Analyse zeitveraenderlicher Kovariablen und rekurrenter Ereignisse am Beispiel einer Studie zur prophylaktischen Behandlung von Oesophagusvarizen

To assess the effect of prophylactic sclerotherapy on variceal
hemorrhage and survival of patients with liver cirrhosis and
esophageal varices, a randomized study had been carried out. We
analysed the data from different points of view. The time-dependent
Cox model and the linear counting process of Aalen are applied
allowing for the time-dependent covariate ``variceal bleeding`` --
that switches up to three times -- in a multivariate analysis of
the remaining life time. A model for the times to and between the
recurrent events of bleeding including unobserved heterogeneity is
estimated by a distribution-free and by a parametric method where
the latter also admits time-dependent covariates such as repeated
measurements of laboratory data. We find that high age, high
Child-Pugh score and especially the first occurence of variceal
bleeding have a statistically significant negative effect on
survival whereas patients with fundic varices and/or alcoholic
cirrhosis have a significant higher risk of bleeding. In both
analyses, inclusion of time-dependent covariates does not change
the estimation substantially. In particular, prophylactic
sclerotherapy is not shown to reduce the risk of bleeding nor dying
significantly.