epidemiology, there is an increasing focus on estimating the health effects of the chemical components of particulate matter. One issue that is raised by this new focus is the spatial misalignment error introduced by the lack of …

Space-Time Regression Modeling Of Tree Growth Using The Skew-T Distribution, Farouk S. Nathoo

COBRA Preprint Series

In this article we present new statistical methodology for the analysis of repeated measures of spatially correlated growth data. Our motivating application, a ten year study of height growth in a plantation of even-aged white spruce, presents several challenges for statistical analysis. Here, the growth measurements arise from an asymmetric distribution, with heavy tails, and thus standard longitudinal regression models based on a Gaussian error structure are not appropriate. We seek more flexibility for modeling both skewness and fat tails, and achieve this within the class of skew-elliptical distributions. Within this framework, robust space-time regression models are formulated using random …

Predicting Intra-Urban Variation In Air Pollution Concentrations With Complex Spatio-Temporal Interactions, Adam A. Szpiro, Paul D. Sampson, Lianne Sheppard, Thomas Lumley, Sara D. Adar, Joel Kaufman

UW Biostatistics Working Paper Series

We describe a methodology for assigning individual estimates of long-term average air pollution concentrations that accounts for a complex spatio-temporal correlation structure and can accommodate unbalanced observations. This methodology has been developed as part of the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air), a prospective cohort study funded by the U.S. EPA to investigate the relationship between chronic exposure to air pollution and cardiovascular disease. Our hierarchical model decomposes the space-time field into a “mean” that includes dependence on covariates and spatially varying seasonal and long-term trends and a “residual” that accounts for spatially correlated deviations from the …

Optimal Cutpoint Estimation With Censored Data, Mithat Gonen, Camelia Sima

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

We consider the problem of selecting an optimal cutpoint for a continuous marker when the outcome of interest is subject to right censoring. Maximal chi square methods and receiver operating characteristic (ROC) curves-based methods are commonly-used when the outcome is binary. In this article we show that selecting the cutpoint that maximizes the concordance, a metric similar to the area under an ROC curve, is equivalent to maximizing the Youden index, a popular criterion when the ROC curve is used to choose a threshold. We use this as a basis for proposing maximal concordance as a metric to use with …

A Simple Index Of Smoking, Abhaya Indrayan Dr., Rajeev Kumar Mr., Shridhar Dwivedi Dr.

COBRA Preprint Series

Background: Cigarette smoking is implicated in a large number of diseases and other adverse health conditions. Among the dimensions of smoking are number of cigarettes smoked per day, duration of smoking, passive smoking, smoking of filter cigarettes, age at start, and duration elapsed since quitting by ex-smokers. The practice so far is to study most of these separately. We develop a simple index that integrates these dimensions of smoking into a single metric, and suggest that this index be developed further. Method: The index is developed under a series of natural assumptions. Broadly, these are (i) the burden of smoking …

The Strength Of Statistical Evidence For Composite Hypotheses With An Application To Multiple Comparisons, David R. Bickel

COBRA Preprint Series

The strength of the statistical evidence in a sample of data that favors one composite hypothesis over another may be quantified by the likelihood ratio using the parameter value consistent with each hypothesis that maximizes the likelihood function. Unlike the p-value and the Bayes factor, this measure of evidence is coherent in the sense that it cannot support a hypothesis over any hypothesis that it entails. Further, when comparing the hypothesis that the parameter lies outside a non-trivial interval to the hypotheses that it lies within the interval, the proposed measure of evidence almost always asymptotically favors the correct hypothesis …

Calibrating Parametric Subject-Specific Risk Estimation, Tianxi Cai, Lu Tian, Hajime Uno, Scott D. Solomon, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

Multilevel Latent Class Models With Dirichlet Mixing Distribution, Chongzhi Di, Karen Bandeen-Roche

Johns Hopkins University, Dept. of Biostatistics Working Papers

Latent class analysis (LCA) and latent class regression (LCR) are widely used for modeling multivariate categorical outcomes in social sciences and biomedical studies. Standard analyses assume data of different respondents to be mutually independent, excluding application of the methods to familial and other designs in which participants are clustered. In this paper, we develop multilevel latent class model, in which subpopulation mixing probabilities are treated as random effects that vary among clusters according to a common Dirichlet distribution. We apply the Expectation-Maximization (EM) algorithm for model fitting by maximum likelihood (ML). This approach works well, but is computationally intensive when …

Evaluating Subject-Level Incremental Values Of New Markers For Risk Classification Rule, Tianxi Cai, Lu Tian, Donald M. Lloyd-Jones, L. J. Wei

Harvard University Biostatistics Working Paper Series

No abstract provided.

Limitations Of Remotely-Sensed Aerosol As A Spatial Proxy For Fine Particulate Matter, Christopher J. Paciorek, Yang Liu

Harvard University Biostatistics Working Paper Series

Recent research highlights the promise of remotely-sensed aerosol optical depth (AOD) as a proxy for ground-level PM2.5. Particular interest lies in the information on spatial heterogeneity potentially provided by AOD, with important application to estimating and monitoring pollution exposure for public health purposes. Given the temporal and spatio-temporal correlations reported between AOD and PM2.5 , it is tempting to interpret the spatial patterns in AOD as reflecting patterns in PM2.5 . Here we find only limited spatial associations of AOD from three satellite retrievals with PM2.5 over the eastern U.S. at the daily and yearly levels in 2004. We then …

Expanded Technical Report: Mapping Ancient Forests: Bayesian Inference For Spatio-Temporal Trends In Forest Composition Using The Fossil Pollen Proxy Record, Christopher J. Paciorek, Jason S. Mclachlan

Harvard University Biostatistics Working Paper Series

No abstract provided.

Measurement Error Caused By Spatial Misalignment In Environmental Epidemiology, Alexandros Gryparis, Christopher J. Paciorek, Ariana Zeka, Joel Schwartz, Brent A. Coull

Harvard University Biostatistics Working Paper Series

No abstract provided.

Practical Large-Scale Spatio-Temporal Modeling Of Particulate Matter Concentrations, Christopher J. Paciorek, Jeff D. Yanosky, Robin C. Puett, Francine Laden, Helen H. Suh

Harvard University Biostatistics Working Paper Series

The last two decades have seen intense scientific and regulatory interest in the health effects of particulate matter (PM). Influential epidemiological studies that characterize chronic exposure of individuals rely on monitoring data that are sparse in space and time, so they often assign the same exposure to participants in large geographic areas and across time. We estimate monthly PM during 1988-2002 in a large spatial domain for use in studying health effects in the Nurses' Health Study. We develop a conceptually simple spatio-temporal model that uses a rich set of covariates. The model is used to estimate concentrations of PM10 …

Confidence Intervals For Negative Binomial Random Variables Of High Dispersion, David Shilane, Alan E. Hubbard, S N. Evans

U.C. Berkeley Division of Biostatistics Working Paper Series

This paper considers the problem of constructing confidence intervals for the mean of a Negative Binomial random variable based upon sampled data. When the sample size is large, we traditionally rely upon a Normal distribution approximation to construct these intervals. However, we demonstrate that the sample mean of highly dispersed Negative Binomials exhibits a slow convergence to the Normal in distribution as a function of the sample size. As a result, standard techniques (such as the Normal approximation and bootstrap) that construct confidence intervals for the mean will typically be too narrow and significantly undercover in the case of high …