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

项目总结/摘要 流产是最常见的怀孕结果，并可能产生持久的心理影响， 即使在一个健康的孩子出生后也会持续存在。现有的少数治疗方案是昂贵的，潜在的 侵入性、破坏生活质量或与不良后遗症相关。阿司匹林是一种耐受性良好的过度- 这种非处方药，但很少有人知道它对促进复发性高风险妇女活产的影响。 流产阿司匹林对妊娠和生殖的影响（EAGeR）研究是一项随机试验， 小剂量阿司匹林对保胎促活产作用虽然研究发现， 阿司匹林对活产的影响，解释这些结果是复杂的几个挑战， 随机试验这些包括研究参与者未能遵守分配的治疗，错误- 测量暴露于阿司匹林，并研究阿司匹林的影响，在一个样本，这是不代表的， 感兴趣的人群。其中每一个都可能导致对治疗效果的错误推断， 更一般的人群。我们将使用适当的工具重新分析这项前瞻性队列研究的数据， 这些并发症的原因具体来说，我们将（目标1）估计采取每日低点的效果 剂量阿司匹林流产和成功的活产;（目的2）纠正这些影响估计的潜在 测量误差;和（目标3）将这些效应估计推广到临床代表性人群。 这项工作的成功完成将填补关于阿司匹林在预防糖尿病方面的益处的知识空白。 流产和促进活产。我们的成本效益高，效率高，方法创新的项目将 帮助指导临床医生和公共卫生从业人员做出明智的决定， 廉价的预防战略。此外，通过开发和传播我们项目的方法， 软件程序，我们将促进我们的国家的最先进的分析技术的广泛使用，以帐户 随机试验分析中的常见问题。因此，该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.