Statistical Models Commons^™

Does The Effect Of Micronutrient Supplementation On Neonatal Survival Vary With Respect To The Percentiles Of The Birth Weight Distribution?, Francesca Dominici, Scott L. Zeger, Giovanni Parmigiani, Joanne Katz, Parul Christian

Johns Hopkins University, Dept. of Biostatistics Working Papers

Scientific Background: In developing countries, higher infant mortality is partially caused by poor maternal and fetal nutrition. Clinical trials of micronutrient supplementation are aimed at reducing the risk of infant mortality by increasing birth weight. Because infant mortality is greatest among the low birth weight infants (LBW) (less than or equal to 2500 grams), an effective intervention might be needed to increase birth weight among the smallest babies. Although it has been demonstrated that supplementation increases the birth weight in a trial conducted in Nepal, there is inconclusive evidence that the supplementation improves their survival. It has been hypothesized that …

Linear Regression Of Censored Length-Biased Lifetimes, Ying Qing Chen, Yan Wang

UW Biostatistics Working Paper Series

Length-biased lifetimes may be collected in observational studies or sample surveys due to biased sampling scheme. In this article, we use a linear regression model, namely, the accelerated failure time model, for the population lifetime distributions in regression analysis of the length-biased lifetimes. It is discovered that the associated regression parameters are invariant under the length-biased sampling scheme. According to this discovery, we propose the quasi partial score estimating equations to estimate the population regression parameters. The proposed methodologies are evaluated and demonstrated by simulation studies and an application to actual data set.

Cross-Validated Bagged Learning, Mark J. Van Der Laan, Sandra E. Sinisi, Maya L. Petersen

U.C. Berkeley Division of Biostatistics Working Paper Series

Many applications aim to learn a high dimensional parameter of a data generating distribution based on a sample of independent and identically distributed observations. For example, the goal might be to estimate the conditional mean of an outcome given a list of input variables. In this prediction context, Breiman (1996a) introduced bootstrap aggregating (bagging) as a method to reduce the variance of a given estimator at little cost to bias. Bagging involves applying the estimator to multiple bootstrap samples, and averaging the result across bootstrap samples. In order to deal with the curse of dimensionality, typical practice has been to …

Spatio-Temporal Point Processes: Methods And Applications, Peter J. Diggle

Johns Hopkins University, Dept. of Biostatistics Working Papers

No abstract provided.

Model Choice In Time Series Studies Of Air Pollution And Mortality, Roger D. Peng, Francesca Dominici, Thomas A. Louis

Johns Hopkins University, Dept. of Biostatistics Working Papers

Multi-city time series studies of particulate matter (PM) and mortality and morbidity have provided evidence that daily variation in air pollution levels is associated with daily variation in mortality counts. These findings served as key epidemiological evidence for the recent review of the United States National Ambient Air Quality Standards (NAAQS) for PM. As a result, methodological issues concerning time series analysis of the relation between air pollution and health have attracted the attention of the scientific community and critics have raised concerns about the adequacy of current model formulations. Time series data on pollution and mortality are generally analyzed …

New Statistical Paradigms Leading To Web-Based Tools For Clinical/Translational Science, Knut M. Wittkowski

COBRA Preprint Series

As the field of functional genetics and genomics is beginning to mature, we become confronted with new challenges. The constant drop in price for sequencing and gene expression profiling as well as the increasing number of genetic and genomic variables that can be measured makes it feasible to address more complex questions. The success with rare diseases caused by single loci or genes has provided us with a proof-of-concept that new therapies can be developed based on functional genomics and genetics.

