PDF(Pubmed)
Abstract：
The U.S. Food and Drug Administration launched Project Optimus with the aim of shifting the paradigm of dose-finding and selection toward identifying the optimal biological dose that offers the best balance between benefit and risk, rather than the maximum tolerated dose. However, achieving dose optimization is a challenging task that involves a variety of factors and is considerably more complicated than identifying the maximum tolerated dose, both in terms of design and implementation. This article provides a comprehensive review of various design strategies for dose-optimization trials, including phase 1/2 and 2/3 designs, and highlights their respective advantages and disadvantages. In addition, practical considerations for selecting an appropriate design and planning and executing the trial are discussed. The article also presents freely available software tools that can be utilized for designing and implementing dose-optimization trials. The approaches and their implementation are illustrated through real-world examples.
摘要：
美国食品和药物管理局启动了Optimus项目，旨在将剂量发现和选择的范式转变为确定最佳的生物剂量，从而在利益和风险之间提供最佳平衡。而不是最大耐受剂量。然而,实现剂量优化是一项具有挑战性的任务，涉及多种因素，并且比确定最大耐受剂量要复杂得多。无论是在设计和实现方面。本文对剂量优化试验的各种设计策略进行了全面综述，包括阶段1/2和2/3设计，并突出了它们各自的优缺点。此外,讨论了选择适当设计，计划和执行试验的实际考虑。本文还提供了免费可用的软件工具，可用于设计和实施剂量优化试验。通过现实世界的例子说明了这些方法及其实现。
