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arXiv 2406.03596stat.ME
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基于马氏距离与数据驱动边界的多元等效性检验

A Multivariate Equivalence Test Based on Mahalanobis Distance with a Data-Driven Margin

Chao Wang, Yu-Ting Weng, Shaobo Liu, Tengfei Li, Meiyu Shen, Yi Tsong

AI总结:

本文针对多成分药品的等效性评估问题,提出一种基于马氏距离且考虑数据驱动边界随机性的多元等效性检验方法,并通过大量模拟研究验证其相对于现有方法的性能。

摘要:

在药物开发的多种场景中都需要进行多元等效性检验。例如,从天然来源获得的药品可能包含许多成分,而这些成分对临床疗效和安全性的个体效应和/或相互作用无法被完全表征。这种充分表征的缺乏给仿制药开发者证明其拟议仿制药与参比制剂的相同性以及监管机构判定这种相同性都带来了挑战。另一种情况是确保含有大量成分的天然来源产品(如植物药产品)的批间一致性。对于含有许多无法单独评估成分的产品之间的等效性或相同性,需要以整体方式进行研究。基于马氏距离的多元等效性检验可能适合整体评估多个变量。基于该方法已有研究要么假设预先确定的常数边界(对此很难达成共识),要么采用从数据推导出的边界,但在检验过程中忽略了随机性。在本研究中,我们提出了一种基于马氏距离的多元等效性检验,采用数据驱动边界,并考虑了边界中的随机性。通过广泛的模拟研究,将几种可能的实现方式与现有方法进行了比较。

英文摘要:

Multivariate equivalence testing is needed in a variety of scenarios for drug development. For example, drug products obtained from natural sources may contain many components for which the individual effects and/or their interactions on clinical efficacy and safety cannot be completely characterized. Such lack of sufficient characterization poses a challenge for both generic drug developers to demonstrate and regulatory authorities to determine the sameness of a proposed generic product to its reference product. Another case is to ensure batch-to-batch consistency of naturally derived products containing a vast number of components, such as botanical products. The equivalence or sameness between products containing many components that cannot be individually evaluated needs to be studied in a holistic manner. Multivariate equivalence test based on Mahalanobis distance may be suitable to evaluate many variables holistically. Existing studies based on such method assumed either a predetermined constant margin, for which a consensus is difficult to achieve, or a margin derived from the data, where, however, the randomness is ignored during the testing. In this study, we propose a multivariate equivalence test based on Mahalanobis distance with a data-drive margin with the randomness in the margin considered. Several possible implementations are compared with existing approaches via extensive simulation studies.

机构、总结、中文摘要均由AI分析而来,可能存在错误,请以论文正文为准。

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