Regression analysis of correlated interval-censored failure time data with a cured subgroup

Interval-censored failure time data commonly occur in many periodic follow-up studies such as epidemiological experiments, medical studies and clinical trials. By intervalcensored data, we usually mean that one cannot observe the failure time of interest and instead we know that it belongs to a time interval. Correlated failure time data commonly occur when there are multiple events on one individual or when the study subjects are clustered into some small groups. In this situation, study subjects from same subgroup or the failure events from same individuals are usually regarded as dependent, but the subjects in different clusters or failure events from different individuals are assumed to be independent. Besides the correlation between the cluster, sometimes the cluster size may be informative or carry some information about the failure time of interest. Cured subgroup is another interesting topic that has been discussed by many authors. For this situation, unlike the assumptions in traditional survival model that all study subjects would experience the failure event of interest eventually if the follow-up time is long enough, some subjects may never experience or not be susceptible to the event. Such subjects are treated as cured and assumed to belong to a cured subgroup in a study population. The research in this dissertation focuses on regression analysis of correlated intervalcensored data with a cured subgroup via different approaches based on different data structures. In the first part of this dissertation, we discuss clustered interval-censored data with a cured subgroup and informative cluster size. To address this, we present a within-cluster resampling method and in the approach, the multiple imputation procedure is applied for estimation of unknown parameters. To assess the performance of the proposed method, a simulation study is conducted and suggests that it works well in practical situations. Also, the method is applied to a set of real data that motivated this study. In the second part of this dissertation, we consider the clustered interval-censored data with a cured subgroup via a non-mixture cure model. We present a maximum likelihood estimation procedure under the semiparametric transformation nonmixture cure model. To estimate the unknown parameters, an expectation maximization (EM) algorithm based on an augmentation of Poisson variable is developed. To assess the performance of the proposed method, a simulation study is conducted and suggests that it works well in practical situations. An application to a study conducted by the National Aeronautics and Space Administration that motivated this study is also provided. In the third part of this dissertation, we investigate the bivariate interval-censored data with a cured subgroup. A sieve maximum likelihood estimation procedure under the semiparametric transformation non-mixture cure model based on Bernstein polynomials is presented. A simulation study is conducted to assess the finite sample performance of the proposed method and suggests that the proposed model works well. Also, a real data application from the study of AIDS Clinical Trial Group 181 is provided

Frailty models

-

Mixture cure model with random effects for the analysis of a multi-center tonsil cancer study

Cure models for clustered survival data have the potential for broad applicability. In this paper, we consider the mixture cure model with random effects and propose several estimation methods based on Gaussian quadrature, rejection sampling, and importance sampling to obtain the maximum likelihood estimates of the model for clustered survival data with a cure fraction. The methods are flexible to accommodate various correlation structures. A simulation study demonstrates that the maximum likelihood estimates of parameters in the model tend to have smaller biases and variances than the estimates obtained from the existing methods. We apply the model to a study of tonsil cancer patients clustered by treatment centers to investigate the effect of covariates on the cure rate and on the failure time distribution of the uncured patients. The maximum likelihood estimates of the parameters demonstrate strong correlation among the failure times of the uncured patients and weak correlation among cure statuses in the same center. Copyright © 2010 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79409/1/4098_ftp.pd

Statistical Modelling of Breastfeeding Data

This thesis addresses some key methodological problems in statistical modelling of breastfeeding data. Meta-analysis techniques were used to analyse aggregated breastfeeding data. Generalised linear mixed model and an extended Cox model were used with time-varying exposures to analyse longitudinal and time-to-event breastfeeding data, respectively. Shared frailty models were applied to correlated breastfeeding duration data controlling for heterogeneity. A novel two-part mixed-effects model was proposed for modelling clustered time-to-event breastfeeding data with clumping at zero

