Longitudinal Data Analysis and Time Series Commons^™

Studying The Optimal Scheduling For Controlling Prostate Cancer Under Intermittent Androgen Suppression, Sunil K. Dhar, Hans R. Chaudhry, Bruce G. Bukiet, Zhiming Ji, Nan Gao, Thomas W. Findley

Harvard University Biostatistics Working Paper Series

This retrospective study shows that the majority of patients’ correlations between PSA and Testosterone during the on-treatment period is at least 0.90. Model-based duration calculations to control PSA levels during off-treatment are provided. There are two pairs of models. In one pair, the Generalized Linear Model and Mixed Model are both used to analyze the variability of PSA at the individual patient level by using the variable “Patient ID” as a repeated measure. In the second pair, Patient ID is not used as a repeated measure but additional baseline variables are included to analyze the variability of PSA.

Methods For Dealing With Death And Missing Data, And For Standardizing Different Health Variables In Longitudinal Datasets: The Cardiovascular Health Study, Paula Diehr

UW Biostatistics Working Paper Series

Longitudinal studies of older adults usually need to account for deaths and missing data. The study databases often include multiple health-related variables, whose trends over time are hard to compare because they were measured on different scales. Here we present a unified approach to these three problems that was developed and used in the Cardiovascular Health Study. Data were first transformed to a new scale that had integer/ratio properties, and on which “dead” logically takes the value zero. Missing data were then imputed on this new scale, using each person’s own data over time. Imputation could thus be informed by …

Evaluating The Impact Of A Hiv Low-Risk Express Care Task-Shifting Program: A Case Study Of The Targeted Learning Roadmap, Linh Tran, Constantin T. Yiannoutsos, Beverly S. Musick, Kara K. Wools-Kaloustian, Abraham Siika, Sylvester Kimaiyo, Mark J. Van Der Laan, Maya L. Petersen

U.C. Berkeley Division of Biostatistics Working Paper Series

In conducting studies on an exposure of interest, a systematic roadmap should be applied for translating causal questions into statistical analyses and interpreting the results. In this paper we describe an application of one such roadmap applied to estimating the joint effect of both time to availability of a nurse-based triage system (low risk express care (LREC)) and individual enrollment in the program among HIV patients in East Africa. Our study population is comprised of 16;513 subjects found eligible for this task-shifting program within 15 clinics in Kenya between 2006 and 2009, with each clinic starting the LREC program between …

Models For Hsv Shedding Must Account For Two Levels Of Overdispersion, Amalia Magaret

UW Biostatistics Working Paper Series

We have frequently implemented crossover studies to evaluate new therapeutic interventions for genital herpes simplex virus infection. The outcome measured to assess the efficacy of interventions on herpes disease severity is the viral shedding rate, defined as the frequency of detection of HSV on the genital skin and mucosa. We performed a simulation study to ascertain whether our standard model, which we have used previously, was appropriately considering all the necessary features of the shedding data to provide correct inference. We simulated shedding data under our standard, validated assumptions and assessed the ability of 5 different models to reproduce the …

Mediation Analysis With Time-Varying Exposures And Mediators, Tyler J. Vanderweele, Eric Tchetgen Tchetgen

Harvard University Biostatistics Working Paper Series

In this paper we consider mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are no time-varying confounders affected by prior exposure and mediator values, identification of direct and indirect effects is achieved by a longitudinal version of Pearl's mediation formula. When there are time-varying confounders affected …

Set-Based Tests For Genetic Association In Longitudinal Studies, Zihuai He, Min Zhang, Seunggeun Lee, Jennifer A. Smith, Xiuqing Guo, Walter Palmas, Sharon L.R. Kardia, Ana V. Diez Roux, Bhramar Mukherjee

The University of Michigan Department of Biostatistics Working Paper Series

Genetic association studies with longitudinal markers of chronic diseases (e.g., blood pressure, body mass index) provide a valuable opportunity to explore how genetic variants affect traits over time by utilizing the full trajectory of longitudinal outcomes. Since these traits are likely influenced by the joint effect of multiple variants in a gene, a joint analysis of these variants considering linkage disequilibrium (LD) may help to explain additional phenotypic variation. In this article, we propose a longitudinal genetic random field model (LGRF), to test the association between a phenotype measured repeatedly during the course of an observational study and a set …

