Dose Finding Studies for Therapies with Late-Onset Safety and Efficacy Outcomes

Abstract: In Phase I/II dose-finding trials, the objective is to find the Optimal Biological Dose (OBD), a dose that is both safe and efficacious that maximises some optimality criterion based on safety and efficacy. This is further complicated when the investigated treatment consists of multiple cycles of therapy, and both toxicity and efficacy outcomes may occur at any point throughout the follow up of multiple cycles. In this work we present the Joint TITE-CRM, a model-based design for late onset toxicities and efficacies based on the well-known TITE-CRM. It is found to be superior to both currently available alternative designs that account for late onset bivariate outcomes; a model-assisted method and a bivariate survival design, as well as being both intuitive and computationally feasible.