A Combined Criterion for Dose Optimisation in Early Phase Clinical Trials

Abstract

A combined criterion is introduced for dose optimisation in seamless phase I/II clinical trials. The design considers efficacy and toxicity as endpoints. The criterion is based on the probability of a successful outcome and on the determinant of the Fisher information matrix for estimation of the dose-response parameters.? Starting with the lowest dose, the design selects that dose for each subsequent cohort that maximises the defined criterion. The methodology is illustrated with a dose-response model that assumes trinomial responses. The aim is to investigate whether any bridge is possible between best intention and D-optimum designs. Simulation studies show that the method is capable of identifying the optimal dose accurately without exposing many patients to toxic doses. (The talk is based on joint work with Iftakhar Alam at the University of Dhaka and Barbara Bogacka at Queen Mary, University of London.)