Adaptive seamless phase II/III design with sequential estimation-adjusted urn model

Abstract

Clinical trials are an essential component of the drug development process, providing crucial data on the efficacy and safety of new treatments. However, traditional clinical trial designs can be inefficient and ineffective, leading to increased costs and a higher risk of failure. The FDA Oncology Center of Excellence (OCE) has recently initiated Project Optimus to reform the dose selection paradigm for oncology treatments. We propose the adaptive seamless phase II/III clinical trial designs (ASD) with the sequential estimation-adjusted urn (SEU) model for randomization to achieve efficient and ethical objectives. However, the combination of ASD and SEU poses a challenge in controlling the type I error rate: ASD exerts a dual influence of multiplicity and selection; all the responses and treatment assignments are not independent due to SEU. In this paper, we investigated how to overcome these difficulties, utilize the two adaptive approaches’ advantages, and control the type I error rate. We provide a theoretical foundation for this procedure, and numerical studies demonstrate that our methods can assign more people to better treatments, leading to fewer failures while still controlling the type I error rate and preserving power.

Keywords:

• Clinical trials
• Ethics
• Response adaptive randomization
• Type I error

Acknowledgements

This publication was neither originated nor managed by AbbVie, and it does not communicate results of AbbVie-sponsored Scientific Research. Thus, it is not in scope of the AbbVie Publication Procedure (PUB-100).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was partly supported by grant DMS-2014951 (Dr. Hongjian Zhu) from the National Science Foundation (USA) and Weatherhead Foundation (Dr. Dejian Lai).