Eliminating a sparse data problem in nonparametric bivariate survival analysis with an application to women's age at first marriage and age at first birth

A new solution is proposed for a sparse data problem arising in nonparametric estimation of a bivariate survival function. Prior information, if available, can be used to obtain initial values for the EM algorithm. Initial values will completely determine estimates of portions of the distribution which are not identifiable from the data, while having a minimal effect on estimates of portions of the distribution for which the data provide sufficient information. Methods are applied to the distribution of women's age at first marriage and age at birth of first child, using data from the Current Population Surveys of 1975 and 1986.     

Regression analysis of panel count data with covariate-dependent observation and censoring times

Panel count data often occur in a long-term study where the primary end point is the time to a specific event and each subject may experience multiple recurrences of this event. Furthermore, suppose that it is not feasible to keep subjects under observation continuously and the numbers of recurrences for each subject are only recorded at several distinct time points over the study period. Moreover, the set of observation times may vary from subject to subject. In this paper, regression methods, which are derived under simple semiparametric models, are proposed for the analysis of such longitudinal count data. Especially, we consider the situation when both observation and censoring times may depend on covariates. The new procedures are illustrated with data from a well-known cancer study.     

Non-ignorable missing covariate data in survival analysis: a case-study of an International Breast Cancer Study Group trial

Summary.  Non-ignorable missing data, a serious problem in both clinical trials and observational studies, can lead to biased inferences. Quality-of-life measures have become increasingly popular in clinical trials. However, these measures are often incompletely observed, and investigators may suspect that missing quality-of-life data are likely to be non-ignorable. Although several recent references have addressed missing covariates in survival analysis, they all required the assumption that missingness is at random or that all covariates are discrete. We present a method for estimating the parameters in the Cox proportional hazards model when missing covariates may be non-ignorable and continuous or discrete. Our method is useful in reducing the bias and improving efficiency in the presence of missing data. The methodology clearly specifies assumptions about the missing data mechanism and, through sensitivity analysis, helps investigators to understand the potential effect of missing data on study results.     

Marriage or cohabitation: a competing risks analysis of first-partnership formation among the 1958 British birth cohort

A discrete time competing risks hazards model is used to analyse entry into first partnership among men and women born in Britain in 1958. Using a life-course approach we identify family background and current life experiences which affect the timing and type of first-partnership formation. Education is a key factor influencing the age of entry into first partnership and whether or not the respondent will experience pregnancy before forming the partnership. Religiosity, experience of parental separation and the geographical region of residence are more important in affecting the decision to cohabit rather than to marry directly. The analyses highlight the importance of transitions in other domains such as leaving the parental home in encouraging cohabitation.     

Non‐inferiority and networks: inferring efficacy from a web of data

In the absence of placebo‐controlled trials, the efficacy of a test treatment can be alternatively examined by showing its non‐inferiority to an active control; that is, the test treatment is not worse than the active control by a pre‐specified margin. The margin is based on the effect of the active control over placebo in historical studies. In other words, the non‐inferiority setup involves a network of direct and indirect comparisons between test treatment, active controls, and placebo. Given this framework, we consider a Bayesian network meta‐analysis that models the uncertainty and heterogeneity of the historical trials into the non‐inferiority trial in a data‐driven manner through the use of the Dirichlet process and power priors. Depending on whether placebo was present in the historical trials, two cases of non‐inferiority testing are discussed that are analogs of the synthesis and fixed‐margin approach. In each of these cases, the model provides a more reliable estimate of the control given its effect in other trials in the network, and, in the case where placebo was only present in the historical trials, the model can predict the effect of the test treatment over placebo as if placebo had been present in the non‐inferiority trial. It can further answer other questions of interest, such as comparative effectiveness of the test treatment among its comparators. More importantly, the model provides an opportunity for disproportionate randomization or the use of small sample sizes by allowing borrowing of information from a network of trials to draw explicit conclusions on non‐inferiority. Copyright © 2015 John Wiley & Sons, Ltd.     

Imputing missing quality of life data as covariate in survival analysis of the International Breast Cancer Study Group Trials VI and VII

Quality of life (QoL) was an important endpoint in the adjuvant breast cancer trials International Breast Cancer Study Group (IBCSG) Trial VI and VII. Here, QoL was considered as a time-dependent effect. The hypothesis explored is that poorer QoL throughout the trial is associated with poorer disease-free survival (DFS) and vice-versa. Potential bias in the parameter estimates is an important concern associated with missing observations. Standard simple and multiple imputation methods were applied to missing QoL assessments before analysis in a time-dependent Cox model. There was no evidence that the patient's QoL is related to the patient's DFS.     

