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Articles 361 - 390 of 1108
Full-Text Articles in Statistics and Probability
Multiple Testing Of Local Maxima For Detection Of Peaks In Chip-Seq Data, Armin Schwartzman, Andrew Jaffe, Yulia Gavrilov, Clifford A. Meyer
Multiple Testing Of Local Maxima For Detection Of Peaks In Chip-Seq Data, Armin Schwartzman, Andrew Jaffe, Yulia Gavrilov, Clifford A. Meyer
Harvard University Biostatistics Working Paper Series
No abstract provided.
Targeted Maximum Likelihood Estimation Of Natural Direct Effect, Wenjing Zheng, Mark J. Van Der Laan
Targeted Maximum Likelihood Estimation Of Natural Direct Effect, Wenjing Zheng, Mark J. Van Der Laan
U.C. Berkeley Division of Biostatistics Working Paper Series
In many causal inference problems, one is interested in the direct causal effect of an exposure on an outcome of interest that is not mediated by certain intermediate variables. Robins and Greenland (1992) and Pearl (2000) formalized the definition of two types of direct effects (natural and controlled) under the counterfactual framework. Since then, identifiability conditions for these effects have been studied extensively. By contrast, considerably fewer efforts have been invested in the estimation problem of the natural direct effect. In this article, we propose a semiparametric efficient, multiply robust estimator for the natural direct effect of a binary treatment …
On The Covariate-Adjusted Estimation For An Overall Treatment Difference With Data From A Randomized Comparative Clinical Trial, Lu Tian, Tianxi Cai, Lihui Zhao, L. J. Wei
On The Covariate-Adjusted Estimation For An Overall Treatment Difference With Data From A Randomized Comparative Clinical Trial, Lu Tian, Tianxi Cai, Lihui Zhao, L. J. Wei
Harvard University Biostatistics Working Paper Series
No abstract provided.
Targeted Minimum Loss Based Estimation Based On Directly Solving The Efficient Influence Curve Equation, Paul Chaffee, Mark J. Van Der Laan
Targeted Minimum Loss Based Estimation Based On Directly Solving The Efficient Influence Curve Equation, Paul Chaffee, Mark J. Van Der Laan
U.C. Berkeley Division of Biostatistics Working Paper Series
Applying targeted maximum likelihood estimation to longitudinal data can be computationally intensive. As the number of time points and/or number of intermediate factors grows, the computation resources consumed by these algorithms likewise increases. Different TMLE algorithms have different computational speeds and implementation challenges; there may also be efficiency differences of the corresponding estimators. The algorithm we describe here proceeds by solving the empirical efficient influence curve equation directly using numerical computation methods, rather than indirectly (by solving a score equation), which is the usual route. We believe that this estimator is the simplest of the TMLE procedures to implement in …
Variable Importance Analysis With The Multipim R Package, Stephan J. Ritter, Nicholas P. Jewell, Alan E. Hubbard
Variable Importance Analysis With The Multipim R Package, Stephan J. Ritter, Nicholas P. Jewell, Alan E. Hubbard
U.C. Berkeley Division of Biostatistics Working Paper Series
We describe the R package multiPIM, including statistical background, functionality and user options. The package is for variable importance analysis, and is meant primarily for analyzing data from exploratory epidemiological studies, though it could certainly be applied in other areas as well. The approach taken to variable importance comes from the causal inference field, and is different from approaches taken in other R packages. By default, multiPIM uses a double robust targeted maximum likelihood estimator (TMLE) of a parameter akin to the attributable risk. Several regression methods/machine learning algorithms are available for estimating the nuisance parameters of the models, including …
Reduced Bayesian Hierarchical Models: Estimating Health Effects Of Simultaneous Exposure To Multiple Pollutants, Jennifer F. Bobb, Francesca Dominici, Roger D. Peng
Reduced Bayesian Hierarchical Models: Estimating Health Effects Of Simultaneous Exposure To Multiple Pollutants, Jennifer F. Bobb, Francesca Dominici, Roger D. Peng
Johns Hopkins University, Dept. of Biostatistics Working Papers
