A curve-free Bayesian decision-theoretic design for two-agent Phase I trials

作者：Lee Bee L^*; Fan Shenghua K; Lu Ying

来源：Journal of Biopharmaceutical Statistics, 2017, 27(1): 34-43.

DOI：10.1080/10543406.2016.1148713

• Dose allocation
• maximum tolerated dose
• Phase I trial
• stopping rules
• two-agent trials
• utility function

Although Bayesian statistical methods are gaining attention in the medical community, as they provide a natural framework for incorporating prior information, the complexity of these methods limited their adoptions in clinical trials. This article proposes a Bayesian design for two-agent Phase I trials that is relatively easy for clinicians to understand and implement, yet performs comparably to more complex designs, so that it is more likely to be adopted in actual trials. In order to reduce model complexity and computational burden, we choose a working model with conjugate priors so that the posterior distributions have analytical expressions. Furthermore, we provide a simple strategy to facilitate the specification of priors based on the toxicity information accrued from single-agent Phase I trials. The proposed method should be useful in terms of the ease of implementation and the savings in sample size without sacrificing performance. Moreover, the conservativeness of the dose-finding algorithm renders it a relatively safe method.

• 出版日期2017