Performance of standard imputation methods for missing quality of life data as covariate in survival analysis based on simulations from the International Breast Cancer Study Group Trials VI and VII*

Abstract

Imputation methods for missing data on a time-dependent variable within time-dependent Cox models are investigated in a simulation study. Quality of life (QoL) assessments were removed from the complete simulated datasets, which have a positive relationship between QoL and disease-free survival (DFS) and delayed chemotherapy and DFS, by missing at random and missing not at random (MNAR) mechanisms. Standard imputation methods were applied before analysis. Method performance was influenced by missing data mechanism, with one exception for simple imputation. The greatest bias occurred under MNAR and large effect sizes. It is important to carefully investigate the missing data mechanism.     

Survival and lifetime data analysis with a flexible class of distributions

We introduce a general class of continuous univariate distributions with positive support obtained by transforming the class of two-piece distributions. We show that this class of distributions is very flexible, easy to implement, and contains members that can capture different tail behaviours and shapes, producing also a variety of hazard functions. The proposed distributions represent a flexible alternative to the classical choices such as the log-normal, Gamma, and Weibull distributions. We investigate empirically the inferential properties of the proposed models through an extensive simulation study. We present some applications using real data in the contexts of time-to-event and accelerated failure time models. In the second kind of applications, we explore the use of these models in the estimation of the distribution of the individual remaining life.     

The transition from university to work: a multilevel approach to the analysis of the time to obtain the first job

The aim of the paper is to characterize the factors that determine the transition from university to work as well as to evaluate the effectiveness of universities and course programmes with respect to the labour market outcomes of their graduates. The study is focused on the analysis of the time to obtain the first job, taking into account the graduates' characteristics and the effects pertaining to course programmes and universities. For this a three-level discrete time survival model is used, where the logit of the hazard—conditionally on the random effects at course programme and university level—is a linear function of the covariates. The analysis is accomplished by using a large data set from a survey on job opportunities for the 1992 Italian graduates.     

A comparison of procedures to correct for base-line differences in the analysis of continuous longitudinal data: a case-study

Summary.  The main advantage of longitudinal studies is that they can distinguish changes over time within individuals (longitudinal effects) from differences between subjects at the start of the study (base-line characteristics; cross-sectional effects). Often, especially in observational studies, subjects are very heterogeneous at base-line, and one may want to correct for this, when doing inferences for the longitudinal trends. Three procedures for base-line correction are compared in the context of linear mixed models for continuous longitudinal data. All procedures are illustrated extensively by using data from an experiment which aimed at studying the relationship between the post-operative evolution of the functional status of elderly hip fracture patients and their preoperative neurocognitive status.     

Case study in data analysis: Variables related to codling moth abundance and the efficacy of the Okanagan Sterile Insect Release Program

The authors consider the effect of orchard attributes and landscape in a heterogeneous area on the efficacy of a control program for the codling moth in apple orchards in British Columbia. The context is first presented, along with a set of questions of importance to the Okanagan Valley Sterile Insect Release program. Two groups of analysts then address a number of these issues using methods for spatial‐temporal data including counts, proportions and Bernoulli variables. The models are then compared and the relevance of the results to this operational program is discussed.     

R package for analysis of data with mixed measurement error and misclassification in covariates: augSIMEX

Measurement error and misclassification arise commonly in various data collection processes. It is well-known that ignoring these features in the data analysis usually leads to biased inference. With the generalized linear model setting, Yi et al. [Functional and structural methods with mixed measurement error and misclassification in covariates. J Am Stat Assoc. 2015;110:681–696] developed inference methods to adjust for the effects of measurement error in continuous covariates and misclassification in discrete covariates simultaneously for the scenario where validation data are available. The augmented simulation-extrapolation (SIMEX) approach they developed generalizes the usual SIMEX method which is only applicable to handle continuous error-prone covariates. To implement this method, we develop an R package, augSIMEX, for public use. Simulation studies are conducted to illustrate the use of the algorithm. This package is available at CRAN.     