Quantifying the health effects associated with simultaneous exposure to many air pollutants is now a research priority of the US EPA. Bayesian hierarchical models (BHM) have been extensively used in multisite time series studies of air pollution and health to estimate health effects of a single pollutant adjusted for potential confounding of other pollutants and other time-varying factors. However, when the scientific goal is to estimate the impacts of many pollutants jointly, a straightforward application of BHM is challenged by the need to specify a random-effect distribution on a high-dimensional vector of nuisance parameters, which often do not have an …
A Unified Approach To Non-Negative Matrix Factorization And Probabilistic Latent Semantic Indexing, Karthik Devarajan, Guoli Wang, Nader Ebrahimi
A Unified Approach To Non-Negative Matrix Factorization And Probabilistic Latent Semantic Indexing, Karthik Devarajan, Guoli Wang, Nader Ebrahimi
COBRA Preprint Series
Non-negative matrix factorization (NMF) by the multiplicative updates algorithm is a powerful machine learning method for decomposing a high-dimensional nonnegative matrix V into two matrices, W and H, each with nonnegative entries, V ~ WH. NMF has been shown to have a unique parts-based, sparse representation of the data. The nonnegativity constraints in NMF allow only additive combinations of the data which enables it to learn parts that have distinct physical representations in reality. In the last few years, NMF has been successfully applied in a variety of areas such as natural language processing, information retrieval, image processing, speech recognition …
Multiple Testing Of Local Maxima For Detection Of Unimodal Peaks In 1d, Armin Schwartzman, Yulia Gavrilov, Robert J. Adler
Multiple Testing Of Local Maxima For Detection Of Unimodal Peaks In 1d, Armin Schwartzman, Yulia Gavrilov, Robert J. Adler
Harvard University Biostatistics Working Paper Series
No abstract provided.
Targeted Methods For Finding Quantitative Trait Loci, Hui Wang, Sherri Rose, Mark J. Van Der Laan
Targeted Methods For Finding Quantitative Trait Loci, Hui Wang, Sherri Rose, Mark J. Van Der Laan
U.C. Berkeley Division of Biostatistics Working Paper Series
Conventional genetic mapping methods typically assume parametric models with Gaussian errors, and obtain parameter estimates through maximum likelihood estimation. We propose a general semiparametric model to map quantitative trait loci (QTL) in experimental crosses. In contrast with widely-used interval mapping (IM) derived methods, our model requires fewer assumptions and also accommodates various machine learning algorithms. Estimation using both targeted maximum likelihood and collaborative targeted maximum likelihood methods is compared to a composite interval mapping (CIM) approach. We demonstrate with simulations and real data analyses that, on average, our semiparametric targeted learning approach produces less biased QTL effect estimates than those …
A Bayesian Model Averaging Approach For Observational Gene Expression Studies, Xi Kathy Zhou, Fei Liu, Andrew J. Dannenberg
A Bayesian Model Averaging Approach For Observational Gene Expression Studies, Xi Kathy Zhou, Fei Liu, Andrew J. Dannenberg
COBRA Preprint Series
Identifying differentially expressed (DE) genes associated with a sample characteristic is the primary objective of many microarray studies. As more and more studies are carried out with observational rather than well controlled experimental samples, it becomes important to evaluate and properly control the impact of sample heterogeneity on DE gene finding. Typical methods for identifying DE genes require ranking all the genes according to a pre-selected statistic based on a single model for two or more group comparisons, with or without adjustment for other covariates. Such single model approaches unavoidably result in model misspecification, which can lead to increased error …
When Does Combining Markers Improve Classification Performance And What Are Implications For Practice?, Aasthaa Bansal, Margaret Sullivan Pepe
When Does Combining Markers Improve Classification Performance And What Are Implications For Practice?, Aasthaa Bansal, Margaret Sullivan Pepe
UW Biostatistics Working Paper Series
When an existing standard marker does not have sufficient classification accuracy on its own, new markers are sought with the goal of yielding a combination with better performance. The primary criterion for selecting new markers is that they have good performance on their own and preferably be uncorrelated with the standard. Most often linear combinations are considered. In this paper we investigate the increment in performance that is possible by combining a novel continuous marker with a moderately performing standard continuous marker under a variety of biologically motivated models for their joint distribution. We find that an uncorrelated continuous marker …
