贝叶斯期中分析与III期随机试验的效率

Bayesian interim analysis and efficiency of phase III randomized trials.

作者信息

Sherry Alexander D, Msaouel Pavlos, Miller Avital M, Lin Timothy A, Kupferman Gabrielle S, Abi Jaoude Joseph, Kouzy Ramez, El-Alam Molly B, Patel Roshal, Koong Alex, Lin Christine, Meirson Tomer, McCaw Zachary R, Ludmir Ethan B

机构信息

Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.

出版信息

Br J Cancer. 2025 Aug 11. doi: 10.1038/s41416-025-03156-5.

DOI:10.1038/s41416-025-03156-5

PMID:40789942

Abstract

BACKGROUND

Improving efficiency of phase III trials is paramount for reducing costs, hastening approvals, and mitigating exposure to disadvantageous randomizations. Compared to standard frequentist interim analysis, Bayesian early stopping rules may improve efficiency by the flexibility of differential priors for efficacy and futility coupled with evaluation of clinically meaningful effect sizes.

METHODS

Individual patient-level data from 184,752 participants across 230 randomized two-arm parallel oncology phase III trials were manually reconstructed from primary endpoint Kaplan-Meier curves. Accrual dynamics, but not patient outcomes, were randomly varied. Bayesian Cohen's κ assessed agreement between the original analysis and the Bayesian interim analysis.

RESULTS

Trial-level early closure was recommended based on the Bayesian interim analysis for 82 trials (36%), including 62 trials which had performed frequentist interim analysis and 33 which were already closed early by the frequentist interim analysis. Bayesian early stopping rules were 96% sensitive for detecting trials with a primary endpoint difference, and there was a high level of agreement in overall trial interpretation (κ, 0.95). Moreover, Bayesian interim analysis was associated with reduced enrollment.

CONCLUSIONS

Bayesian interim analyses seem to improve trial efficiency by reducing enrollment requirements without compromising interpretation.

摘要

背景

提高III期试验的效率对于降低成本、加快审批以及减少不利随机化的影响至关重要。与标准的频率学派中期分析相比，贝叶斯早期终止规则可以通过灵活设定疗效和无效性的差异先验以及评估具有临床意义的效应大小来提高效率。

方法

从230项随机双臂平行肿瘤学III期试验的184,752名参与者的个体患者水平数据中，根据主要终点的Kaplan-Meier曲线手动重建。累积动态情况随机变化，但患者结局不变。贝叶斯科恩κ系数评估原始分析与贝叶斯中期分析之间的一致性。

结果

基于贝叶斯中期分析，建议对82项试验（36%）进行试验水平的早期关闭，其中包括62项进行了频率学派中期分析的试验和33项已通过频率学派中期分析提前关闭的试验。贝叶斯早期终止规则对检测具有主要终点差异的试验的敏感性为96%，并且在整体试验解读方面具有高度一致性（κ系数为0.95）。此外，贝叶斯中期分析与减少入组人数相关。