Does the Prentice criterion validate surrogate endpoints?
Does the Prentice criterion validate surrogate endpoints?
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DOI：
10.1002/sim.1780
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发表时间：
2004-05-30
影响因子：
2
通讯作者：
Berger, VW
中科院分区：
文献类型：
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作者：
Berger, VW
基于临床终点（如生存时间）的随机II期或III期临床试验可能过于昂贵，无论是完成所需的时间还是所需的患者数量。因此，替代终点，如客观肿瘤反应或标志物，包括前列腺特异性抗原或CA-125，在临床试验中得到了广泛的普及。如果替代终点的改善本身并不能使患者获益，则必须考虑替代终点的改善在多大程度上意味着真正关注的临床终点的改善。这不是一个微不足道的问题，由NIH赞助的抗心律失常药物试验的结果证明了这一点，在该试验中，纠正不规则心跳的能力不仅没有对应于生存益处，而且实际上导致了过高的死亡率。验证替代终点的一种方法涉及确保替代终点的有效组间分析也构成真实临床终点的有效分析。普伦蒂斯标准是一组条件，基本上规定了治疗对真实终点的影响的条件独立性，给定了替代终点。结果表明，仅该标准就可确保观察到的治疗对真实终点的影响意味着治疗对替代终点也有影响，但与流行的观点相反，它并不能确保匡威的情况，特别是观察到的对替代终点的显著治疗效果可用于推断对真实终点的治疗效果。出版社：John Wiley Sons，Ltd.
Randomized Phase II or Phase III clinical trials that are powered based on clinical endpoints, such as survival time, may be prohibitively expensive, in terms of both the time required for their completion and the number of patients required. As such, surrogate endpoints, such as objective tumour response or markers including prostate specific antigen or CA-125, have gained widespread popularity in clinical trials. If an improvement in a surrogate endpoint does not itself confer patient benefit, then consideration must be given to the extent to which improvement in a surrogate endpoint implies improvement in the true clinical endpoint of interest. That this is not a trivial issue is demonstrated by the results of an NIH-sponsored trial of anti-arrhythmic drugs, in which the ability to correct an irregular heart beat not only did not correspond to a survival benefit but in fact led to excess mortality. One approach to the validation of surrogate endpoints involves ensuring that a valid between-group analysis of the surrogate endpoint constitutes also a valid analysis of the true clinical endpoint. The Prentice criterion is a set of conditions that essentially specify the conditional independence of the impact of treatment on the true endpoint, given the surrogate endpoint. It is shown that this criterion alone ensures that an observed effect of the treatment on the true endpoint implies a treatment effect also on the surrogate endpoint, but contrary to popular belief, it does not ensure the converse, specifically that the observation of a significant treatment effect on the surrogate endpoint can be used to infer a treatment effect on the true endpoint. Published in 2004 by John Wiley Sons, Ltd.