New methods for the design and evaluation of large HIV prevention interventions

描述（由申请人提供）：新发现的预防艾滋病毒的有效工具的出现带来了新的挑战和对新范例的需求：当我们有证据表明单独使用艾滋病毒预防工具可以减少艾滋病毒传播时，我们如何以道德的方式评估组合使用艾滋病毒预防工具的影响？我们如何推出有效的策略，但在实际环境中大规模评估其有效性和成本效益？目前正在进行的四个主要艾滋病毒预防干预措施之间的强有力合作-包括哈佛大学的博茨瓦纳社区预防项目和Familia Salama PMTCT研究，范德比尔特大学和帝国理工学院的PopART项目，以及非洲中心的治疗预防试验，我们的建议，题为“设计和评估大型艾滋病毒预防干预措施的新方法”将解决设计和分析这些大型艾滋病毒预防干预项目的可用方法中的关键差距。在与这些项目的主要研究者和其他关键人员（其中三人是本提案的共同研究者）进行了广泛的对话后，我们确定了我们的具体目标：1)开发和验证新的网络方法，以改进大型联合预防临床试验的评估2)开发先进的统计方法，以改进大规模艾滋病毒预防研究的设计和评估。3)加强预防试验设计，以调整因随访缺失而导致的偏倚，并评估传染性和间接影响。4)解开并评估包含“一揽子”的特定干预措施的效果，如哈佛-博茨瓦纳和HPTN 061/PopART试验

DESCRIPTION (provided by applicant): The advent of newly discovered efficacious tools for the prevention of HIV creates a new challenge and the need for new paradigms: How do we assess the impact of combinations of HIV prevention tools in ethical ways, when we have evidence that individually they work to reduce HIV transmission? How do we roll out efficacious strategies, but assess their effectiveness and cost-effectiveness in real-world settings at scale? In a powerful collaboration between four of the major HIV preventive interventions currently underway - including Harvard's Botswana Community Prevention Project and Familia Salama study of PMTCT, Vanderbilt and Imperial's PopART project, and the Africa Centre's Treatment as Prevention trial, our proposal, entitled "New methods for the design and evaluation of large HIV prevention interventions" will address key gaps in the available methodologies for the design and analysis of these large- scale HIV preventive intervention projects. After extensive dialogue with the Principal Investigators and other key personnel on these projects (three of whom are Co-investigators of this proposal), we have identified our specific aims as: 1) To develop and validate novel network methods to improve the evaluation of large combination prevention clinical trials 2) To develop advanced statistical methods to improve the design and evaluation of large- scale HIV prevention studies. 3) To augment prevention trial designs to adjust for bias due to loss to follow-up and to assess infectiousness and indirect effects. 4) To disentangle and evaluate the effects of specific interventions that comprise a 'package' as in the Harvard-Botswana and HPTN 061/PopART trials