Methods to Advance the HIV Prevention Research Agenda

描述（由申请人提供）：该提案解决了艾滋病毒预防研究中出现的统计挑战。最近在使用不同的抗逆转录病毒药物（PrEP，杀微生物剂和治疗），男性包皮环切术，以及可能的疫苗预防方面取得了值得注意的进展，但进展不大。然而，将这些模式结合起来可能会大大增强其效果。要解决决策者面临的一个关键问题-如何最好地利用这些方式-就需要了解这些方式的综合效果以及影响这些效果的因素。我们建议通过开发有效的方法来分析预防干预措施的观察性和随机研究的数据，并调查可能改变其受益程度的因素，以促进此类研究。要做到这一点，我们建议在各种统计领域，包括因果推理和半参数理论，网络分析和空间分析的方法进行扩展。我们展示了如何从每个领域的新方法中获得的知识可以有助于其他领域的有用性。我们的第一个目标是开发使用基线协变量的方法，以提高效率的相关结果数据的分析，出现在组随机试验（GRT）和纵向研究，这两种类型的研究被广泛用于艾滋病预防研究。由于GRT中的实验单元的数量可能受到资源限制的限制，我们开发了适合小样本和大样本的方法，并考虑了个体和组水平的协变量。我们的第二个目标是从网络样本中估计作为重要流行驱动因素的网络特征。这一目标还考虑了在建立网络集合时使用这种估计数的方法，这对于现实模拟流行病和综合预防干预措施对流行病的影响至关重要。这些调查将有助于评估是否应通过模拟和对研究数据的分析，针对网络特征调整干预措施（如果是，如何调整）。第三个目标是制定方法，利用艾滋病毒监测数据，特别是产前诊所的数据，估计特定年龄艾滋病毒流行率和发病率的空间和时间变化。这些方法有助于评估预防干预措施的部署效果，特别是在不同区域相继推出的干预措施。

DESCRIPTION (provided by applicant): This proposal addresses statistical challenges that arise in HIV prevention research. Recent progress in prevention from different uses of antiretroviral drugs (in PrEP, microbicides, and treatment), male circumcision, and possibly vaccine has been noteworthy but modest. Combining across these modalities, however, might considerably enhance their effects. To address a crucial question facing policy makers--how best to deploy these modalities--requires knowledge of their combined effects and of the factors that impact on these effects. We propose to facilitate such research by developing efficient methods for analysis of data from observational and randomized studies of prevention interventions and for investigation of factors that may modify their degree of benefit. To do so, we propose to extend methods in variety of statistical areas, including causal inference and semiparametric theory, network analysis, and spatial analysis. We show how knowledge gained from new methods in each area can contribute to the usefulness of those in the other areas. Our first aim is to develop methods for using baseline covariates to improve efficiency of analyses of correlated outcome data that arise in group randomized trials (GRTs) and longitudinal studies; both types of studies are widely used in HIV prevention research. Because the number of experimental units in GRTs may be constrained by resource limitations, we develop methods appropriate for small as well as for large samples, and consider both individual- and group-level covariates. Estimation of network features that are important epidemic drivers from network samples is our second aim. This aim also considers methods for using such estimates in the construction of collections of networks--essential for realistic simulation of epidemics and of the impact of combination prevention interventions on them. These investigations will be useful for assessing whether intervention packages should be tailored to network features (and if so how), both through simulation and in analyses of data from research studies. The third aim develops methods for using data from HIV surveillance, especially of antenatal clinics, to estimate spatial and temporal variation in age-specific HIV prevalence and incidence. Such methods can aid in evaluating the impact of deployment of prevention interventions, especially those which are rolled out in sequentially in different regions.