Chow Shein-Chung, Huang Zhipeng
Department of Biostatistics and Bioinformatics, Duke University School of Medicine , Durham , North carolina , USA.
Statistician , Silver Spring , Maryland , USA.
J Biopharm Stat. 2019;29(5):897-907. doi: 10.1080/10543406.2019.1657137. Epub 2019 Aug 27.
For review and approval of new drug products, substantial evidence regarding safety and effectiveness of the drug products under investigation are necessarily provided. A traditional approach is to test a null hypothesis of against an alternative hypothesis of at the 5% level of significance. The rejection of the null hypothesis of ineffectiveness is in favor of the alternative hypothesis of effectiveness. This approach, however, is somewhat misleading because the rejection of the null hypothesis of ineffectiveness leads to the conclusion of , which consists of the proportion of inconclusiveness and the proportion of effectiveness. In this article, we explore the potential use of the concept of demonstrating and then for regulatory approval of new drug products, especially for rare disease drug products. For rare disease drug product development, one of the major obstacles and challenges is how to use small patient population available for achieving the same standards for regulatory approval. To address this problem, a two-stage approach by first demonstrating not ineffectiveness and then ruling out (or controlling) the probability of inconclusiveness for demonstrating effectiveness is proposed. The proposed two-stage approach is useful with small patient population available for achieving the same standards for regulatory approval of rare disease drug products.
对于新药产品的审评和批准，必须提供有关正在研究的药品安全性和有效性的充分证据。传统方法是在5%的显著性水平下，针对无效的原假设 检验备择假设 。拒绝无效的原假设即支持有效性的备择假设。然而，这种方法存在一定误导性，因为拒绝无效的原假设会得出 的结论，其中包括不确定性比例和有效性比例。在本文中，我们探讨了利用先证明 然后证明 的概念用于新药产品监管批准的可能性，特别是针对罕见病药品。对于罕见病药品研发，主要障碍和挑战之一是如何利用有限的患者群体达到相同的监管批准标准。为解决这一问题，我们提出了一种两阶段方法，首先证明并非无效，然后排除（或控制）证明有效性时的不确定性概率。所提出的两阶段方法对于利用有限患者群体达到罕见病药品监管批准的相同标准很有用。
