Introduction of accelerated BOIN design and facilitation of its application

TL;DR

This paper introduces an accelerated BOIN design for phase I clinical trials that reduces study duration and sample size, making it comparable to the traditional 3+3 design while maintaining accuracy.

Contribution

The paper presents a novel accelerated BOIN design with stopping criteria and cohort size adjustments to speed up dose escalation trials.

Findings

Accelerated BOIN reduces study duration by 14.8 months.

It decreases sample size by 9.22 months on average.

Performance is comparable to standard BOIN with improved efficiency.

Abstract

Purpose: During discussions at the Data Science Roundtable meeting in Japan, there were instances where the adoption of the BOIN design was declined, attributed to the extension of study duration and increased sample size in comparison to the 3+3 design. We introduce an accelerated BOIN design aimed at completing a clinical phase I trial at a pace comparable to the 3+3 design. Additionally, we introduce how we could have applied the BOIN design within our company, which predominantly utilized the 3+3 design for most of its clinical oncology dose escalation trials. Methods: The accelerated BOIN design is adaptable by using efficiently designated stopping criterion for the existing BOIN framework. Our approach is to terminate the dose escalation study if the number of evaluable patients treated at the current dose reaches 6 and the decision is to stay at the current dose for the next cohort of patients. In addition, for lower dosage levels, considering a cohort size smaller than 3 may be feasible when there are no safety concerns from non-clinical studies. We demonstrate the accelerated BOIN design using a case study and subsequently evaluate the performance of our proposed design through a simulation study. Results: In the simulation study, the average difference in the percentage of correct MTD selection between the accelerated BOIN design and the standard BOIN design was -2.43%, the average study duration and the average sample size of the accelerated BOIN design was reduced by 14.8 months and 9.22 months, respectively, compared with the standard BOIN design. Conclusion: We conclude that our proposed accelerated BOIN design not only provides superior operating characteristics but also enables the study to be completed as fast as the 3+3 design.