Statistical Designs and Methods for Partially Controlled HIV/AIDS Studies

部分对照艾滋病毒/艾滋病研究的统计设计和方法

• 批准号: 7874586
• 负责人: CONSTANTINE E FRANGAKIS
• 金额: $ 32.62万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-15 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7874586
• 关键词: AIDS/HIV problem; Accounting; Address; Affect; Africa; Baltimore; Cellular Immunity; Child; Clinical; Controlled Study; Data; Diagnosis; Evaluation; Event; HIV; HIV Infections; HIV vaccine; Health; Infection; Letters; Location; Methods; Monitor; Mothers; Nature; Needle-Exchange Programs; Outcome; Participant; Persons; Phase; Population; Population Programs; Prevention; Property; Public Health; Publications; Randomized; Research Personnel; Risk; Selection Bias; Site; Site Visit; Statistical Methods; Stratification; Testing; Time; Vaccinated; Vaccination; Vaccines; Viral Load result; Viral load measurement; Work; base; design; efficacy trial; experience; improved; programs; success; transmission process; treatment effect; treatment program; treatment site; vaccine efficacy; AIDS/HIV problem; Accounting; Address; Affect; Africa; Baltimore; Cellular Immunity; Child; Clinical; Controlled Study; Data; Diagnosis; Evaluation; Event; HIV; HIV Infections; HIV vaccine; Health; Infection; Letters; Location; Methods; Monitor; Mothers; Nature; Needle-Exchange Programs; Outcome; Participant; Persons; Phase; Population; Population Programs; Prevention; Property; Public Health; Publications; Randomized; Research Personnel; Risk; Selection Bias; Site; Site Visit; Statistical Methods; Stratification; Testing; Time; Vaccinated; Vaccination; Vaccines; Viral Load result; Viral load measurement; Work; base; design; efficacy trial; experience; improved; programs; success; transmission process; treatment effect; treatment program; treatment site; vaccine efficacy

DESCRIPTION (provided by applicant): An important objective of biomedical studies of HIV/AIDS is to estimate the effect of factors on HIV/AIDS outcomes. Although there has been a rich list of methods of analysis that are appropriate if such factors are assumed controlled, there is important need for designs and methods to validly estimate the effect of, and to maximize the benefit from factors that cannot be directly controlled. In this proposal, we will develop designs and methods to better estimate and to maximize the benefit that uncontrolled factors have on a population. The proposed methods will build on preliminary work we have conducted using the framework of "principal stratification". The success of that work increases the potential impact of this proposal. The proposed methods are developed for two broad aims, and are motivated by needle exchange programs in the US, HIV treatment administration in East Africa, and HIV vaccine efficacy trials. (Aim 1)Develop designs to maximize the treatment benefit for participants in studies that control the location of sites that offer treatments, but do not directly control who gets treatment or who provides outcomes. Such a situation arises with sites offering needle exchange programs in the US, and with sites operating HIV treatment programs in the developing world. We have previously developed methods to estimate the treatment effect on a population given a design. We now propose new methods to find designs that maximize both, the treatment effect on a population, as well as the information needed to periodically monitor that effect. Our methods are motivated by and will be applied to designate placements that maximize the benefit of the Baltimore Needle Exchange Program, and of the PEPFAR HIV programs in East Africa. (Aim 2)Develop statistical methods to better evaluate the effect of a treatment on outcomes which are defined only in an uncontrolled subset of participants selected after randomization. Such a situation arises in HIV vaccine trials when assessing the effect of a vaccine on outcomes (e.g., viral load) that are defined only on the subsets who are infected with HIV post-randomization. Vaccines that are infected with HIV can be different from those who are infected without the putative effect of vaccine on infection risk. We propose more valid methods to estimate the effects of HIV vaccines on longitudinal post-infection outcomes. Our methods are motivated and will be applied to the first cell-mediated immunity HIV vaccine trial (Step trial), and to the Mashi trial on mother-to-child HIV transmission.

描述（由申请人提供）：艾滋病毒/艾滋病生物医学研究的一个重要目标是估计因素对艾滋病毒/艾滋病结果的影响。尽管有很多分析方法列表，如果假定这些因素被控制，则需要进行设计和方法，以便有效地估计无法直接控制的因素的益处，并最大程度地估算益处。在此提案中，我们将开发设计和方法，以更好地估计并最大程度地提高不受控制的因素对人群的收益。提出的方法将基于我们使用“主要分层”框架进行的初步工作。这项工作的成功增加了该提议的潜在影响。提出的方法是针对两个广泛的目标开发的，是由美国的针交换计划，东非的HIV治疗管理和HIV疫苗疗效试验的动机。 （目标1）开发设计，以最大程度地利用控制提供治疗的地点但不直接控制谁获得治疗或提供结果的研究的研究中的参与者的治疗益处。这种情况是在美国提供针头交换计划的站点以及发展中国家的艾滋病毒治疗计划的站点。我们以前已经开发了估计对设计人群的治疗效果的方法。现在，我们提出了新的方法，以找到最大化的设计，即对人群的治疗效果以及定期监视该效果所需的信息。我们的方法是由动机，并将应用于指定位置，以最大程度地提高巴尔的摩针交换计划的好处以及东非的Pepfar HIV计划。 （目标2）开发统计方法，以更好地评估治疗对结果的影响，这些结果仅在随机分组后选择的参与者的不受控制的子集中定义。当评估疫苗对仅在感染HIV后随机后感染的亚种上定义的结果（例如病毒载量）的影响时，这种情况是在HIV疫苗试验中出现的。感染艾滋病毒的疫苗可能与那些没有疫苗对感染风险的没有假定影响的感染者不同。我们提出了更有效的方法来估计HIV疫苗对纵向感染后结果的影响。我们的方法是动机的，并将应用于第一个细胞介导的免疫HIV疫苗试验（Step Five），以及对母亲到孩子HIV传播的Mashi试验。