Surrogate markers are often used in clinical trials settings when obtaining a final outcome to evaluate the effectiveness of a treatment requires a long wait, is expensive to obtain, or both. Formal definitions of surrogate marker quality resulting from a large variety of estimation approaches have been proposed over the years. I review this work, with a particular focus on approaches that use the causal inference paradigm, as these conceptualize a good marker as one in the causal pathway between the treatment and outcome. I also focus on efforts to evaluate the risk of a surrogate paradox, a damaging situation where the surrogate is positively associated with the outcome, and the causal effect of the treatment on the surrogate is in a helpful direction, but the ultimate causal effect of the treatment on the outcome is harmful. I then review some recent work in robust surrogate marker estimation and conclude with a discussion and suggestions for future research.

中文翻译：

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临床试验中的替代终点


当获得最终结果以评估治疗的有效性需要长时间等待、获得成本高或两者兼而有之时，替代标志物通常用于临床试验环境中。多年来，已经提出了由多种估计方法得出的替代标记质量的正式定义。我回顾了这项工作，特别关注使用因果推理范式的方法，因为这些方法将一个好的标志物概念化为治疗和结果之间的因果途径中的一个标志物。我还专注于评估替代悖论的风险，这是一种破坏性的情况，其中替代者与结果呈正相关，并且治疗对替代者的因果影响是有益的，但治疗对结果的最终因果影响是有害的。然后，我回顾了最近在稳健替代标记估计方面的一些工作，并对未来的研究进行了讨论和建议。