Common diseases, however, typically involve genetic epistasis, genomic pathways, and proteomic pattern. Moreover, to better understand the underlying biologi-cal …

Causal Inference In Longitudinal Studies With History-Restricted Marginal Structural Models, Romain Neugebauer, Mark J. Van Der Laan, Ira B. Tager

U.C. Berkeley Division of Biostatistics Working Paper Series

Causal Inference based on Marginal Structural Models (MSMs) is particularly attractive to subject-matter investigators because MSM parameters provide explicit representations of causal effects. We introduce History-Restricted Marginal Structural Models (HRMSMs) for longitudinal data for the purpose of defining causal parameters which may often be better suited for Public Health research. This new class of MSMs allows investigators to analyze the causal effect of a treatment on an outcome based on a fixed, shorter and user-specified history of exposure compared to MSMs. By default, the latter represents the treatment causal effect of interest based on a treatment history defined by the …

The Sensitivity And Specificity Of Markers For Event Times, Tianxi Cai, Margaret S. Pepe, Thomas Lumley, Yingye Zheng, Nancy Swords Jenny

Harvard University Biostatistics Working Paper Series

No abstract provided.

Survival Ensembles, Torsten Hothorn, Peter Buhlmann, Sandrine Dudoit, Annette M. Molinaro, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

We propose a unified and flexible framework for ensemble learning in the presence of censoring. For right-censored data, we introduce a random forest algorithm and a generic gradient boosting algorithm for the construction of prognostic models. The methodology is utilized for predicting the survival time of patients suffering from acute myeloid leukemia based on clinical and genetic covariates. Furthermore, we compare the diagnostic capabilities of the proposed censored data random forest and boosting methods applied to the recurrence free survival time of node positive breast cancer patients with previously published findings.

Combining Predictors For Classification Using The Area Under The Roc Curve, Margaret S. Pepe, Tianxi Cai, Zheng Zhang, Gary M. Longton

UW Biostatistics Working Paper Series

No single biomarker for cancer is considered adequately sensitive and specific for cancer screening. It is expected that the results of multiple markers will need to be combined in order to yield adequately accurate classification. Typically the objective function that is optimized for combining markers is the likelihood function. In this paper we consider an alternative objective function -- the area under the empirical receiver operating characteristic curve (AUC). We note that it yields consistent estimates of parameters in a generalized linear model for the risk score but does not require specifying the link function. Like logistic regression it yields …

Robust Inferences For Covariate Effects On Survival Time With Censored Linear Regression Models, Larry Leon, Tianxi Cai, L. J. Wei

Harvard University Biostatistics Working Paper Series

Various inference procedures for linear regression models with censored failure times have been studied extensively. Recent developments on efficient algorithms to implement these procedures enhance the practical usage of such models in survival analysis. In this article, we present robust inferences for certain covariate effects on the failure time in the presence of "nuisance" confounders under a semiparametric, partial linear regression setting. Specifically, the estimation procedures for the regression coefficients of interest are derived from a working linear model and are valid even when the function of the confounders in the model is not correctly specified. The new proposals are …

A Hybrid Newton-Type Method For The Linear Regression In Case-Cohort Studies, Menggang Yu, Bin Nan

The University of Michigan Department of Biostatistics Working Paper Series

Case-cohort designs are increasingly commonly used in large epidemiological cohort studies. Nan, Yu, and Kalbeisch (2004) provided the asymptotic results for censored linear regression models in case-cohort studies. In this article, we consider computational aspects of their proposed rank based estimating methods. We show that the rank based discontinuous estimating functions for case-cohort studies are monotone, a property established for cohort data in the literature, when generalized Gehan type of weights are used. Though the estimating problem can be formulated to a linear programming problem as that for cohort data, due to its easily uncontrollable large scale even for a …

Ranking Usrds Provider-Specific Smrs From 1998-2001, Rongheng Lin, Thomas A. Louis, Susan M. Paddock, Greg Ridgeway

Johns Hopkins University, Dept. of Biostatistics Working Papers

Provider profiling (ranking, "league tables") is prevalent in health services research. Similarly, comparing educational institutions and identifying differentially expressed genes depend on ranking. Effective ranking procedures must be structured by a hierarchical (Bayesian) model and guided by a ranking-specific loss function, however even optimal methods can perform poorly and estimates must be accompanied by uncertainty assessments. We use the 1998-2001 Standardized Mortality Ratio (SMR) data from United States Renal Data System (USRDS) as a platform to identify issues and approaches. Our analyses extend Liu et al. (2004) by combining evidence over multiple years via an AR(1) model; by considering estimates …

