A new function for drug combination dose finding trials

Abstract

Abstract Combination drugs play an essential role in treating cancers. The challenging part of the combination drugs are to specify the dose-toxicity ordering, which means the sequences of dose escalation and de-escalation in process of dose findings should be pre-determined. In the paper, we extend a novel function of the continual reassessment method based on the combination of the normal distribution for drug-combination dose-finding trials and systematically evaluate its performance using a template of four performance measures EARS (Efficiency, Accuracy, Reliability, Selection). Dose escalation and deescalation rules are based on the nearest neighborhood continual reassessment method for a combination drug, and we specify all possible dose-toxicity orderings in the trial. Simulation demonstrates that the new design is efficient, accurate and reasonably reliable.