Practical experiences of adopting assurance as a quantitative framework to support decision making in drug development
Practical experiences of adopting assurance as a quantitative framework to support decision making in drug development
复制标题
DOI：
10.1002/pst.1856
复制
发表时间：
2018-07-01
影响因子：
1.5
通讯作者：
Best, Nicky
中科院分区：
文献类型：
--
作者：
Crisp, Adam;Miller, Sam;Best, Nicky
所有临床试验的设计都是为了实现其主要目标。因此，评估成功概率（PoS）应该是设计阶段的一个关键重点，以支持申办者管理委员会的资金批准，并为试验设计本身提供信息。近年来，在整个行业中，使用保证（即，在治疗效果的先验概率分布上平均的预期成功概率）来量化计划研究的PoS的做法越来越多，现在已经成为作者公司的常规做法。在本文中，我们通过几个案例研究说明了系统地采用保证作为定量框架来支持药物开发决策的一些好处，其中保证评估已被证明在试验设计和支持治理委员会审查方面具有影响力项目提案。此外，我们描述了如何在我们公司内实施保证框架的具体特征，突出了先前启发在此过程中发挥的关键作用，并说明了如何将整体保证计算分解为一系列有条件的PoS估计，从而更深入地了解不同的开发选项如何以及何时能够释放风险。
All clinical trials are designed for success of their primary objectives. Hence, evaluating the probability of success (PoS) should be a key focus at the design stage both to support funding approval from sponsor governance boards and to inform trial design itself. Use of assurancethat is, expected success probability averaged over a prior probability distribution for the treatment effectto quantify PoS of a planned study has grown across the industry in recent years, and has now become routine within the authors' company. In this paper, we illustrate some of the benefits of systematically adopting assurance as a quantitative framework to support decision making in drug development through several case-studies where evaluation of assurance has proved impactful in terms of trial design and in supporting governance-board reviews of project proposals. In addition, we describe specific features of how the assurance framework has been implemented within our company, highlighting the critical role that prior elicitation plays in this process, and illustrating how the overall assurance calculation may be decomposed into a sequence of conditional PoS estimates which can provide greater insight into how and when different development options are able to discharge risk.