Targeted Maximum Likelihood Estimation Of Conditional Relative Risk In A Semi-Parametric Regression Model, Cathy Tuglus, Kristin E. Porter, Mark J. Van Der Laan
Targeted Maximum Likelihood Estimation Of Conditional Relative Risk In A Semi-Parametric Regression Model, Cathy Tuglus, Kristin E. Porter, Mark J. Van Der Laan
U.C. Berkeley Division of Biostatistics Working Paper Series
The conditional relative risk is an important measure in medical and epidemiological studies when the outcome of interest is binary (i.e. disease vs. no disease). When the outcome is common, estimation of conditional relative risk and related parameters can be problematic, especially when the exposure or covariates are continuous. We propose a new estimation procedure based on targeted maximum likelihood methodology that targets the parameters relating to the conditional relative risk for common outcomes under a log-linear, or multiplicative, semi-parametric model. In this paper, we present three possible targeted maximum likelihood estimators for relative risk parameters implied by such a …
Super Learner Based Conditional Density Estimation With Application To Marginal Structural Models, Ivan Diaz Munoz, Mark J. Van Der Laan
Super Learner Based Conditional Density Estimation With Application To Marginal Structural Models, Ivan Diaz Munoz, Mark J. Van Der Laan
U.C. Berkeley Division of Biostatistics Working Paper Series
In this paper we present a histogram-like estimator of a conditional density that uses super learner crossvalidation to estimate the histogram probabilities, as well as the optimal number and position of the bins. This estimator is an alternative to kernel density estimators when the dimension of the problem is large. We demonstrate its applicability to estimation of Marginal Structural Model (MSM) parameters in which an initial estimator of the treatment %mechanism is needed. MSM estimation based on the proposed density estimator results in less biased estimates, when compared to estimates based on a misspecified parametric model.
Comparing Roc Curves Derived From Regression Models, Venkatraman E. Seshan, Mithat Gonen, Colin B. Begg
Comparing Roc Curves Derived From Regression Models, Venkatraman E. Seshan, Mithat Gonen, Colin B. Begg
Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series
In constructing predictive models, investigators frequently assess the incremental value of a predictive marker by comparing the ROC curve generated from the predictive model including the new marker with the ROC curve from the model excluding the new marker. Many commentators have noticed empirically that a test of the two ROC areas often produces a non-significant result when a corresponding Wald test from the underlying regression model is significant. A recent article showed using simulations that the widely-used ROC area test [1] produces exceptionally conservative test size and extremely low power [2]. In this article we show why the ROC …
On Causal Mediation Analysis With A Survival Outcome, Eric J. Tchetgen Tchetgen
On Causal Mediation Analysis With A Survival Outcome, Eric J. Tchetgen Tchetgen
Harvard University Biostatistics Working Paper Series
Suppose that having established a marginal total effect of a point exposure on a time-to-event outcome, an investigator wishes to decompose this effect into its direct and indirect pathways, also know as natural direct and indirect effects, mediated by a variable known to occur after the exposure and prior to the outcome. This paper proposes a theory of estimation of natural direct and indirect effects in two important semiparametric models for a failure time outcome. The underlying survival model for the marginal total effect and thus for the direct and indirect effects, can either be a marginal structural Cox proportional …
Semiparametric Estimation Of Models For Natural Direct And Indirect Effects, Eric J. Tchetgen Tchetgen, Ilya Shpitser
Semiparametric Estimation Of Models For Natural Direct And Indirect Effects, Eric J. Tchetgen Tchetgen, Ilya Shpitser
Harvard University Biostatistics Working Paper Series
