On the Relationship between the Causal-Inference and Meta-Analytic Paradigms for the Validation of Surrogate Endpoints
On the Relationship between the Causal-Inference and Meta-Analytic Paradigms for the Validation of Surrogate Endpoints
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DOI：
10.1111/biom.12245
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发表时间：
2015-03-01
期刊：
影响因子：
1.9
通讯作者：
Burzykowski, Tomasz
中科院分区：
文献类型：
--
作者：
Alonso, Ariel;Van der Elst, Wim;Burzykowski, Tomasz
随着药物开发成本的增加，在临床试验中评估新药时，对替代终点的需求也随之增加。然而，多年来，很明显，替代终点需要进行统计学评估并被认为是有效的，然后才能在临床研究中用作真实终点的替代品。如今，两种范式，基于因果推理和元分析，占主导地位的场景。尽管如此，尽管从这些范式产生的文献是广泛的，到现在为止，它们之间的关系在很大程度上是未被探索的。在目前的工作中，我们讨论了这两种方法的概念框架，并使用理论元素和真实的案例研究的分析，研究它们之间的关系。此外，我们表明，元分析方法可以嵌入在一个因果推理框架内，一方面，它可以被证明是合理的，为什么使用这种方法成功评估的替代终点往往是有吸引力的因果推理的角度来看，以及，另一方面。一个新开发的和用户友好的R包替代提供进行评估工作。
The increasing cost of drug development has raised the demand for surrogate endpoints when evaluating new drugs in clinical trials. However, over the years, it has become clear that surrogate endpoints need to be statistically evaluated and deemed valid, before they can be used as substitutes of true endpoints in clinical studies. Nowadays, two paradigms, based on causal-inference and meta-analysis, dominate the scene. Nonetheless, although the literature emanating from these paradigms is wide, till now the relationship between them has largely been left unexplored. In the present work, we discuss the conceptual framework underlying both approaches and study the relationship between them using theoretical elements and the analysis of a real case study. Furthermore, we show that the meta-analytic approach can be embedded within a causal-inference framework on the one hand and that it can be heuristically justified why surrogate endpoints successfully evaluated using this approach will often be appealing from a causal-inference perspective as well, on the other. A newly developed and user friendly R package Surrogate is provided to carry out the evaluation exercise.