Pooling HIV Cohorts to Inform Clinical Decision

描述(由申请人提供)：我们建议汇集来自五项艾滋病毒队列研究的数据，以回答艾滋病毒感染患者管理中的关键问题：何时启动高效抗逆转录病毒疗法(HAART)？哪些HAART方案作为初始治疗效果更好？以及何时切换到另一种HAART方案？观察性队列研究适合于这种分析，因为它们比随机试验更具成本效益，使用比随机试验更少的限制性资格标准，并且在适当分析时，提供了与随机试验所获得的接近的HAART疗效估计。然而，由于样本量的考虑，任何一个单独的队列都不太可能足以获得稳定的估计。因此，我们汇集了西欧和北美正在进行的五项前瞻性队列研究的数据：退伍军人老龄化队列研究(美国)、瑞士艾滋病毒队列研究(瑞士)、法国医院数据库艾滋病毒研究(法国)、Gemes(西班牙)和Piscis(西班牙加泰罗尼亚和巴利阿里群岛)。这些研究总共招募了超过14万名艾滋病毒感染患者。我们将以一种尽可能接近随机试验设计的方式使用来自几个观察性队列的数据。然后，我们将应用逆概率加权、g-估计和参数g-公式(Robins和合作者在过去20年中开发的方法)。这些方法不仅在理论上有效地解决了这些问题，而且在应用于观测数据时也成功地复制了先前随机试验的结果。我们的研究将为循证指南和临床试验的规划提供信息。此外，建议的这一先进方法的成功应用将促进美国和欧洲领先的艾滋病毒观察性研究小组在因果建模方面的理解和培训。

DESCRIPTION (provided by applicant): We propose to pool data from five HIV cohort studies to answer pivotal questions in the management of patients with HIV infection: when to initiate Highly Active Antiretroviral Therapy (HAART)?, which HAART regimes work better as initial treatment?, and when to switch to another HAART regime? Observational cohort studies are appropriate for this analyses as they are more cost-efficient than randomized trials, use less restrictive eligibility criteria than randomized trials, and, when analyzed appropriately analyzed have provided estimates of the efficacy of HAART close to those obtained from the randomized trials. Nevertheless, because of sample size considerations, it is unlikely that any single cohort will be sufficient to obtain stable estimates. We therefore pool data from five ongoing prospective cohort studies in Western Europe and North America: the Veterans Aging Cohort Study (USA), the Swiss HIV Cohort Study (Switzerland), the French Hospital Database HIV Study (France), GEMES (Spain), and PISCIS (Catalonia and Balearic Islands, Spain). Together, these studies have recruited more than 140,000 HIV infected patients. We will use the data from several observational cohorts in a way that mimics the design of randomized trials as closely as possible. We will then apply inverse probability weighting, g-estimation, and the parametric g- formula (methods developed by Robins and collaborators over the last two decades). These methods are not only theoretically valid to address these questions but have also successfully reproduced results from previous randomized trials when applied to observational data. Our study will inform evidence-based guidelines, and the planning of clinical trials. In addition, the successful application of this advanced methodology as proposed will facilitate understanding and training in causal modeling across leading HIV observational research groups in the United States and Europe.