Title: Optimal dose-finding for drug combinations
Authors: Renata Eirini Tsirpitzi - Stockholm University (Sweden) [presenting]
Frank Miller - Stockholm University (Sweden)
Abstract: A combination of drugs is frequently done in clinical praxis. Therefore, the effect of a combination treatment should be investigated in clinical studies before. We explore the optimal combination and the optimal doses by improving the efficacy when two drugs are simultaneously present. We consider an efficacy Emax model for combining two drugs by including an interaction parameter. There are three possible interactions between the two drugs. When the interaction parameter is equal to 0, then there is no interaction and is called additivity. If the parameter is positive, then we have synergy between the two drugs. When the deviation of the interaction term from 0 is negative, then the interaction is considered antagonism. The optimality criterion used is the D-optimality and the results were obtained by applying our own developed algorithm which is based on the Fedorov algorithm. The results indicate that the number of doses, the doses, and their weights depend strongly on the model parameters.