Statistical Models Commons^™

Direct Effect Models, Mark J. Van Der Laan, Maya L. Petersen

U.C. Berkeley Division of Biostatistics Working Paper Series

The causal effect of a treatment on an outcome is generally mediated by several intermediate variables. Estimation of the component of the causal effect of a treatment that is mediated by a given intermediate variable (the indirect effect of the treatment), and the component that is not mediated by that intermediate variable (the direct effect of the treatment) is often relevant to mechanistic understanding and to the design of clinical and public health interventions. Under the assumption of no-unmeasured confounders for treatment and the intermediate variable, Robins & Greenland (1992) define an individual direct effect as the counterfactual effect of …

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 …

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 …

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 …

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 …

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 …

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. …

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

UW Biostatistics Working Paper Series

We compare simple logistic regression with an alternative robust procedure for constructing linear predictors to be used for the two state classification task. Theoritical advantages of the robust procedure over logistic regression are: (i) although it assumes a generalized linear model for the dichotomous outcome variable, it does not require specification of the link function; (ii) it accommodates case-control designs even when the model is not logistic; and (iii) it yields sensible results even when the generalized linear model assumption fails to hold. Surprisingly, we find that the linear predictor derived from the logistic regression likelihood is very robust in …

Seasonal Analyses Of Air Pollution And Mortality In 100 U.S. Cities, Roger D. Peng, Francesca Dominici, Roberto Pastor-Barriuso, Scott L. Zeger, Jonathan M. Samet

Johns Hopkins University, Dept. of Biostatistics Working Papers

Time series models relating short-term changes in air pollution levels to daily mortality counts typically assume that the effects of air pollution on the log relative rate of mortality do not vary with time. However, these short-term effects might plausibly vary by season. Changes in the sources of air pollution and meteorology can result in changes in characteristics of the air pollution mixture across seasons. The authors develop Bayesian semi-parametric hierarchical models for estimating time-varying effects of pollution on mortality in multi-site time series studies. The methods are applied to the updated National Morbidity and Mortality Air Pollution Study database …

On Corrected Score Approach For Proportional Hazards Model With Covariate Measurement Error, Xiao Song, Yijian Huang

UW Biostatistics Working Paper Series

In the presence of covariate measurement error with the proportional hazards model, several functional modeling methods have been proposed. These include the conditional score estimator (Tsiatis and Davidian, 2001), the parametric correction estimator (Nakamura, 1992) and the nonparametric correction estimator (Huang and Wang, 2000, 2003) in the order of weaker assumptions on the error. Although they are all consistent, each suffers from potential difficulties with small samples and substantial measurement error. In this article, upon noting that the conditional score and parametric correction estimators are asymptotically equivalent in the case of normal error, we investigate their relative finite sample performance …

Overlap Bias In The Case-Crossover Design, With Application To Air Pollution Exposures, Holly Janes, Lianne Sheppard, Thomas Lumley

UW Biostatistics Working Paper Series

The case-crossover design uses cases only, and compares exposures just prior to the event times to exposures at comparable control, or “referent” times, in order to assess the effect of short-term exposure on the risk of a rare event. It has commonly been used to study the effect of air pollution on the risk of various adverse health events. Proper selection of referents is crucial, especially with air pollution exposures, which are shared, highly seasonal, and often have a long term time trend. Hence, careful referent selection is important to control for time-varying confounders, and in order to ensure that …

Uncertainty And The Value Of Diagnostic Information With Application To Axillary Lymph Node Dissection In Breast Cancer, Giovanni Parmigiani

Johns Hopkins University, Dept. of Biostatistics Working Papers

In clinical decision making, it is common to ask whether, and how much, a diagnostic procedure is contributing to subsequent treatment decisions. Statistically, quantification of the value of the information provided by a diagnostic procedure can be carried out using decision trees with multiple decision points, representing both the diagnostic test and the subsequent treatments that may depend on the test's results. This article investigates probabilistic sensitivity analysis approaches for exploring and communicating parameter uncertainty in such decision trees. Complexities arise because uncertainty about a model's inputs determines uncertainty about optimal decisions at all decision nodes of a tree. We …

Survival Model Predictive Accuracy And Roc Curves, Patrick Heagerty, Yingye Zheng

UW Biostatistics Working Paper Series

The predictive accuracy of a survival model can be summarized using extensions of the proportion of variation explained by the model, or R^2, commonly used for continuous response models, or using extensions of sensitivity and specificity which are commonly used for binary response models.

