BOIN: a novel Bayesian design platform to accelerate early phase brain tumor clinical trials.
BOIN: a novel Bayesian design platform to accelerate early phase brain tumor clinical trials.
复制标题
BOIN：一种新颖的贝叶斯设计平台，可加速早期脑肿瘤临床试验。
DOI：
10.1093/nop/npab035
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发表时间：
2021
影响因子：
2.7
通讯作者：
Gilbert,MarkR
中科院分区：
文献类型：
--
作者：
Yuan,Ying;Wu,Jing;Gilbert,MarkR
尽管经过数十年的广泛研究，原发性脑肿瘤的有效治疗进展仍落后于其他癌症，这主要是由于脑肿瘤的独特挑战（例如，血脑屏障和高度异质性）限制了许多治疗药物的递送和疗效。解决这一问题的一种方法是采用新颖的试验设计，在早期试验中更好地优化治疗方案（如剂量和时间表），以提高随后的III期试验的成功率。本文的目的是介绍贝叶斯最优间隔（BOIN）设计作为设计各种早期脑肿瘤试验的新平台，包括单药和联合方案试验，迟发性毒性试验，以及基于毒性和疗效寻找最佳生物剂量（OBD）的试验。与许多新的贝叶斯自适应设计不同，这些设计很难被临床研究者理解和复杂地实施，BOIN设计是自解释的，用户友好的，但比传统设计产生更强大和强大的操作特性。我们使用脑肿瘤I期临床试验来说明BOIN设计，并提供软件（可在www.trialdesign.org免费获得）以促进BOIN设计的应用。
Despite decades of extensive research, the progress in developing effective treatments for primary brain tumors lags behind that of other cancers, largely due to the unique challenges of brain tumors (eg, the blood-brain barrier and high heterogeneity) that limit the delivery and efficacy of many therapeutic agents. One way to address this issue is to employ novel trial designs to better optimize the treatment regimen (eg, dose and schedule) in early phase trials to improve the success rate of subsequent phase III trials. The objective of this article is to introduce Bayesian optimal interval (BOIN) designs as a novel platform to design various types of early phase brain tumor trials, including single-agent and combination regimen trials, trials with late-onset toxicities, and trials aiming to find the optimal biological dose (OBD) based on both toxicity and efficacy. Unlike many novel Bayesian adaptive designs, which are difficult to understand and complicated to implement by clinical investigators, the BOIN designs are self-explanatory and user friendly, yet yield more robust and powerful operating characteristics than conventional designs. We illustrate the BOIN designs using a phase I clinical trial of brain tumor and provide software (freely available at www.trialdesign.org) to facilitate the application of the BOIN design.