Gilbert P B
Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
Stat Methods Med Res. 2000 Jun;9(3):207-29. doi: 10.1177/096228020000900303.
This article summarizes material on statistical issues in the design of HIV-1 preventive vaccine trials and antiretroviral HIV-1 treatment trials that was presented at the first school on Modern Statistical Methods in Medical Research, held at the International Centre for Theoretical Physics in Trieste, in September 1999. Design issues for the two trial types are discussed separately and are compared, which highlights the relative complexity of vaccine trials. Vaccine trial designs for assessing various vaccine effects are considered, including classical double-blind individual-randomized designs for evaluating biological vaccine effects on susceptibility to infection, and augmented partners, cluster-randomized, and infant designs for evaluating biological vaccine effects on infectiousness as well as on susceptibility. Within these designs, covered topics include surrogate endpoints for measuring vaccine effects on secondary transmission and on HIV-1 disease progression, and exploratory and confirmatory methods for assessing host immune and viral genotypic or phenotypic correlates of vaccine protection against infection or disease. For antiretroviral trials, covered topics include endpoint selection and structured designs such as fractional factorial and Latin square designs for rapidly screening combination drug regimens and for identifying patterns of HIV-1 genomic evolution that predict loss of drug efficacy.
本文总结了1999年9月在的里雅斯特国际理论物理中心举办的首届医学研究现代统计方法研讨会上所展示的关于HIV-1预防性疫苗试验和抗逆转录病毒HIV-1治疗试验设计中的统计问题的材料。分别讨论并比较了这两种试验类型的设计问题，这凸显了疫苗试验相对的复杂性。考虑了用于评估各种疫苗效果的疫苗试验设计，包括用于评估生物疫苗对感染易感性影响的经典双盲个体随机设计，以及用于评估生物疫苗对传染性和易感性影响的扩大伴侣、整群随机和婴儿设计。在这些设计中，涵盖的主题包括用于衡量疫苗对二次传播和HIV-1疾病进展影响的替代终点，以及用于评估疫苗预防感染或疾病的宿主免疫和病毒基因型或表型相关性的探索性和验证性方法。对于抗逆转录病毒试验，涵盖的主题包括终点选择和结构化设计，如分数析因设计和拉丁方设计，用于快速筛选联合药物方案以及识别预测药物疗效丧失的HIV-1基因组进化模式。
