Joint modelling of longitudinal and time-to-event data applied to group sequential clinical trials

Abstract: Often in Phase 3 clinical trials measuring a long-term time-to-event endpoint, such as overall survival or progression-free survival, investigators also collect repeated measures on biomarkers which may be predictive of the primary endpoint. Although these data may not be leveraged directly to support early stopping decisions, can we make greater use of these data to increase efficiency and improve interim decision making? We present a joint model for longitudinal and time-to-event data and a method which establishes the distribution of successive estimates of parameters in the joint model across interim analyses. With this in place, we can use the estimates to define both efficacy and futility stopping rules. Using simulation, we evaluate the benefits of incorporating biomarker information and the affects on interim decision making.