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03 June 2019

Consider a Phase 3 clinical trial where the primary endpoint is overall survival. The investigators wish to define a group sequential stopping rule which allows for the early stopping for efficacy, but there is a particular interest in early stopping for futility. Suppose that longitudinal data are observed on a biomarker which is assumed to be predictive of survival, and we wish to use this biomarker information to inform early stopping decisions. We shall present a joint model for survival and longitudinal data and a method which establishes the distribution of successive estimates of parameters in the joint model across interim analyses.  Then, we are equipped to use the estimates to define a futility stopping rule. With the methodology in place, by simulation we can assess the potential benefits of including biomarker information, how this affects interim decisions and ultimately alters the trial.

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