Longini I M, Datta S, Halloran M E
Department of Biostatistics, Rollins School of Public Health, Emory University, Atlanta, Georgia 30322, USA.
J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Dec 15;13(5):440-7. doi: 10.1097/00042560-199612150-00007.
Current Phase III trials are designed to assess only a vaccine candidate's ability to reduce susceptibility to infection or disease, that is, vaccine efficacy for susceptibility (VES). Human immunodeficiency virus (HIV) vaccination, however, may reduce the level of infectiousness of vaccinees who become infected, producing an important indirect reduction in HIV transmission even if the vaccine confers only modest protection against infection. We propose two approaches for augmenting the information of a classic trial for estimating protective efficacy that enable the additional estimation of the vaccine's effect on infectiousness, that is, vaccine efficacy for infectiousness (VEI). In the first augmentation, steady sexual partners of trial participants are recruited but not randomized to vaccine or placebo. Their infection status is monitored throughout the trial. In the second augmentation, the sexual partners are randomized. Through computer simulations and analytic methods, we investigate the feasibility and statistical properties of the augmented designs. Phase III prophylactic HIV-1 vaccines trials are currently being planned. Employment of the augmented designs described in this paper would not only provide estimation of VEI but also increase the precision of the VES estimator and the power to reject the null hypothesis of no vaccine effect.
当前的III期试验仅旨在评估候选疫苗降低感染易感性或疾病易感性的能力，即疫苗对易感性的效力（VES）。然而，人类免疫缺陷病毒（HIV）疫苗接种可能会降低已感染疫苗接种者的传染性水平，即使该疫苗仅提供适度的感染防护，也会在HIV传播方面产生重要的间接降低作用。我们提出了两种方法来增强经典试验的信息，以估计保护效力，从而能够额外估计疫苗对传染性的影响，即疫苗对传染性的效力（VEI）。在第一种增强方法中，招募试验参与者的固定性伴侣，但不将其随机分配至疫苗组或安慰剂组。在整个试验过程中监测他们的感染状况。在第二种增强方法中，将性伴侣随机分组。通过计算机模拟和分析方法，我们研究了增强设计的可行性和统计特性。目前正在规划III期预防性HIV-1疫苗试验。采用本文所述的增强设计不仅能够提供VEI的估计值，还能提高VES估计量的精度以及拒绝无疫苗效果零假设的检验效能。