New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel

By 2020, the global health community aims to control and eliminate human helminthiases, including schistosomiasis in selected African countries, principally by preventive chemotherapy (PCT) through mass drug administration (MDA) of anthelminthics. Quantitative monitoring of anthelminthic responses is crucial for promptly detecting changes in efficacy, potentially indicative of emerging drug resistance. Statistical models offer a powerful means to delineate and compare efficacy among individuals, among groups of individuals and among populations.; We illustrate a variety of statistical frameworks that offer different levels of inference by analysing data from nine previous studies on egg counts collected from African children before and after administration of praziquantel.; We quantify responses to praziquantel as egg reduction rates (ERRs), using different frameworks to estimate ERRs among population strata, as average responses, and within strata, as individual responses. We compare our model-based average ERRs to corresponding model-free estimates, using as reference the World Health Organization (WHO) 90 % threshold of optimal efficacy. We estimate distributions of individual responses and summarize the variation among these responses as the fraction of ERRs falling below the WHO threshold.; Generic models for evaluating responses to anthelminthics deepen our understanding of variation among populations, sub-populations and individuals. We discuss the future application of statistical modelling approaches for monitoring and evaluation of PCT programmes targeting human helminthiases in the context of the WHO 2020 control and elimination goals

A Transformation Class for Spatio-temporal Survival Data with a Cure Fraction

We propose a hierarchical Bayesian methodology to model spatially or spatio-temporal clustered survival data with possibility of cure. A flexible continuous transformation class of survival curves indexed by a single parameter is used. This transformation model is a larger class of models containing two special cases of the well-known existing models: the proportional hazard and the proportional odds models. The survival curve is modeled as a function of a baseline cumulative distribution function, cure rates, and spatio-temporal frailties. The cure rates are modeled through a covariate link specification and the spatial frailties are specified using a conditionally autoregressive model with time-varying parameters resulting in a spatio-temporal formulation. The likelihood function is formulated assuming that the single parameter controlling the transformation is unknown and full conditional distributions are derived. A model with a non-parametric baseline cumulative distribution function is implemented and a Markov chain Monte Carlo algorithm is specified to obtain the usual posterior estimates, smoothed by regional level maps of spatio-temporal frailties and cure rates. Finally, we apply our methodology to melanoma cancer survival times for patients diagnosed in the state of New Jersey between 2000 and 2007, and with follow-up time until 2007

A dynamic Mover–Stayer model for recurrent event processes

The final publication is available at Springer via http://dx.doi.org/10.1007/s10985-013-9271-7In studies of affective disorder, individuals are often observed to experience recurrent symptomatic exacerbations warranting hospitalization. Interest may lie in modeling the occurrence of such exacerbations over time and identifying associated risk factors. In some patients, recurrent exacerbations are temporally clustered following disease onset, but cease to occur after a period of time.We develop a dynamic Mover-Stayer model in which a canonical binary variable associated with each event indicates whether the underlying disease has resolved. An individual whose disease process has not resolved will experience events following a standard point process model governed by a latent intensity. When the disease process resolves, the complete data intensity becomes zero and no further event will occur. An expectation- maximization algorithm is described for parametric and semiparametric model fitting based on a discrete time dynamic Mover-Stayer model and a latent intensity-based model of the underlying point process.RJC: Natural Sciences and Engineering Research Council of Canada (RGPIN 155849); Canadian Institutes for Health Research (FRN 13887); Canada Research Chair (Tier 1) – CIHR funded (950-226626) HS: Grant from the Division of High Impact Clinical Trials of the Ontario Institute for Cancer Researc

Maternal Employment and Childhood Obesity: A Search for Mechanisms in Time Use Data

Recent research has found that maternal employment is associated with an increased risk of childhood obesity. This paper explores mechanisms for that correlation. We estimate models of instrumental variables using a unique dataset, the American Time Use Survey, that measure the effect of maternal employment on the mother’s allocation of time to activities related to child diet and physical activity. We find that employed women spend significantly less time cooking, eating with their children, and playing with their children, and are more likely to purchase prepared foods. We find suggestive evidence that these decreases in time are only partly offset by husbands and partners. These findings offer plausible mechanisms for the association of maternal employment with childhood obesity.