This paper according to Dr. Andrew G. Chapple, of the Louisiana State University Health Sciences Center School of Public Health, proposes a new design paradigm, motivated by the possibility that the optimal phase I‐II dose may not maximize mean survival time with A.
Dr. Chapple and Dr. Thall propose a hybridized design, which they call phase I‐II/III, that combines phase I‐II and phase III by allowing the chosen optimal phase I‐II dose of A to be re‐optimized based on survival time data from phase I‐II patients and the first portion of phase III. The phase I‐II/III design uses adaptive randomization in phase I‐II and relies on a mixture model for the survival time distribution as a function of efficacy, toxicity, and dose. A simulation study is presented to evaluate the phase I‐II/III design and compare it to the usual approach that does not re‐optimize the dose of A in phase III.