In this manuscript we propose new time-dependent accuracy summaries based on time-specific versions of sensitivity and specificity calculated over risk sets. We connect the accuracy summaries to a previously proposed global concordance measure which is a variant of Kendall's tau. In addition, we show how standard Cox regression output can be used to obtain estimates of …

Time-Series Studies Of Particulate Matter, Michelle L. Bell, Jonathan M. Samet, Francesca Dominici

Johns Hopkins University, Dept. of Biostatistics Working Papers

Studies of air pollution and human health have evolved from descriptive studies of the early phenomena of large increases in adverse health effects following extreme air pollution episodes, to time-series analyses and the development of sophisticated regression models. In fact, advanced statistical methods are necessary to address the many challenges inherent in the detection of a small pollution risk in the presence of many confounders. This paper reviews the history, methods, and findings of the time-series studies estimating health risks associated with short-term exposure to particulate matter, though much of the discussion is applicable to epidemiological studies of air pollution …

A Corrected Pseudo-Score Approach For Additive Hazards Model With Longitudinal Covariates Measured With Error, Xiao Song, Yijian Huang

UW Biostatistics Working Paper Series

In medical studies, it is often of interest to characterize the relationship between a time-to-event and covariates, not only time-independent but also time-dependent. Time-dependent covariates are generally measured intermittently and with error. Recent interests focus on the proportional hazards framework, with longitudinal data jointly modeled through a mixed effects model. However, approaches under this framework depend on the normality assumption of the error, and might encounter intractable numerical difficulties in practice. This motivates us to consider an alternative framework, that is, the additive hazards model, under which little has been done when time-dependent covariates are measured with error. We propose …

An Extended General Location Model For Causal Inference From Data Subject To Noncompliance And Missing Values, Yahong Peng, Rod Little, Trivellore E. Raghuanthan

The University of Michigan Department of Biostatistics Working Paper Series

Noncompliance is a common problem in experiments involving randomized assignment of treatments, and standard analyses based on intention-to treat or treatment received have limitations. An attractive alternative is to estimate the Complier-Average Causal Effect (CACE), which is the average treatment effect for the subpopulation of subjects who would comply under either treatment (Angrist, Imbens and Rubin, 1996, henceforth AIR). We propose an Extended General Location Model to estimate the CACE from data with non-compliance and missing data in the outcome and in baseline covariates. Models for both continuous and categorical outcomes and ignorable and latent ignorable (Frangakis and Rubin, 1999) …

Estimating The Accuracy Of Polymerase Chain Reaction-Based Tests Using Endpoint Dilution, Jim Hughes, Patricia Totten

UW Biostatistics Working Paper Series

PCR-based tests for various microorganisms or target DNA sequences are generally acknowledged to be highly "sensitive" yet the concept of sensitivity is ill-defined in the literature on these tests. We propose that sensitivity should be expressed as a function of the number of target DNA molecules in the sample (or specificity when the target number is 0). However, estimating this "sensitivity curve" is problematic since it is difficult to construct samples with a fixed number of targets. Nonetheless, using serially diluted replicate aliquots of a known concentration of the target DNA sequence, we show that it is possible to disentangle …

Analysis Of Longitudinal Marginal Structural Models , Jennifer F. Bryan, Zhuo Yu, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

In this article we construct and study estimators of the causal effect of a time-dependent treatment on survival in longitudinal studies. We employ a particular marginal structural model (MSM), and follow a general methodology for constructing estimating functions in censored data models. The inverse probability of treatment weighted (IPTW) estimator is used as an initial estimator and the corresponding treatment-orthogonalized, one-step estimator is consistent and asymptotically linear when the treatment mechanism is consistently estimated. We extend these methods to handle informative censoring. A simulation study demonstrates that the the treatment-orthogonalized, one-step estimator is superior to the IPTW estimator in terms …

An Empirical Study Of Marginal Structural Models For Time-Independent Treatment, Tanya A. Henneman, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

In non-randomized treatment studies a significant problem for statisticians is determining how best to adjust for confounders. Marginal structural models (MSMs) and inverse probability of treatment weighted (IPTW) estimators are useful in analyzing the causal effect of treatment in observational studies. Given an IPTW estimator a doubly robust augmented IPTW (AIPTW) estimator orthogonalizes it resulting in a more e±cient estimator than the IPTW estimator. One purpose of this paper is to make a practical comparison between the IPTW estimator and the doubly robust AIPTW estimator via a series of Monte- Carlo simulations. We also consider the selection of the optimal …

Estimating Causal Parameters In Marginal Structural Models With Unmeasured Confounders Using Instrumental Variables, Tanya A. Henneman, Mark Johannes Van Der Laan, Alan E. Hubbard

U.C. Berkeley Division of Biostatistics Working Paper Series

For statisticians analyzing medical data, a significant problem in determining the causal effect of a treatment on a particular outcome of interest, is how to control for unmeasured confounders. Techniques using instrumental variables (IV) have been developed to estimate causal parameters in the presence of unmeasured confounders. In this paper we apply IV methods to both linear and non-linear marginal structural models. We study a specific class of generalized estimating equations that is appropriate to these data, and compare the performance of the resulting estimator to the standard IV method, a two-stage least squares procedure. Our results are applied to …