Hughes M D, DeGruttola V, Welles S L
Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
J Acquir Immune Defic Syndr Hum Retrovirol. 1995;10 Suppl 2:S1-8.
We discuss approaches for efficiently evaluating potential surrogate markers; in particular, we focus on case-cohort designs in which marker evaluation is undertaken only for a random sample of subjects within a randomized trial and for all other subjects who develop a major clinical outcome. These designs will be useful in clinical trials in which a highly significant treatment difference on clinical outcome has been obtained. In addition, we describe a method for using data from all available studies using a meta-analysis to explore the association of treatment effects on the potential marker and on clinical outcome. This may be the most effective approach for marker evaluation because it uses data from both large and small trials and incorporates information from trials in which nonsignificant treatment differences on the major clinical outcome are obtained.
我们讨论了有效评估潜在替代标志物的方法；特别地，我们关注病例队列设计，即在随机试验中仅对受试者的随机样本以及所有发生主要临床结局的其他受试者进行标志物评估。这些设计在已获得临床结局上具有高度显著治疗差异的临床试验中将会有用。此外，我们描述了一种使用荟萃分析从所有可用研究中获取数据的方法，以探究治疗效果与潜在标志物以及临床结局之间的关联。这可能是评估标志物最有效的方法，因为它使用了来自大型和小型试验的数据，并纳入了在主要临床结局上未获得显著治疗差异的试验中的信息。