Multi-State Models For Natural History Of Disease, Amy Laird, Rebecca A. Hubbard, Lurdes Y. T. Inoue

UW Biostatistics Working Paper Series

Longitudinal studies are a useful tool for investigating the course of chronic diseases. Many chronic diseases can be characterized by a set of health states. We can improve our understanding of the natural history of the disease by modeling the sequence of visited health states and the duration in each state. However, in most applications, subjects are observed only intermittently. This observation scheme creates a major modeling challenge: the transition times are not known exactly, and in some cases the path through the health states is not known.

In this manuscript we review existing approaches for modeling multi-state longitudinal data. …

Targeted Maximum Likelihood Estimation For Dynamic And Static Longitudinal Marginal Structural Working Models, Maya L. Petersen, Joshua Schwab, Susan Gruber, Nello Blaser, Michael Schomaker, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

This paper describes a targeted maximum likelihood estimator (TMLE) for the parameters of longitudinal static and dynamic marginal structural models. We consider a longitudinal data structure consisting of baseline covariates, time-dependent intervention nodes, intermediate time-dependent covariates, and a possibly time dependent outcome. The intervention nodes at each time point can include a binary treatment as well as a right-censoring indicator. Given a class of dynamic or static interventions, a marginal structural model is used to model the mean of the intervention specific counterfactual outcome as a function of the intervention, time point, and possibly a subset of baseline covariates. Because …

Modeling Criminal Careers As Departures From A Unimodal Population Age-Crime Curve: The Case Of Marijuana Use, Donatello Telesca, Elena Erosheva, Derek Kreager, Ross Matsueda

COBRA Preprint Series

A major aim of longitudinal analyses of life course data is to describe the within- and between-individual variability in a behavioral outcome, such as crime. Statistical analyses of such data typically draw on mixture and mixed-effects growth models. In this work, we present a functional analytic point of view and develop an alternative method that models individual crime trajectories as departures from a population age-crime curve. Drawing on empirical and theoretical claims in criminology, we assume a unimodal population age-crime curve and allow individual expected crime trajectories to differ by their levels of offending and patterns of temporal misalignment. We …

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, …

Estimating Temporal Associations In Electrocorticographic (Ecog) Time Series With First Order Pruning, Haley Hedlin, Dana Boatman, Brian Caffo

Johns Hopkins University, Dept. of Biostatistics Working Papers

Granger causality (GC) is a statistical technique used to estimate temporal associations in multivariate time series. Many applications and extensions of GC have been proposed since its formulation by Granger in 1969. Here we control for potentially mediating or confounding associations between time series in the context of event-related electrocorticographic (ECoG) time series. A pruning approach to remove spurious connections and simultaneously reduce the required number of estimations to fit the effective connectivity graph is proposed. Additionally, we consider the potential of adjusted GC applied to independent components as a method to explore temporal relationships between underlying source signals. Both …

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 …

Modeling Menstrual Cycle Length And Variability At The Approach Of Menopause Using Bayesian Changepoint Models, Xiaobi Huang, Michael R. Elliott, Sioban D. Harlow

The University of Michigan Department of Biostatistics Working Paper Series

As women approach menopause, the patterns of their menstruation cycle lengths change. To study these changes, we need to jointly model both the mean and variability of the cycle length. The model incorporates separate mean and variance change points for each woman and a hierarchical model to link them together, along with regression components to include predictors of menopausal onset such as age at menarche and parity. Data are from TREMIN, an ongoing 70-year old longitudinal study that has obtained menstrual calendar data of women throughout their reproductive life course. An additional complexity arises from the fact that these calendars …

Panel Count Data Regression With Informative Observation Times, Petra Buzkova

UW Biostatistics Working Paper Series

When patients are monitored for potentially recurrent events such as infections or tumor metastases, it is common for clinicians to ask patients to come back sooner for follow-up based on the results of the most recent exam. This means that subjects’ observation times will be irregular and related to subject-specific factors. Previously proposed methods for handling such panel count data assume that the dependence between the events process and the observation time process is time-invariant. This article considers situations where the observation times are predicted by time-varying factors, such as the outcome observed at the last visit or cumulative exposure. …