Analysis of longitudinal data with drop-out: objectives, assumptions and a proposal

Summary. The problem of analysing longitudinal data that are complicated by possibly informative drop-out has received considerable attention in the statistical literature. Most researchers have concentrated on either methodology or application, but we begin this paper by arguing that more attention could be given to study objectives and to the relevant targets for inference. Next we summarize a variety of approaches that have been suggested for dealing with drop-out. A long-standing concern in this subject area is that all methods require untestable assumptions. We discuss circumstances in which we are willing to make such assumptions and we propose a new and computationally efficient modelling and analysis procedure for these situations. We assume a dynamic linear model for the expected increments of a constructed variable, under which subject-specific random effects follow a martingale process in the absence of drop-out. Informal diagnostic procedures to assess the tenability of the assumption are proposed. The paper is completed by simulations and a comparison of our method and several alternatives in the analysis of data from a trial into the treatment of schizophrenia, in which approximately 50% of recruited subjects dropped out before the final scheduled measurement time.     

Joint modelling of longitudinal response and time-to-event data using conditional distributions: a Bayesian perspective

Over the last 20 or more years a lot of clinical applications and methodological development in the area of joint models of longitudinal and time-to-event outcomes have come up. In these studies, patients are followed until an event, such as death, occurs. In most of the work, using subject-specific random-effects as frailty, the dependency of these two processes has been established. In this article, we propose a new joint model that consists of a linear mixed-effects model for longitudinal data and an accelerated failure time model for the time-to-event data. These two sub-models are linked via a latent random process. This model will capture the dependency of the time-to-event on the longitudinal measurements more directly. Using standard priors, a Bayesian method has been developed for estimation. All computations are implemented using OpenBUGS. Our proposed method is evaluated by a simulation study, which compares the conditional model with a joint model with local independence by way of calibration. Data on Duchenne muscular dystrophy (DMD) syndrome and a set of data in AIDS patients have been analysed.     

Sensitivity analysis of longitudinal count responses: a local influence approach and application to medical data

Longitudinal count responses are often analyzed with a Poisson mixed model. However, under overdispersion, these responses are better described by a negative binomial mixed model. Estimators of the corresponding parameters are usually obtained by the maximum likelihood method. To investigate the stability of these maximum likelihood estimators, we propose a methodology of sensitivity analysis using local influence. As count responses are discrete, we are unable to perturb them with the standard scheme used in local influence. Then, we consider an appropriate perturbation for the means of these responses. The proposed methodology is useful in different applications, but particularly when medical data are analyzed, because the removal of influential cases can change the statistical results and then the medical decision. We study the performance of the methodology by using Monte Carlo simulation and applied it to real medical data related to epilepsy and headache. All of these numerical studies show the good performance and potential of the proposed methodology.     

Stratified analysis of correlated binary outcome data: a comparison of model dependent and robust tests of significance

Model dependent and robust test statistics constructed using a generalized estimating equations extension of logistic regression applicable to the analysis of correlated binary outcome data are shown to have relatively simple algebraic expressions in stratified analyses where all variables are measured at the cluster level These expressions are used to demonstrate the close relationship to standard procedures which assume that subjects responses are independent, to prove that the asymptotic validity of model dependent test statistics is assured if the average correlation between cluster members is constant, and that this assumption can be relaxed when there are the same number of subjects in each cluster.     

Bayesian analysis of contingency tables: a simulation and graphics-based approach

In this paper we present a simulation and graphics-based model checking and model comparison methodology for the Bayesian analysis of contingency tables. We illustrate the approach by testing the hypotheses of independence and symmetry on complete and incomplete simulated tables.     

The First Exit Time Theory Applied to Life Table Data: The Health State Function of a Population and Other Characteristics

In this article, we summarize the main parts of the first exit time theory developed in connection to the life table data and the resulting theoretical and applied issues. New tools arise from the development of this theory and especially the Health State Function and some important characteristics of this function.

We provide both simple and complex models and propose a methodology for reconstructing the health state function from the provided first exit time density distribution (for the appropriate computer program, see http://www.cmsim.net). In the simpler case, this theory is applied for the reconstruction of the so-called Inverse-Gaussian function.     

Joint analysis of occurrence and time to stability after entrance into the Italian labour market: an approach based on a Bayesian cure model with structured stochastic search variable selection

Precarious employment is a serious social problem, especially in those countries, such as Italy, where there are limited benefits from social security. We investigate this phenomenon by analysing the initial part of the career of employees starting with unstable contracts for a panel of Italian workers. Our aim is to estimate the probability of getting a stable job and to detect factors influencing both this probability and the duration of precariousness. To answer these questions, we use an ad hoc mixture cure rate model in a Bayesian framework.