Perspective: Validating surrogate markers - Are we being naive?
Perspective: Validating surrogate markers - Are we being naive?
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DOI：
10.1093/infdis/175.2.237
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发表时间：
1997-02-01
影响因子：
6.4
通讯作者：
Coombs, R
中科院分区：
文献类型：
--
作者：
DeGruttola, V;Fleming, T;Coombs, R
Because of the difficulties in conducting studies of clinical efficacy of new therapies for human immunodeficiency virus infection and other;diseases, there is increasing interest in using measures of biologic activity as surrogates for clinical end points. A widely used criterion for evaluating whether such measures are reliable as surrogates requires that the putative surrogate fully captures the ''net effect''-the effect aggregated over all mechanisms of action-of the treatment on the clinical end point. The variety of proposed metrics for evaluating the degree to which this criterion is met are subject to misinterpretation because of the multiplicity of mechanisms by which drugs operate. Without detailed understanding of these mechanisms, metrics of ''surrogacy'' are not directly interpretable. Even when all of the mechanisms are understood, these metrics are associated with a high degree of uncertainty unless either treatment effects are large in moderate-size studies or sample sizes are large in studies of moderately effective treatments.
