Abstract

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.

Highlights

  • In case-control studies most algorithms allow the controls to be sampled several times, which is not always optimal

  • We investigated the association between the prescription of oral antibiotics and colorectal cancer

  • To increase balance in the population, we introduced the Comorbidity Index (CI) variable, which is the sum of chronic diseases as a means to have comparable units for drawing valid associations

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Summary

Introduction

In case-control studies most algorithms allow the controls to be sampled several times, which is not always optimal. If many controls are available and adjustment for several covariates is necessary, matching without replacement might increase statistical efficiency. The aim was twofold, firstly to create a method that accommodates the option that a control is not resampled, and second, to display several scenarios that identify changes of Odds Ratios (ORs) while increasing the balance of the matched sample. Observational studies might complement RCTs in hypothesis generation or even establishing questions for future RCTs [2, 3]. Due to non-randomization, they are more prone to bias, which can be addressed through careful study design and appropriate statistical analysis [4]. Observational studies include, among others, the cohort and the case-control studies [3].

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