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

Published version
Peer-reviewed

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Authors

Ewings, Sean 
Saunders, Geoff 
Mozgunov, Pavel 

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.

Description

Keywords

Research, Bayesian, Phase I, Adaptive design, Dose escalation

Journal Title

BMC Med Res Methodol

Conference Name

Journal ISSN

1471-2288
1471-2288

Volume Title

22

Publisher

Springer Science and Business Media LLC