Estimating the Effect of Low-Dose Aspirin on Fetal Loss in a Trial with Non-Compliance

项目摘要/摘要 流产是最常见的妊娠结局，可能会产生持久的心理影响 即使在一个健康的孩子出生后，也要坚持下去。现有的为数不多的治疗选择是昂贵的，潜在的 侵袭性的，降低生活质量，或与不良后遗症相关。阿司匹林是一种耐受性很好的过度- 这种非处方药，但对其对复发高危妇女促进活产的影响知之甚少 流产。阿司匹林对妊娠和生殖的影响(AGER)研究是一项随机试验 小剂量阿司匹林预防流产和促进活产的作用。虽然研究发现了一小部分 阿司匹林对活产的影响，解释这些结果因几个挑战而复杂化，这些挑战通常会影响 随机试验。这些包括研究参与者没有遵守分配的治疗，错误的- 测量阿司匹林的暴露，并在不具有代表性的样本中研究阿司匹林的影响 感兴趣的人群。其中每一项都有可能导致关于治疗效果的错误推断 更普遍的人群。我们将使用适当的工具重新分析来自这项前瞻性队列研究的数据 解释了这些并发症中的每一种。具体地说，我们将(目标1)估计每日低点的影响 阿司匹林对流产和成功分娩的影响；(目标2)更正这些潜在的影响估计 测量误差；以及(目标3)将这些效应估计推广到具有临床代表性的人群。 这项工作的成功完成将填补人们对阿司匹林预防疾病益处的认识上的重大空白 流产和促进活产。我们具有成本效益、高效和方法创新的项目将 帮助指导临床医生和公共卫生从业者就此做出明智的决定 廉价的预防策略。此外，通过开发和传播我们项目的方法和 软件程序，我们将促进我们最先进的分析技术的广泛使用 用于随机试验分析中的常见问题。因此，这个项目的影响将是广泛的， 并将使任何实质性领域的研究人员能够充分解决困扰几乎所有试验的关键问题 生物医学和社会科学。

Project Summary/Abstract Miscarriage is the most common pregnancy outcome, and can have lasting psychological implications that persist even after the birth of a healthy child. The few treatment options that exist are costly, potentially invasive, undermine quality of life, or are associated with adverse sequelae. Aspirin is a well-tolerated over- the-counter drug, but little is known about its effects on promoting live birth in women at high risk of recurrent miscarriage. The Effects of Aspirin in Gestation and Reproduction (EAGeR) study was a randomized trial of the effect of low-dose aspirin on preventing miscarriage and promoting live birth. While the study found a small effect of aspirin on live birth, interpreting these results is complicated by several challenges that routinely affect randomized trials. These include failure of study participants to comply with the assigned treatment, mis- measurement of exposure to aspirin, and studying aspirin effects in a sample that is not representative of the population of interest. Each of these creates the potential for incorrect inferences regarding treatment effects in more general populations. We will reanalyze data from this prospective cohort study using tools that properly account for each of these complications. Specifically, we will (Aim 1) estimate the effect of taking daily low dose aspirin on miscarriage and successful live birth; (Aim 2) correct these effects estimates for potential measurement error; and (Aim 3) generalize these effect estimates to clinically representative populations. Successful completion of this work will fill critical gaps in knowledge about the benefits of aspirin in preventing miscarriage and promoting live birth. Our cost-effective, efficient, and methodologically innovative project will help guide clinicians and public health practitioners in making informed decisions about this simple and inexpensive preventive strategy. Furthermore, by developing and disseminating our project's methods and software programs, we will facilitate the widespread use of our state-of-the-art analytic techniques to account for common problems in the analysis of randomized trials. Consequently, the impact of this project will be wide, and will enable researchers in any substantive area to fully address critical issues that plague nearly all trials in the biomedical and social sciences.