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Aydemir, Sibel and Hornsteiner, U. (1997): Analyse zeitveraenderlicher Kovariablen und rekurrenter Ereignisse am Beispiel einer Studie zur prophylaktischen Behandlung von Oesophagusvarizen. Collaborative Research Center 386, Discussion Paper 81 [PDF, 387kB]


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.

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