Better decision making in drug development through adoption of formal prior elicitation
Better decision making in drug development through adoption of formal prior elicitation
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DOI：
10.1002/pst.1854
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发表时间：
2018-07-01
影响因子：
1.5
通讯作者：
Montague, Timothy H.
中科院分区：
文献类型：
--
作者：
Dallow, Nigel;Best, Nicky;Montague, Timothy H.
随着贝叶斯方法在药物开发中的使用不断增加，统计学家需要有工具来开发强大的和可辩护的信息先验分布。虽然相关的经验数据应该在可能的情况下为这种先验提供基础，但通常情况下，数据和/或我们的理解的局限性可能会妨碍直接构建基于数据的先验。正式的专家启发方法是一个关键技术，可以用来确定在这些情况下的先验知识。在葛兰素史克内部，我们采用了一种基于SHELF启发框架的结构化方法来进行先前的启发，并定期将其与下一项研究的成功概率（保证）计算结合使用，以告知关键项目里程碑的内部决策。本文的目的是分享我们的经验，嵌入使用事先启发在一个大型制药公司，突出了事先启发的好处和挑战，通过一系列的案例研究。我们发现，将团队信念转化为定量概率分布的形式，为所有内部决策提供了一个坚实的锚，使团队能够为投资委员会提供正式适当的试验成功概率估计，以及适当的中期决策规则的稳健计划。作为一个额外的好处，启发过程提供了关于潜在药物的信念和风险的透明度，最终实现更好的投资组合和公司范围的决策。
With the continued increase in the use of Bayesian methods in drug development, there is a need for statisticians to have tools to develop robust and defensible informative prior distributions. Whilst relevant empirical data should, where possible, provide the basis for such priors, it is often the case that limitations in data and/or our understanding may preclude direct construction of a data-based prior. Formal expert elicitation methods are a key technique that can be used to determine priors in these situations. Within GlaxoSmithKline, we have adopted a structured approach to prior elicitation on the basis of the SHELF elicitation framework and routinely use this in conjunction with calculation of probability of success (assurance) of the next study(s) to inform internal decision making at key project milestones. The aim of this paper is to share our experiences of embedding the use of prior elicitation within a large pharmaceutical company, highlighting both the benefits and challenges of prior elicitation through a series of case studies. We have found that putting team beliefs into the shape of a quantitative probability distribution provides a firm anchor for all internal decision making, enabling teams to provide investment boards with formally appropriate estimates of the probability of trial success as well as robust plans for interim decision rules where appropriate. As an added benefit, the elicitation process provides transparency about the beliefs and risks of the potential medicine, ultimately enabling better portfolio and company-wide decision making.