In recent years, researchers in the health and social sciences have become increasingly interested in mediation analysis. Specifically, upon establishing a non-null total effect of an exposure, investigators routinely wish to make inferences about the direct (indirect) pathway of the effect of the exposure not through (through) a mediator variable that occurs subsequently to the exposure and prior to the outcome. Natural direct and indirect effects are of particular interest as they generally combine to produce the total effect of the exposure and therefore provide insight on the mechanism by which it operates to produce the outcome. A semiparametric theory …
Semiparametric Theory For Causal Mediation Analysis: Efficiency Bounds, Multiple Robustness, And Sensitivity Analysis, Eric J. Tchetgen Tchetgen, Ilya Shpitser
Semiparametric Theory For Causal Mediation Analysis: Efficiency Bounds, Multiple Robustness, And Sensitivity Analysis, Eric J. Tchetgen Tchetgen, Ilya Shpitser
Harvard University Biostatistics Working Paper Series
Whilst estimation of the marginal (total) causal effect of a point exposure on an outcome is arguably the most common objective of experimental and observational studies in the health and social sciences, in recent years, investigators have also become increasingly interested in mediation analysis. Specifically, upon establishing a non-null total effect of the exposure, investigators routinely wish to make inferences about the direct (indirect) pathway of the effect of the exposure not through (through) a mediator variable that occurs subsequently to the exposure and prior to the outcome. Although powerful semiparametric methodologies have been developed to analyze observational studies, that …
Component Extraction Of Complex Biomedical Signal And Performance Analysis Based On Different Algorithm, Hemant Pasusangai Kasturiwale
Component Extraction Of Complex Biomedical Signal And Performance Analysis Based On Different Algorithm, Hemant Pasusangai Kasturiwale
Johns Hopkins University, Dept. of Biostatistics Working Papers
Biomedical signals can arise from one or many sources including heart ,brains and endocrine systems. Multiple sources poses challenge to researchers which may have contaminated with artifacts and noise. The Biomedical time series signal are like electroencephalogram(EEG),electrocardiogram(ECG),etc The morphology of the cardiac signal is very important in most of diagnostics based on the ECG. The diagnosis of patient is based on visual observation of recorded ECG,EEG,etc, may not be accurate. To achieve better understanding , PCA (Principal Component Analysis) and ICA algorithms helps in analyzing ECG signals . The immense scope in the field of biomedical-signal processing Independent Component Analysis( …
Propensity Score Analysis With Matching Weights, Liang Li
Propensity Score Analysis With Matching Weights, Liang Li
COBRA Preprint Series
The propensity score analysis is one of the most widely used methods for studying the causal treatment effect in observational studies. This paper studies treatment effect estimation with the method of matching weights. This method resembles propensity score matching but offers a number of new features including efficient estimation, rigorous variance calculation, simple asymptotics, statistical tests of balance, clearly identified target population with optimal sampling property, and no need for choosing matching algorithm and caliper size. In addition, we propose the mirror histogram as a useful tool for graphically displaying balance. The method also shares some features of the inverse …
Adaptive Clinical Trial Designs With Pre-Specified Rules For Modifying The Sample Size: Understanding Efficient Types Of Adaptation, Gregory P. Levin, Sarah C. Emerson, Scott S. Emerson
Adaptive Clinical Trial Designs With Pre-Specified Rules For Modifying The Sample Size: Understanding Efficient Types Of Adaptation, Gregory P. Levin, Sarah C. Emerson, Scott S. Emerson
UW Biostatistics Working Paper Series
Methods allowing unplanned adaptations to the sample size based on the interim estimate of treatment effect do not base inference on the minimal sufficient statistic and suffer losses in efficiency when compared to group sequential designs [1, 2, 3]. However, when adaptive sampling plans are completely pre-specified at the design stage of the trial, investigators can proceed with frequentist inference based on the minimal sufficient statistic at the analysis stage. In the context of two general settings where different optimality criteria govern the choice of clinical trial design, we quantify the relative costs and benefits of a variety of fixed …
