Rida W N, Lawrence D N
Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Stat Med. 1994;13(19-20):2155-77. doi: 10.1002/sim.4780131922.
Efficacy trials of prophylactic HIV vaccines will be among the most difficult clinical trials ever attempted. Not only will there be challenges with the recruitment and retention of high-risk uninfected individuals, there will be many statistical challenges to the design, conduct, analysis, and interpretation of these trials. General features of an efficacy trial are described, including choice for the primary endpoint and testing for and estimating vaccine efficacy. Secondary objectives of trials are also discussed. These include determining the correlates of protective immunity, assessing the impact of HIV genetic variation on vaccine efficacy, and using biological markers such as viral load and CD4+ lymphocyte cell count to gain insight on a vaccine's ability to prevent or delay disease. The use of biological markers as surrogates for disease outcome is discussed. Last, trial designs for studying several candidate vaccines or other HIV prevention strategies in a single trial are examined.
预防性HIV疫苗的疗效试验将是有史以来最具挑战性的临床试验之一。不仅在招募和留住未感染的高危个体方面会面临挑战，在这些试验的设计、实施、分析和解读上还会有诸多统计学挑战。文中描述了疗效试验的一般特征，包括主要终点的选择以及疫苗疗效的检测和评估。还讨论了试验的次要目标。这些目标包括确定保护性免疫的相关因素、评估HIV基因变异对疫苗疗效的影响，以及使用病毒载量和CD4+淋巴细胞计数等生物标志物来深入了解疫苗预防或延缓疾病的能力。文中讨论了使用生物标志物作为疾病结局替代指标的情况。最后，研究了在单一试验中研究多种候选疫苗或其他HIV预防策略的试验设计。
