Long Dustin M, Hudgens Michael G, Wu Chih-Da
Department of Biostatistics, West Virginia University, Morgantown, WV, U.S.A.
Stat Med. 2015 May 10;34(10):1747-60. doi: 10.1002/sim.6436. Epub 2015 Jan 28.
A critical step toward developing a successful vaccine to control the human immunodeficiency virus pandemic entails evaluation of vaccine candidates in non-human primates (NHPs). Historically, these studies have usually entailed challenges (i.e., exposures) with very high doses of a simian version of human immunodeficiency virus, resulting in infection of all NHPs in the experiment after a single challenge. More recently, researchers have begun to conduct repeated low-dose challenge (RLC) studies in NHPs that are believed to more closely mimic typical exposure in natural human transmission settings. One objective of RLC studies is to assess whether measured immune responses to vaccination can serve as surrogate endpoints for the primary endpoint of interest, namely infection. In this paper, different designs of RLC studies for assessing a binary surrogate of protection are considered.
开发一种成功的疫苗以控制人类免疫缺陷病毒大流行的关键一步是在非人类灵长类动物（NHP）中评估候选疫苗。从历史上看，这些研究通常需要用非常高剂量的猿类版本的人类免疫缺陷病毒进行攻毒（即暴露），导致在单次攻毒后实验中的所有NHP都被感染。最近，研究人员开始在NHP中进行重复低剂量攻毒（RLC）研究，据信这种研究更接近模拟人类自然传播环境中的典型暴露。RLC研究的一个目标是评估对疫苗接种所测得的免疫反应是否可以作为感兴趣的主要终点（即感染）的替代终点。在本文中，考虑了用于评估保护二元替代指标的不同RLC研究设计。