Modeling Multilevel Sleep Transitional Data Via Poisson Log-Linear Multilevel Models, Bruce J. Swihart, Brian Caffo, Ciprian Crainiceanu, Naresh M. Punjabi

Johns Hopkins University, Dept. of Biostatistics Working Papers

This paper proposes Poisson log-linear multilevel models to investigate population variability in sleep state transition rates. We specifically propose a Bayesian Poisson regression model that is more flexible, scalable to larger studies, and easily fit than other attempts in the literature. We further use hierarchical random effects to account for pairings of individuals and repeated measures within those individuals, as comparing diseased to non-diseased subjects while minimizing bias is of epidemiologic importance. We estimate essentially non-parametric piecewise constant hazards and smooth them, and allow for time varying covariates and segment of the night comparisons. The Bayesian Poisson regression is justified …

Lasagna Plots: A Saucy Alternative To Spaghetti Plots, Bruce Swihart, Brian Caffo, Bryan D. James, Matthew Strand, Brian S. Schwartz, Naresh M. Punjabi

Johns Hopkins University, Dept. of Biostatistics Working Papers

Longitudinal repeated measures data has often been visualized with spaghetti plots for continuous out- comes. For large datasets, this often leads to over-plotting and consequential obscuring of trends in the data. This is primarily due to overlapping of trajectories. Here, we suggest a framework called lasagna plot ting that constrains the subject-specific trajectories to prevent overlapping and utilizes gradients of color to depict the outcome. Dynamic sorting and visualization is demonstrated as an exploratory data analysis tool. Supplemental material in the form of sample R code additional illustrated examples are available online.

Modeling Multilevel Sleep Transitional Data Via Poisson Log-Linear Multilevel Models, Bruce J. Swihart

COBRA Preprint Series

This paper proposes Poisson log-linear multilevel models to investigate population variability in sleep state transition rates. We specifically propose a Bayesian Poisson regression model that is more flexible, scalable to larger studies, and easily fit than other attempts in the literature. We further use hierarchical random effects to account for pairings of individuals and repeated measures within those individuals, as comparing diseased to non-diseased subjects while minimizing bias is of epidemiologic importance. We estimate essentially non-parametric piecewise constant hazards and smooth them, and allow for time varying covariates and segment of the night comparisons. The Bayesian Poisson regression is justified …

Reliability Of The Model For Clustering Of Longitudinal Datasets Of Infant Mortality Rate In India, Ajay Kumar Bansal, S D. Sharma

COBRA Preprint Series

Because of the natural tendency of human beings and heavenly bodies to form groups, the technique of cluster analysis or segmentation analysis find its importance and applications in many fields of study. A model for clustering of time trends was proposed by authors whose beauty is that 2-way dimensions that is the horizontal flow of the trend and vertical distance of the trend from a common base are considered to obtain the natural clusters. In the present paper, the reliability of this model is studied in two steps namely (i) by repeating the analysis but using different interval distance measures …

Spatial Cluster Detection For Repeatedly Measured Outcomes While Accounting For Residential History, Andrea J. Cook, Diane Gold, Yi Li

Harvard University Biostatistics Working Paper Series

No abstract provided.

Spatial Cluster Detection For Weighted Outcomes Using Cumulative Geographic Residuals, Andrea J. Cook, Yi Li, David Arterburn, Ram C. Tiwari

Harvard University Biostatistics Working Paper Series

No abstract provided.

Bayesian Model Averaging For Clustered Data: Imputing Missing Daily Air Pollution Concentration, Howard H. Chang, Francesca Dominici, Roger D. Peng

Johns Hopkins University, Dept. of Biostatistics Working Papers

The presence of missing observations is a challenge in statistical analysis especially when data are clustered. In this paper, we develop a Bayesian model averaging (BMA) approach for imputing missing observations in clustered data. Our approach extends BMA by allowing the weights of competing regression models for missing data imputation to vary between clusters while borrowing information across clusters in estimating model parameters. Through simulation and cross-validation studies, we demonstrate that our approach outperforms the standard BMA imputation approach where model weights are assumed to be the same for all clusters. We then apply our proposed method to a national …

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 …

A Functional Random Effects Model For Flexible Assessment Of Susceptibility In Longitudinal Designs, Brent A. Coull

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.

