A hybrid design for Phase I clinical trials

Abstract Background: How to determine the maximum tolerated dose (MTD) is the primary objective in phase I clinical trial. The study indicates that the trial would fail, largely because a suboptimal dose is recommended to the further stage. The overly toxic dose assigned to patients during the treatment could lead to irreversible damage and even death, as a result, the safety of the design has been frequently emphasized. Methods: We propose a novel hybrid design that incorporates the CRM into the Keyboard design. Results: The hybrid design has superiorities in safety control and accuracy of recommendation over the existing designs. Conclusion: The hybrid design maximizes the merits and minimizes the limitations. In other words, the proposed the method possesses these two advantages, the overdose control and full use of information, meanwhile, the aggressive dose transition of the CRM has been avoided.