Statistical Data Analysis Center, Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI 53726-2397, USA.
Prog Cardiovasc Dis. 2012 Jan-Feb;54(4):343-50. doi: 10.1016/j.pcad.2011.09.007.
A surrogate end point is one that is used as a substitute for a clinical end point of more direct interest, usually for reasons of practicality, and that is expected to predict clinical benefit. Surrogate end points play a critical role in the advancement of all medical research, and cardiovascular (CV) research in particular. However, the relationship between a surrogate end point and its clinical end point is usually complex, and there are many examples where results based on surrogates have proved to be misleading. Secondary analyses of existing clinical trial data are likely to involve surrogate end points, if only because clinical end points will have been extensively studied as part of the primary analysis of a trial large enough to collect useful clinical end point data. Validation of a surrogate end point is a laudable goal for a secondary analysis of a large clinical end point trial (or meta-analysis of multiple smaller trials), and the result may be an important new tool for further study of a class of compounds in a particular disease context. Secondary analyses using surrogate end points may also provide new insight into disease or treatment mechanism, but as with any surrogate end point analysis, the results can mislead, and the existing literature is heavy on application and light on methodology. Surrogate end points often substitute efficiency for clarity, and while many interesting and potentially informative secondary analyses of CV trials will involve surrogates, results are likely to be ambiguous and should be interpreted with care.
替代终点是一种被用作更直接相关的临床终点的替代物，通常是出于实际原因，并且预计可以预测临床获益。替代终点在所有医学研究中都起着至关重要的作用，尤其是心血管（CV）研究。然而，替代终点与其临床终点之间的关系通常很复杂，并且有许多基于替代终点的结果被证明是误导性的例子。对现有临床试验数据的二次分析可能涉及替代终点，即使只是因为临床终点已经作为试验的主要分析的一部分进行了广泛研究，该试验足够大，可以收集有用的临床终点数据。对于大型临床终点试验（或多个较小试验的荟萃分析）的二次分析，验证替代终点是一个值得称赞的目标，其结果可能是在特定疾病背景下进一步研究一类化合物的重要新工具。使用替代终点的二次分析也可能为疾病或治疗机制提供新的见解，但与任何替代终点分析一样，结果可能会产生误导，并且现有文献在应用方面很丰富，而在方法学方面却很少。替代终点通常以效率代替清晰度，虽然许多有趣且潜在有信息量的 CV 试验的二次分析将涉及替代终点，但结果可能是模棱两可的，并且应该谨慎解释。