Evaluation Of Flexible Regression For Non-Unimodal Hazard Functions, Marco Fornili, Patrizia Boracchi, Federico Ambrogi, Elia Biganzoli
Evaluation Of Flexible Regression For Non-Unimodal Hazard Functions, Marco Fornili, Patrizia Boracchi, Federico Ambrogi, Elia Biganzoli
COBRA Preprint Series
Longer follow-up for various kinds of cancer, particularly breast cancer, has made it possible the observation of complex forms of the hazard function of occurrence of metastasis and death. In several studies a bimodal hazard function was obtained, with a possible interpretation in the context of tumor dormancy. The shape of the hazard function is usually estimated by spline regression functions. In the case of breast cancer, no general agreement is obtained on the presence of a complex behavior. This may depend on the properties of the smoothing function adopted. We evaluate through simulations of a bimodal hazard function the …
A General Implementation Of Tmle For Longitudinal Data Applied To Causal Inference In Survival Analysis, Ori M. Stitelman, Victor De Gruttola, Mark J. Van Der Laan
A General Implementation Of Tmle For Longitudinal Data Applied To Causal Inference In Survival Analysis, Ori M. Stitelman, Victor De Gruttola, Mark J. Van Der Laan
U.C. Berkeley Division of Biostatistics Working Paper Series
In many randomized controlled trials the outcome of interest is a time to event, and one measures on each subject baseline covariates and time-dependent covariates until the subject either drops-out, the time to event is observed, or the end of study is reached. The goal of such a study is to assess the causal effect of the treatment on the survival curve. Standard methods (e.g., Kaplan-Meier estimator, Cox-proportional hazards) ignore the available baseline and time-dependent covariates, and are therefore biased if the drop-out is affected by these covariates, and are always inefficient. We present a targeted maximum likelihood estimator of …
A Broad Symmetry Criterion For Nonparametric Validity Of Parametrically-Based Tests In Randomized Trials, Russell T. Shinohara, Constantine E. Frangakis, Constantine G.. Lyketos
A Broad Symmetry Criterion For Nonparametric Validity Of Parametrically-Based Tests In Randomized Trials, Russell T. Shinohara, Constantine E. Frangakis, Constantine G.. Lyketos
Johns Hopkins University, Dept. of Biostatistics Working Papers
Summary. Pilot phases of a randomized clinical trial often suggest that a parametric model may be an accurate description of the trial's longitudinal trajectories. However, parametric models are often not used for fear that they may invalidate tests of null hypotheses of equality between the experimental groups. Existing work has shown that when, for some types of data, certain parametric models are used, the validity for testing the null is preserved even if the parametric models are incorrect. Here, we provide a broader and easier to check characterization of parametric models that can be used to (a) preserve nonparametric validity …
Targeted Minimum Loss Based Estimator That Outperforms A Given Estimator, Susan Gruber, Mark J. Van Der Laan
Targeted Minimum Loss Based Estimator That Outperforms A Given Estimator, Susan Gruber, Mark J. Van Der Laan
U.C. Berkeley Division of Biostatistics Working Paper Series
Targeted minimum loss based estimation (TMLE) provides a template for the construction of semiparametric locally efficient double robust substitution estimators of the target parameter of the data generating distribution in a semiparametric censored data or causal inference model (van der Laan and Rubin (2006),van der Laan (2008), van der Laan and Rose (2011)). In this article we demonstrate how to construct a TMLE that also satisfies the property that it is at least as efficient as a user supplied asymptotically linear estimator. For the sake of illustration we focus on estimation of the additive average causal effect of a point …
The Relative Performance Of Targeted Maximum Likelihood Estimators, Kristin E. Porter, Susan Gruber, Mark J. Van Der Laan, Jasjeet S. Sekhon
The Relative Performance Of Targeted Maximum Likelihood Estimators, Kristin E. Porter, Susan Gruber, Mark J. Van Der Laan, Jasjeet S. Sekhon
U.C. Berkeley Division of Biostatistics Working Paper Series
