引发对相关感兴趣量的判断：使用哮喘病例研究说明的SHELF扩展和copula方法
Eliciting judgements about dependent quantities of interest: The SHELF extension and copula methods illustrated using an asthma case study
摘要：
制药公司经常需要根据早期临床试验的有限知识来决定药物开发计划。在这种情况下，引起专家的判断是一个有吸引力的方法来综合证据的未知量的兴趣。在计算药物开发项目的成功概率时，多个感兴趣的量-例如药物对不同终点的影响-不应被视为无关。我们讨论了两种方法，建立一个多元分布的几个相关的量在谢菲尔德诱导框架（SHELF）。第一种方法将专家对一个兴趣量的判断以另一个兴趣量的知识为条件。对于第二种方法，我们首先得出每个感兴趣的量的边缘分布。然后，对于每一对量，我们得出一致性概率，即两者都位于各自得出的中位数的同一侧。这允许我们指定一个copula来获得感兴趣的量的联合分布。我们展示了这些方法是如何用于启发式研讨会，进行评估成功的哮喘药物的注册计划的概率。在关键研究完成之前获得的专家判断与最终试验结果完全一致。
英文摘要：
Pharmaceutical companies regularly need to make decisions about drug development programs based on the limited knowledge from early stage clinical trials. In this situation, eliciting the judgements of experts is an attractive approach for synthesising evidence on the unknown quantities of interest. When calculating the probability of success for a drug development program, multiple quantities of interest - such as the effect of a drug on different endpoints - should not be treated as unrelated. We discuss two approaches for establishing a multivariate distribution for several related quantities within the SHeffield ELicitation Framework (SHELF). The first approach elicits experts' judgements about a quantity of interest conditional on knowledge about another one. For the second approach, we first elicit marginal distributions for each quantity of interest. Then, for each pair of quantities, we elicit the concordance probability that both lie on the same side of their respective elicited medians. This allows us to specify a copula to obtain the joint distribution of the quantities of interest. We show how these approaches were used in an elicitation workshop that was performed to assess the probability of success of the registrational program of an asthma drug. The judgements of the experts, which were obtained prior to completion of the pivotal studies, were well aligned with the final trial results.
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