In early phase clinical trial, finding maximum-tolerated dose (MTD) is a very important goal. Many researches show that finding a correct MTD can improve drug efficacy and safety significantly. Usually, dose-finding trials start from very low doses, so in many cases, more than 50% patients or cohorts do not have dose-limiting toxicity (DLT), but DLT may occur suddenly and increase fast along with just two or three doses. Although some fantastic models were built to find MTD, little consideration was given to those '0 DLTs' and the 'jump' of DLTs. In this paper, we developed a Bayesian zero-inflated binomial regression for dose-finding study, which analyses dose-finding data from two aspects: 1) observation of only zeros, 2) number of DLTs based on binomial distribution, so it can help us analyse if the cohorts without DLT have potential possibility to have DLT and fit the 'jump' of DLTs.

译文

:在早期临床试验中,找到最大耐受剂量(MTD)是非常重要的目标。许多研究表明,找到正确的MTD可以显着提高药物疗效和安全性。通常,剂量寻找试验从非常低的剂量开始,因此在许多情况下,超过50%的患者或队列没有剂量限制性毒性(DLT),但是DLT可能突然发生并且仅以两或三剂就可以快速增加。尽管构建了一些出色的模型来查找MTD,但很少考虑那些“ 0 DLT”和DLT的“跳跃”。在本文中,我们开发了用于剂量查找研究的贝叶斯零膨胀二项式回归,它从两个方面分析了剂量查找数据:1)仅观察零,2)基于二项式分布的DLT数量,因此可以提供帮助我们分析了没有DLT的人群是否有可能拥有DLT并适应DLT的“跳跃”。

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