Semiparametric Regression In Capture-Recapture Modelling, O. Gimenez, C. Barbraud, Ciprian M. Crainiceanu, S. Jenouvrier, B.T. Morgan

Johns Hopkins University, Dept. of Biostatistics Working Papers

Capture-recapture models were developed to estimate survival using data arising from marking and monitoring wild animals over time. Variation in the survival process may be explained by incorporating relevant covariates. We develop nonparametric and semiparametric regression models for estimating survival in capture-recapture models. A fully Bayesian approach using MCMC simulations was employed to estimate the model parameters. The work is illustrated by a study of Snow petrels, in which survival probabilities are expressed as nonlinear functions of a climate covariate, using data from a 40-year study on marked individuals, nesting at Petrels Island, Terre Adelie.

Semi-Parametric Single-Index Two-Part Regression Models, Xiao-Hua Zhou, Hua Liang

UW Biostatistics Working Paper Series

In this paper, we proposed a semi-parametric single-index two-part regression model to weaken assumptions in parametric regression methods that were frequently used in the analysis of skewed data with additional zero values. The estimation procedure for the parameters of interest in the model was easily implemented. The proposed estimators were shown to be consistent and asymptotically normal. Through a simulation study, we showed that the proposed estimators have reasonable finite-sample performance. We illustrated the application of the proposed method in one real study on the analysis of health care costs.

The Proportional Odds Model For Assessing Rater Agreement With Multiple Modalities, Elizabeth Garrett-Mayer, Steven N. Goodman, Ralph H. Hruban

Johns Hopkins University, Dept. of Biostatistics Working Papers

In this paper, we develop a model for evaluating an ordinal rating systems where we assume that the true underlying disease state is continuous in nature. Our approach in motivated by a dataset with 35 microscopic slides with 35 representative duct lesions of the pancreas. Each of the slides was evaluated by eight raters using two novel rating systems (PanIN illustrations and PanIN nomenclature),where each rater used each systems to rate the slide with slide identity masked between evaluations. We find that the two methods perform equally well but that differentiation of higher grade lesions is more consistent across raters …

A Bayesian Mixture Model Relating Dose To Critical Organs And Functional Complication In 3d Conformal Radiation Therapy, Tim Johnson, Jeremy Taylor, Randall K. Ten Haken, Avraham Eisbruch

The University of Michigan Department of Biostatistics Working Paper Series

A goal of radiation therapy is to deliver maximum dose to the target tumor while minimizing complications due to irradiation of critical organs. Technological advances in 3D conformal radiation therapy has allowed great strides in realizing this goal, however complications may still arise. Critical organs may be adjacent to tumors or in the path of the radiation beam. Several mathematical models have been proposed that describe a relationship between dose and observed functional complication, however only a few published studies have successfully fit these models to data using modern statistical methods which make efficient use of the data. One complication …

On Marginalized Multilevel Models And Their Computation, Michael E. Griswold, Scott L. Zeger

Johns Hopkins University, Dept. of Biostatistics Working Papers

Clustered data analysis is characterized by the need to describe both systematic variation in a mean model and cluster-dependent random variation in an association model. Marginalized multilevel models embrace the robustness and interpretations of a marginal mean model, while retaining the likelihood inference capabilities and flexible dependence structures of a conditional association model. Although there has been increasing recognition of the attractiveness of marginalized multilevel models, there has been a gap in their practical application arising from a lack of readily available estimation procedures. We extend the marginalized multilevel model to allow for nonlinear functions in both the mean and …

Semiparametric Binary Regression Under Monotonicity Constraints, Moulinath Banerjee, Pinaki Biswas, Debashis Ghosh

