Research and Development, Sanofi , Chilly-Mazarin, France.
IMAG, Univ Montpellier, CNRS , Montpellier, France.
J Biopharm Stat. 2020 Jul 3;30(4):662-673. doi: 10.1080/10543406.2020.1730874. Epub 2020 Mar 17.
Dose selection is one of the most difficult and crucial decisions to make during drug development. As a consequence, the dose-finding trial is a major milestone in the drug development plan and should be properly designed. This article will review the most recent methodologies for optimizing the design of dose-finding studies: all of them are based on the modeling of the dose-response curve, which is now the gold standard approach for analyzing dose-finding studies instead of the traditional ANOVA/multiple testing approach. We will address the optimization of both fixed and adaptive designs and briefly outline new methodologies currently under investigation, based on utility functions.
剂量选择是药物开发过程中最困难和最关键的决策之一。因此，剂量探索试验是药物开发计划中的一个重要里程碑，应该进行适当的设计。本文将回顾最近用于优化剂量探索研究设计的方法学：所有这些方法都基于剂量-反应曲线的建模，这是目前分析剂量探索研究的黄金标准方法，而不是传统的方差分析/多重检验方法。我们将讨论固定和自适应设计的优化，并简要概述基于效用函数的当前正在研究的新方法学。
