Balancing the effective sample size in prior across different doses in the curve-free Bayesian decision-theoretic design for dose-finding trials
Jiayi Xu et al.
What the paper says
The primary goal of dose allocation in phase I trials is to minimize patient exposure to subtherapeutic or excessively toxic doses, while accurately recommending a phase II dose that is as close as possible to the maximum tolerated dose (MTD). Fan introduced a curve-free Bayesian decision-theoretic design (CFBD), which leverages the assumption of a monotonic dose-toxicity relationship without directly modeling dose-toxicity curves. This approach has also been extended to drug combinations for determining the MTD. Although CFBD has demonstrated improved trial efficiency by using fewer patients while maintaining high accuracy in identifying the MTD, it may artificially inflate the effective sample sizes for the updated prior distributions, particularly at the lowest and highest dose levels. This can lead to either overshooting or undershooting the target dose. In this paper, we propose a modification to CFBD's prior distribution updates that balances effective sample sizes across different doses. Simulation results show that with the modified prior specification, CFBD achieves a more focused-dose allocation at the MTD and offers more precise-dose recommendations with fewer patients on average. It also demonstrates robustness to other well-known dose finding designs in literature.
Evidence weight
Balanced mode · F 0.40 / M 0.15 / V 0.05 / R 0.40
| F · citation impact | 0.50 × 0.4 = 0.20 |
| M · momentum | 0.50 × 0.15 = 0.07 |
| V · venue signal | 0.50 × 0.05 = 0.03 |
| R · text relevance † | 0.50 × 0.4 = 0.20 |
† Text relevance is estimated at 0.50 on the detail page — for your query’s actual relevance score, open this paper from a search result.