Practical recommendations for implementing a Bayesian adaptive phase I design during a pandemic

Abstract

Abstract Background Modern designs for dose-finding studies (e.g., model-based designs such as continual reassessment method) have been shown to substantially improve the ability to determine a suitable dose for efficacy testing when compared to traditional designs such as the 3 + 3 design. However, implementing such designs requires time and specialist knowledge. Methods We present a practical approach to developing a model-based design to help support uptake of these methods; in particular, we lay out how to derive the necessary parameters and who should input, and when, to these decisions. Designing a model-based, dose-finding trial is demonstrated using a treatment within the AGILE platform trial, a phase I/II adaptive design for novel COVID-19 treatments. Results We present discussion of the practical delivery of AGILE, covering what information was found to support principled decision making by the Safety Review Committee, and what could be contained within a statistical analysis plan. We also discuss additional challenges we encountered in the study and discuss more generally what (unplanned) adaptations may be acceptable (or not) in studies using model-based designs. Conclusions This example demonstrates both how to design and deliver an adaptive dose-finding trial in order to support uptake of these methods.