Adaptivity in Drug Discovery and Development
Adaptivity in Drug Discovery and Development
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DOI：
10.1002/ddr.20285
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发表时间：
2009-05-01
影响因子：
3.8
通讯作者：
Coffey, Christopher S.
中科院分区：
文献类型：
--
作者：
Bretz, Frank;Branson, Michael;Coffey, Christopher S.
新药的开发正变得越来越具有挑战性、效率低下和成本高昂，这是制药产品的所有主要利益相关者都承认的。适应性设计近年来吸引了相当多的关注，因为它们有望通过更好地利用观察到的数据来提高药物开发过程的效率。适应性设计的关键思想是使用从正在进行的实验中积累的数据来决定如何修改某些设计方面，更好地解决感兴趣的问题和/或调整不正确的假设。当仔细计划并在适当的情况下应用时，许多适应性设计允许科学合理的结论：早期停止无效或成功，样本量重新评估，治疗选择等。然而，目前大多数关于适应性设计的讨论都集中在新药开发（后期）阶段的临床试验应用上。这篇综述的目的是拓宽这一视角，并证明适应性是一个基本的重要概念，可以应用于药物发现和开发的许多不同阶段。我们回顾了可用于规划和分析适应性设计的主要统计方法，然后通过药物发现和开发过程并确定适应性的可能机会。为了说明这些想法，我们参考了文献中的例子和案例研究。本文还简要讨论了监管角度、操作方面和一些潜在障碍。医药科学进展，2009(7):379 - 379。(C) 2009 Wiley-Liss, Inc。
The development of novel drugs is becoming increasingly challenging, inefficient, and costly, as acknowledged by all major stakeholders of pharmaceutical products. Adaptive designs have attracted considerable attention in recent years, as they promise an increase in efficiency of the drug development process by making better use of the observed data. The key idea of adaptive designs is to use data accumulating from an ongoing experiment to decide on how to modify certain design aspects and better address the question(s) of interest and/or adjust for incorrect assumptions. When planned carefully and applied in appropriate situations, a number of adaptive designs allow for scientifically sound conclusions: early stopping either for futility or for success, sample size reassessment, treatment selection, etc. Most of the current discussions regarding adaptive designs, focus however, on clinical trial applications in the (late) development phase of a novel drug. The aim of this review is to broaden this perspective and to demonstrate that adaptivity is a fundamentally important concept that can be applied to many different stages of drug discovery and development. We review the major statistical methods available for planning and analyzing adaptive designs and then move through the drug discovery and development process and identify possible opportunities for adaptivity. To illustrate the ideas, we refer to examples and case studies from the literature, where available. A brief discussion about regulatory perspectives, operational aspects, and some potential hurdles is also given. Drug Dev Res 70:169-190,2009. (C) 2009 Wiley-Liss, Inc.