Longitudinal Data Analysis and Time Series Commons^™

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 …

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 …

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 …

Individualized Predictions Of Disease Progression Following Radiation Therapy For Prostate Cancer., Jeremy Taylor, Menggang Yu, Howard M. Sandler

The University of Michigan Department of Biostatistics Working Paper Series

Background: Following treatment for localized prostate cancer, men are monitored with serial PSA measurements. Refining the predictive value of post-treatment PSA determinations may add to clinical management and we have developed a model that predicts for an individual patient future PSA values and estimates the time to future clinical recurrence.

Methods: Data from 934 patients treated for prostate cancer between 1987 and 2000 were used to develop a comprehensive statistical model to fit the clinical recurrence events and pattern of PSA data. A logistic regression model was used for the probability of cure, non-linear hierarchical mixed models were used for …

Individual Prediction In Prostate Cancer Studies Using A Joint Longitudinal-Survival-Cure Model, Menggang Yu, Jeremy Taylor, Howard M. Sandler

The University of Michigan Department of Biostatistics Working Paper Series

For monitoring patients treated for prostate cancer, Prostate Specific Antigen (PSA) is measured periodically after they receive treatment. Increases in PSA are suggestive of recurrence of the cancer and are used in making decisions about possible new treatments. The data from studies of such patients typically consist of longitudinal PSA measurements, censored event times and baseline covariates. Methods for the combined analysis of both longitudinal and survival data have been developed in recent years, with the main emphasis being on modeling and estimation. We analyze data from a prostate cancer study that has been extended by adding a mixture structure …

Equivalent Kernels Of Smoothing Splines In Nonparametric Regression For Clustered/Longitudinal Data, Xihong Lin, Naisyin Wang, Alan H. Welsh, Raymond J. Carroll

The University of Michigan Department of Biostatistics Working Paper Series

We compare spline and kernel methods for clustered/longitudinal data. For independent data, it is well known that kernel methods and spline methods are essentially asymptotically equivalent (Silverman, 1984). However, the recent work of Welsh, et al. (2002) shows that the same is not true for clustered/longitudinal data. First, conventional kernel methods fail to account for the within- cluster correlation, while spline methods are able to account for this correlation. Second, kernel methods and spline methods were found to have different local behavior, with conventional kernels being local and splines being non-local. To resolve these differences, we show that a smoothing …

Histospline Method In Nonparametric Regression Models With Application To Clustered/Longitudinal Data, Raymond J. Carroll, Peter Hall, Tatiyana V. Apanasovich, Xihong Lin

The University of Michigan Department of Biostatistics Working Paper Series

Kernel and smoothing methods for nonparametric function and curve estimation have been particularly successful in "standard" settings, where function values are observed subject to independent errors. However, when aspects of the function are known parametrically, or where the sampling scheme has significant structure, it can be quite difficult to adapt standard methods in such a way that they retain good statistical performance and continue to enjoy easy computability and good numerical properties. In particular, when using local linear modeling it is often awkward to both respect the sampling scheme and produce an estimator with good variance properties, without resorting to …

Efficient Semiparametric Marginal Estimation For Longitudinal/Clustered Data, Naisyin Wang, Raymond J. Carroll, Xihong Lin

The University of Michigan Department of Biostatistics Working Paper Series

We consider marginal generalized semiparametric partially linear models for clustered data. Lin and Carroll (2001a) derived the semiparametric efficinet score funtion for this problem in the mulitvariate Gaussian case, but they were unable to contruct a semiparametric efficient estimator that actually achieved the semiparametric information bound. We propose such an estimator here and generalize the work to marginal generalized partially liner models. Asymptotic relative efficincies of the estimation or throughout are investigated. The finite sample performance of these estimators is evaluated through simulations and illustrated using a longtiudinal CD4 count data set. Both theoretical and numerical results indicate that properly …

A Varying-Coefficient Cox Model For The Effect Of Age At A Marker Event On Age At Menopause, Bin Nan, Xihong Lin, Lynda D. Lisabeth, Sioban D. Harlow

The University of Michigan Department of Biostatistics Working Paper Series

. It is of recent interest in reproductive health research to investigate the validity of a marker event for the onset of menopausal transition and to estimate age at menopause using age at the marker event. We propose a varying coefficient Cox model to investigate the association between age at a marker event, denned as a specific bleeding pattern change, and age at menopause, where both events are subject to censoring and their association varies with age at the marker event. Estimation proceeds using the regression spline method. The proposed method is applied to the Tremin Trust Data to evaluate …

Mixtures Of Varying Coefficient Models For Longitudinal Data With Discrete Or Continuous Non-Ignorable Dropout, Joseph W. Hogan, Xihong Lin, Benjamin A. Herman

The University of Michigan Department of Biostatistics Working Paper Series

The analysis of longitudinal repeated measures data is frequently complicated by missing data due to informative dropout. We describe a mixture model for joint distribution for longitudinal repeated measures, where the dropout distribution may be continuous and the dependence between response and dropout is semiparametric. Specifically, we assume that responses follow a varying coefficient random effects model conditional on dropout time, where the regression coefficients depend on dropout time through unspecified nonparametric functions that are estimated using step functions when dropout time is discrete (e.g., for panel data) and using smoothing splines when dropout time is continuous. Inference under the …