There is an active debate in the literature on censored data about the relative performance of model based maximum likelihood estimators, IPCW-estimators, and a variety of double robust semiparametric efficient estimators. Kang and Schafer (2007) demonstrate the fragility of double robust and IPCW-estimators in a simulation study with positivity violations. They focus on a simple missing data problem with covariates where one desires to estimate the mean of an outcome that is subject to missingness. Responses by Robins et al. (2007), Tsiatis and Davidian (2007), Tan (2007a) and Ridgeway and McCaffrey (2007) further explore the challenges faced by double robust …
Estimation And Testing In Targeted Group Sequential Covariate-Adjusted Randomized Clinical Trials, Antoine Chambaz, Mark J. Van Der Laan
Estimation And Testing In Targeted Group Sequential Covariate-Adjusted Randomized Clinical Trials, Antoine Chambaz, Mark J. Van Der Laan
U.C. Berkeley Division of Biostatistics Working Paper Series
This article is devoted to the construction and asymptotic study of adaptive group sequential covariate-adjusted randomized clinical trials analyzed through the prism of the semiparametric methodology of targeted maximum likelihood estimation (TMLE). We show how to build, as the data accrue group-sequentially, a sampling design which targets a user-supplied optimal design. We also show how to carry out a sound TMLE statistical inference based on such an adaptive sampling scheme (therefore extending some results known in the i.i.d setting only so far), and how group-sequential testing applies on top of it. The procedure is robust (i.e., consistent even if the …
Subsample Ignorable Likelihood For Accelerated Failure Time Models With Missing Predictors, Nanhua Zhang, Roderick J. Little
Subsample Ignorable Likelihood For Accelerated Failure Time Models With Missing Predictors, Nanhua Zhang, Roderick J. Little
The University of Michigan Department of Biostatistics Working Paper Series
No abstract provided.
Targeted Maximum Likelihood Estimation For Dynamic Treatment Regimes In Sequential Randomized Controlled Trials, Paul Chaffee, Mark J. Van Der Laan
Targeted Maximum Likelihood Estimation For Dynamic Treatment Regimes In Sequential Randomized Controlled Trials, Paul Chaffee, Mark J. Van Der Laan
U.C. Berkeley Division of Biostatistics Working Paper Series
Sequential Randomized Controlled Trials (SRCTs) are rapidly becoming essential tools in the search for optimized treatment regimes in ongoing treatment settings. Analyzing data for multiple time-point treatments with a view toward optimal treatment regimes is of interest in many types of afflictions: HIV infection, Attention Deficit Hyperactivity Disorder in children, leukemia, prostate cancer, renal failure, and many others. Methods for analyzing data from SRCTs exist but they are either inefficient or suffer from the drawbacks of estimating equation methodology. We describe an estimation procedure, targeted maximum likelihood estimation (TMLE), which has been fully developed and implemented in point treatment settings, …
Threshold Regression Models Adapted To Case-Control Studies, And The Risk Of Lung Cancer Due To Occupational Exposure To Asbestos In France, Antoine Chambaz, Dominique Choudat, Catherine Huber, Jean-Claude Pairon, Mark J. Van Der Laan
Threshold Regression Models Adapted To Case-Control Studies, And The Risk Of Lung Cancer Due To Occupational Exposure To Asbestos In France, Antoine Chambaz, Dominique Choudat, Catherine Huber, Jean-Claude Pairon, Mark J. Van Der Laan
U.C. Berkeley Division of Biostatistics Working Paper Series
Asbestos has been known for many years as a powerful carcinogen. Our purpose is quantify the relationship between an occupational exposure to asbestos and an increase of the risk of lung cancer. Furthermore, we wish to tackle the very delicate question of the evaluation, in subjects suffering from a lung cancer, of how much the amount of exposure to asbestos explains the occurrence of the cancer. For this purpose, we rely on a recent French case-control study. We build a large collection of threshold regression models, data-adaptively select a better model in it by multi-fold likelihood-based cross-validation, then fit the …
Estimating Subject-Specific Treatment Differences For Risk-Benefit Assessment With Competing Risk Event-Time Data, Brian Claggett, Lihui Zhao, Lu Tian, Davide Castagno, L. J. Wei
Estimating Subject-Specific Treatment Differences For Risk-Benefit Assessment With Competing Risk Event-Time Data, Brian Claggett, Lihui Zhao, Lu Tian, Davide Castagno, L. J. Wei
Harvard University Biostatistics Working Paper Series
No abstract provided.