Discussion of 'A Hybrid Phase I-II/III Clinical Trial Design Allowing Dose Re-Optimization in Phase III' by Andrew G. Chapple and Peter F. Thall

The document reviews a novel hybrid phase I-II/III clinical trial design by Chapple and Thall, which is particularly aimed at cancer drug development and allows for dose re-optimization during phase III based on safety, efficacy, and patient survival. Zhou and Ji, the authors of the discussion, praise the design but highlight challenges such as timely efficacy assessment and the assumption of a consistent study population throughout the trial phases. They also consider the implications of adaptive randomization and the trade-offs involved in re-optimizing the dose during phase III. They conclude that while the design holds promise, further empirical evidence from real-world trials is necessary to evaluate its broad applicability and possible improvements.