Limitations of the BOIN Design

Music City Center 

The Bayesian Optimal Interval (BOIN) design has recently become popular in oncology dose-finding trials (Liu, 2015). The local BOIN design has successfully passed the FDA's Fit-for-Purpose (FFP) evaluation, receiving a determination letter certifying its FFP status under a non-informative prior. However, this paper highlights several potential limitations of the local BOIN design. Notably, the criteria for escalation, retention, and de-escalation are independent of sample size, which contradicts both clinical and statistical reasoning. Furthermore, the design is based on questionable hypotheses and the minimization of the sum of Type I and Type II error rates. The Type I error rate can fluctuate between 0 and 1, with a rate of 1 leading to the abandonment of the current dose regardless of trial outcomes. It is essential to consider these limitations when implementing the BOIN design in clinical trials.

drug label

LOCF

MMRM

MMRM

Trajectory of Mean (Median) and Observation Rate (TMOR) plot

go/No-go 

Biopharmaceutical Section