"%Qls Sas Macro: A Sas Macro For Analysis Of Longitudinal Data Using Quasi-Least Squares"., Hanjoo Kim, Justine Shults

UPenn Biostatistics Working Papers

Quasi-least squares (QLS) is an alternative computational approach for estimation of the correlation parameter in the framework of generalized estimating equations (GEE). QLS overcomes some limitations of GEE that were discussed in Crowder (Biometrika 82 (1995) 407-410). In addition, it allows for easier implementation of some correlation structures that are not available for GEE. We describe a user written SAS macro called %QLS, and demonstrate application of our macro using a clinical trial example for the comparison of two treatments for a common toenail infection. %QLS also computes the lower and upper boundaries of the correlation parameter for analysis of …

Joint Spatial Modeling Of Recurrent Infection And Growth With Processes Under Intermittent Observation, Farouk S. Nathoo

COBRA Preprint Series

In this article we present new statistical methodology for longitudinal studies in forestry where trees are subject to recurrent infection and the hazard of infection depends on tree growth over time. Understanding the nature of this dependence has important implications for reforestation and breeding programs. Challenges arise for statistical analysis in this setting with sampling schemes leading to panel data, exhibiting dynamic spatial variability, and incomplete covariate histories for hazard regression. In addition, data are collected at a large number of locations which poses computational difficulties for spatiotemporal modeling. A joint model for infection and growth is developed; wherein, a …

On The Designation Of The Patterned Associations For Longitudinal Bernoulli Data: Weight Matrix Versus True Correlation Structure?, Hanjoo Kim, Joseph M. Hilbe, Justine Shults

UPenn Biostatistics Working Papers

Due to potential violation of standard constraints for the correlation for binary data, it has been argued recently that the working correlation matrix should be viewed as a weight matrix that should not be confused with the true correlation structure. We propose two arguments to support our view to the contrary for the first-order autoregressive AR(1) correlation matrix. First, we prove that the standard constraints are not unduly restrictive for the AR(1) structure that is plausible for longitudinal data; furthermore, for the logit link function the upper boundary value only depends on the regression parameter and the change in covariate …

Decomposition Of Regression Estimators To Explore The Influence Of "Unmeasured" Time-Varying Confounders, Yun Lu, Scott L. Zeger

Johns Hopkins University, Dept. of Biostatistics Working Papers

In environmental epidemiology, exposure X and health outcome Y vary in space and time. We present a method to diagnose the possible influence of unmeasured confounders U on the estimated effect of X on Y and to propose several approaches to robust estimation. The idea is to use space and time as proxy measures for the unmeasured factors U. We start with the time series case where X and Y are continuous variables at equally-spaced times and assume a linear model. We define matching estimator b(u)s that correspond to pairs of observations with specific lag u. Controlling for a smooth …

Detailed Version: Analyzing Direct Effects In Randomized Trials With Secondary Interventions: An Application To Hiv Prevention Trials, Michael A. Rosenblum, Nicholas P. Jewell, Mark J. Van Der Laan, Stephen Shiboski, Ariane Van Der Straten, Nancy Padian

U.C. Berkeley Division of Biostatistics Working Paper Series

This is the detailed technical report that accompanies the paper “Analyzing Direct Effects in Randomized Trials with Secondary Interventions: An Application to HIV Prevention Trials” (an unpublished, technical report version of which is available online at http://www.bepress.com/ucbbiostat/paper223).

The version here gives full details of the models for the time-dependent analysis, and presents further results in the data analysis section. The Methods for Improving Reproductive Health in Africa (MIRA) trial is a recently completed randomized trial that investigated the effect of diaphragm and lubricant gel use in reducing HIV infection among susceptible women. 5,045 women were randomly assigned to either the …