Frailty models adjust for between-cluster variability in survival data by
including a cluster-specific random factor, the frailty term, in the Cox model. The
frailty term is assumed to be constant over time. This assumption is questionable in
some particular settings, e.g., in cancer clinical trials on chronic myeloid leukaemia.
We therefore relax the time-constant heterogeneity assumption and consider frailty
models with a time-varying frailty term. Instead of working with hazard models, we
rather model the log cumulative hazard function, making use of the mixed model
framework, and introduce a time-varying random effect at that level. Simulations
demonstrate that the proposed method has acceptable size and power to detect time-
dependent clustering. The method is applied to data from a large-scale multicentre
clinical trial in patients with chronic myeloid leukaemia.

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• Testing for decreasing heterogeneity in a new time-varying frailty model