Wittes J, Lakatos E, Probstfield J
Biostatistics Research Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.
Stat Med. 1989 Apr;8(4):415-25. doi: 10.1002/sim.4780080405.
A surrogate endpoint in a cardiovascular clinical trial is defined as endpoint measured in lieu of some other so-called 'true' endpoint. A surrogate is especially useful if it is easily measured and highly correlated with the true endpoint. Often the 'true' endpoint is one with clinical importance to the patient, for example, mortality or a major clinical outcome, while a surrogate is one biologically closer to the process of disease, for example, ejection fraction. Use of the surrogate can often lead to dramatic reductions in sample size and much shorter studies than use of the true endpoint. We discuss several problems common in trials with surrogate endpoints. Most important is the effect of missing data, especially in the face of informative censoring. Possible solutions are the assignment of scores or formal penalties to missing data.
心血管临床试验中的替代终点被定义为代替某些其他所谓“真实”终点进行测量的终点。如果替代终点易于测量且与真实终点高度相关，那么它就特别有用。通常，“真实”终点是对患者具有临床重要性的终点，例如死亡率或主要临床结局，而替代终点在生物学上更接近疾病过程，例如射血分数。使用替代终点通常可以使样本量大幅减少，并且研究时间比使用真实终点时短得多。我们讨论了替代终点试验中常见的几个问题。最重要的是缺失数据的影响，尤其是在面对信息删失的情况下。可能的解决办法是对缺失数据进行评分或给予正式惩罚。