The University of Michigan Department of Biostatistics Working Paper Series

Summary: We study a binary regression model where the response variable $\Delta$ is the indicator of an event of interest (for example, the incidence of cancer) and the set of covariates can be partitioned as $(X,Z)$ where $Z$ (real valued) is the covariate of primary interest and $X$ (vector valued) denotes a set of control variables. For any fixed $X$, the conditional probability of the event of interest is assumed to be a monotonic function of $Z$. The effect of the control variables is captured by a regression parameter $\beta$. We show that the baseline conditional probability function (corresponding to …

A Bayesian Method For Finding Interactions In Genomic Studies, Wei Chen, Debashis Ghosh, Trivellore E. Raghuanthan, Sharon Kardia

The University of Michigan Department of Biostatistics Working Paper Series

An important step in building a multiple regression model is the selection of predictors. In genomic and epidemiologic studies, datasets with a small sample size and a large number of predictors are common. In such settings, most standard methods for identifying a good subset of predictors are unstable. Furthermore, there is an increasing emphasis towards identification of interactions, which has not been studied much in the statistical literature. We propose a method, called BSI (Bayesian Selection of Interactions), for selecting predictors in a regression setting when the number of predictors is considerably larger than the sample size with a focus …

Spatially Adaptive Bayesian P-Splines With Heteroscedastic Errors, Ciprian M. Crainiceanu, David Ruppert, Raymond J. Carroll

Johns Hopkins University, Dept. of Biostatistics Working Papers

An increasingly popular tool for nonparametric smoothing are penalized splines (P-splines) which use low-rank spline bases to make computations tractable while maintaining accuracy as good as smoothing splines. This paper extends penalized spline methodology by both modeling the variance function nonparametrically and using a spatially adaptive smoothing parameter. These extensions have been studied before, but never together and never in the multivariate case. This combination is needed for satisfactory inference and can be implemented effectively by Bayesian \mbox{MCMC}. The variance process controlling the spatially-adaptive shrinkage of the mean and the variance of the heteroscedastic error process are modeled as log-penalized …

Bayesian Hierarchical Distributed Lag Models For Summer Ozone Exposure And Cardio-Respiratory Mortality, Yi Huang, Francesca Dominici, Michelle L. Bell

Johns Hopkins University, Dept. of Biostatistics Working Papers

In this paper, we develop Bayesian hierarchical distributed lag models for estimating associations between daily variations in summer ozone levels and daily variations in cardiovascular and respiratory (CVDRESP) mortality counts for 19 U.S. large cities included in the National Morbidity Mortality Air Pollution Study (NMMAPS) for the period 1987 - 1994.

At the first stage, we define a semi-parametric distributed lag Poisson regression model to estimate city-specific relative rates of CVDRESP associated with short-term exposure to summer ozone. At the second stage, we specify a class of distributions for the true city-specific relative rates to estimate an overall effect by …

Gllamm Manual, Sophia Rabe-Hesketh, Anders Skrondal, Andrew Pickles

U.C. Berkeley Division of Biostatistics Working Paper Series

This manual describes a Stata program gllamm that can estimate Generalized Linear Latent and Mixed Models (GLLAMMs). GLLAMMs are a class of multilevel latent variable models for (multivariate) responses of mixed type including continuous responses, counts, duration/survival data, dichotomous, ordered and unordered categorical responses and rankings. The latent variables (common factors or random effects) can be assumed to be discrete or to have a multivariate normal distribution. Examples of models in this class are multilevel generalized linear models or generalized linear mixed models, multilevel factor or latent trait models, item response models, latent class models and multilevel structural equation models. …

Data Adaptive Estimation Of The Treatment Specific Mean, Yue Wang, Oliver Bembom, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

An important problem in epidemiology and medical research is the estimation of the causal effect of a treatment action at a single point in time on the mean of an outcome, possibly within strata of the target population defined by a subset of the baseline covariates. Current approaches to this problem are based on marginal structural models, i.e., parametric models for the marginal distribution of counterfactural outcomes as a function of treatment and effect modifiers. The various estimators developed in this context furthermore each depend on a high-dimensional nuisance parameter whose estimation currently also relies on parametric models. Since misspecification …

