Statistical Methods to Study the Impact of HIV Interventions

评价预防和治疗艾滋病毒的新方法仍然是一项紧迫的公共卫生优先事项，特别是在撒哈拉以南非洲地区。有效进行这种评价的能力要求开发新的统计方法，能够解决艾滋病毒研究所需数据的独特复杂性。这包括来自基于人口的调查以及预防和治疗干预措施的随机对照试验的数据。我们建议追求方法发展的三个途径，以推进这一研究议程。首先，我们将开发使用基于人口的调查数据来估计人口包皮环切干预措施的潜在影响的方法，并将这些方法应用于莱索托的数据。其次，我们将开发用于估计联合终点治疗效果的方法，这些联合终点由临床试验人群中不定期监测的事件组成，因此需要进行信息区间删失。这些技术将使用博茨瓦纳Tshepo试验的数据进行开发和说明。第三，我们将开发和比较方法，以估计特定的因果途径的随机艾滋病毒预防干预措施的效果的贡献。我们将这些方法应用于津巴布韦和南非的一项隔膜使用随机对照试验的数据，以估计隔膜对HIV传播的影响，控制隔膜对避孕套使用的意外影响。每一个具体的目标是由一个具体的公共卫生问题，我们预计在每一种情况下，拟议的研究结果将提供一个有价值的应用贡献与相当大的影响的潜力。与此同时，每个目标的更大目标是制定一套通用的实用方法，广泛适用于艾滋病毒预防和治疗方面的各种类似问题。在实现这些研究目标的过程中，我们将利用共同研究者的多样化技能、丰富的研究经验以及建立的合作关系，他们每个人都在开发和应用新型统计方法来研究艾滋病毒预防和治疗问题方面拥有良好的记录。!

DESCRIPTION (provided by applicant): Evaluation of novel approaches to prevent and treat HIV remains a pressing public health priority, particularly in sub-Saharan Africa. The ability to conduct such evaluations effectively requires the development of novel statistical methods capable of addressing the unique complexities of the data available to inform HIV research. This includes both data from population-based surveys, and from randomized controlled trials of prevention and treatment interventions. We propose to pursue three avenues of methodological development to advance this research agenda. First, we will develop methods that use population-based survey data to estimate the potential impact of population circumcision interventions, applying these methods to data from Lesotho. Second, we will develop methods for estimation of treatment effects on combined endpoints comprised of events that are monitored irregularly in a clinical trial population and thus subject to informative interval censoring. The techniques will be developed and illustrated using data from the Tshepo trial in Botswana. Third, we will develop and compare methods to estimate the contributions of specific causal pathways to the effects of randomized HIV prevention interventions. We will apply these methods to data from a randomized controlled trial of diaphragm use in Zimbabwe and South Africa to estimate the effect of diaphragms on HIV transmission, controlling for the unintended effect of diaphragms on condom use. Each specific aim is motivated by a concrete public health question, and we anticipate in each case that the results of the proposed research will provide a valuable applied contribution with the potential for considerable impact. At the same time, the larger goal of each aim is to develop a general set of practical methods with broad applicability to a wide range of similar questions in HIV prevention and treatment. In accomplishing these research goals we will build on the diverse skill set, extensive research experience, and established collaborations of the co-investigators, each of whom has a strong record of developing and applying novel statistical methods to research questions in HIV prevention and treatment. !