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评价疫苗效力的免疫学替代终点
作者:金鹏飞 李靖欣 周洋 朱凤才

摘要:

免疫学替代终点是疫苗诱导产生的可预测临床终点事件发生(感染或患病)的免疫学反应(体液或细胞免疫),并在疫苗临床试验中被用于评价疫苗的效力。与观察临床终点的现场效力试验相比,免疫学疫苗试验可以减少研究人群的样本量、缩短临床试验的期限,从而推动了新试验疫苗的上市和研发。鉴于这些原因,建立免疫学替代终点是美国国立卫生研究院以及比尔和梅琳达盖茨基金会确定的14大全球健康挑战之一。本文从免疫学替代终点的定义和评价免疫学替代终点的统计学方法进行较为全面的阐述。

关键词:免疫学替代终点;临床试验;统计学

Abstract:

An immunological surrogate endpoints is a vaccine-induced immune response (either humoral or cellular immune) that predicts protection against clinical endpoints (infection or disease), and can be used to evaluate vaccine efficacy in clinical vaccine trials. Compared with field efficacy trials observing clinical endpoints, immunological vaccine trials could reduce the sample size or shorten the duration of a trial, which promote the license and development of new candidate vaccines. For these reasons, establishing immunological surrogate endpoints is one of 14 Grand Challenges of Global Health of the National Institutes of Health (NIH) and the Bill and Melinda Gates Foundation. From two parts of definition and statistical methods for evaluation of surrogate endpoints, this review provides a more comprehensive description.

Key words: Immunological surrogate endpoints;Clinical trial;Statistical

发表日期:2015/12

引用本文:

图/表:

  • 10.3760/cma.j.issn.0253-9624.2015.12.018.F001:图1 疫苗接种与临床终点事件间的效应机制

    10.3760/cma.j.issn.0253-9624.2015.12.018.F001:图1 疫苗接种与临床终点事件间的效应机制

  • 10.3760/cma.j.issn.0253-9624.2015.12.018.T001:表1 疫苗可预防性疾病的免疫学替代终点水平

    10.3760/cma.j.issn.0253-9624.2015.12.018.T001:表1 疫苗可预防性疾病的免疫学替代终点水平

  • 10.3760/cma.j.issn.0253-9624.2015.12.018.F002:图2 免疫后6周疫苗效力随抗体水平增长倍数(A)和抗体水平(B)变化趋势图[27]

    10.3760/cma.j.issn.0253-9624.2015.12.018.F002:图2 免疫后6周疫苗效力随抗体水平增长倍数(A)和抗体水平(B)变化趋势图[27]

  • 10.3760/cma.j.issn.0253-9624.2015.12.018.F003:图3 疫苗组和安慰剂组IgG抗荚膜多糖抗体水平分布的反向累积曲线[28]

    10.3760/cma.j.issn.0253-9624.2015.12.018.F003:图3 疫苗组和安慰剂组IgG抗荚膜多糖抗体水平分布的反向累积曲线[28]

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