Finding Cancer Subtypes In Microarray Data Using Random Projections, Debashis Ghosh

The University of Michigan Department of Biostatistics Working Paper Series

One of the benefits of profiling of cancer samples using microarrays is the generation of molecular fingerprints that will define subtypes of disease. Such subgroups have typically been found in microarray data using hierarchical clustering. A major problem in interpretation of the output is determining the number of clusters. We approach the problem of determining disease subtypes using mixture models. A novel estimation procedure of the parameters in the mixture model is developed based on a combination of random projections and the expectation-maximization algorithm. Because the approach is probabilistic, our approach provides a measure for the number of true clusters …

Semiparametric Methods For The Binormal Model With Multiple Biomarkers, Debashis Ghosh

The University of Michigan Department of Biostatistics Working Paper Series

Abstract: In diagnostic medicine, there is great interest in developing strategies for combining biomarkers in order to optimize classification accuracy. A popular model that has been used when one biomarker is available is the binormal model. Extension of the model to accommodate multiple biomarkers has not been considered in this literature. Here, we consider a multivariate binormal framework for combining biomarkers using copula functions that leads to a natural multivariate extension of the binormal model. Estimation in this model will be done using rank-based procedures. We also discuss adjustment for covariates in this class of models and provide a simple …

Cholesky Residuals For Assessing Normal Errors In A Linear Model With Correlated Outcomes: Technical Report, E. Andres Houseman, Louise Ryan, Brent Coull

Harvard University Biostatistics Working Paper Series

Despite the widespread popularity of linear models for correlated outcomes (e.g. linear mixed models and time series models), distribution diagnostic methodology remains relatively underdeveloped in this context. In this paper we present an easy-to-implement approach that lends itself to graphical displays of model fit. Our approach involves multiplying the estimated margional residual vector by the Cholesky decomposition of the inverse of the estimated margional variance matrix. The resulting "rotated" residuals are used to construct an empirical cumulative distribution function and pointwise standard errors. The theoretical framework, including conditions and asymptotic properties, involves technical details that are motivated by Lange and …

Censored Linear Regression For Case-Cohort Studies, Bin Nan, Menggang Yu, Jack Kalbfleisch

The University of Michigan Department of Biostatistics Working Paper Series

Right censored data from a classical case-cohort design and a stratified case-cohort design are considered. In the classical case-cohort design, the subcohort is obtained as a simple random sample of the entire cohort, whereas in the stratified design, the subcohort is selected by independent Bernoulli sampling with arbitrary selection probabilities. For each design and under a linear regression model, methods for estimating the regression parameters are proposed and analyzed. These methods are derived by modifying the linear ranks tests and estimating equations that arise from full-cohort data using methods that are similar to the "pseudo-likelihood" estimating equation that has been …

Estimating The Retransformed Mean In A Heteroscedastic Two-Part Model, Alan H. Welsh, Xiao-Hua Zhou

UW Biostatistics Working Paper Series

Two distribution free estimators are proposed to estimate the mean of a dependent variable after fitting a semiparametric two-part heteroscedastic regression model to a transformation of the dependent variable. We show that the proposed estimators are consistent and have asymptotic normal distributions. We also compare their finite-sample performance in a simulation study. Finally, we illustrate the proposed methods in a real-world example of predicting in-patient health care costs.

History-Adjusted Marginal Structural Models And Statically-Optimal Dynamic Treatment Regimes, Mark J. Van Der Laan, Maya L. Petersen

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. These models, introduced by Robins, model the marginal distributions of treatment-specific counterfactual outcomes, possibly conditional on a subset of the baseline covariates. 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 a final time point. However, the utility of these models for some applications has been limited by their inability to incorporate modification of the causal effect of treatment by time-varying covariates. …