Antidepressant Treatment and Suicidality: Biostatistical/Methodological Solutions

描述（由申请人提供）：本提案的目的是开发、测试和应用新的统计设计和分析方法，可用于识别低基础率药物不良事件（AE）相互作用。这些新方法将被广泛应用于现有的非实验数据集，以检验SSRIs与自杀意念、企图和完成之间的关系。我们设计了这个研究项目，作为生物统计学家、研究精神病学家和临床医生、经济学家和药物流行病学家之间的整体合作，与大型生态和电子患者数据库一起工作，这些数据库涵盖了抗抑郁药使用变化巨大的年份。第一套目标将导致发展新的生物统计方法，以便从自发报告和电子病历数据库中进行推论。具体来说，我们将1。利用自发（SRS）和主动报告系统（ARS）开发新的统计设计和分析，以识别药物ae相互作用；2. 发展生物统计学方法，以解决电子病历数据库中的选择和报告偏差；3. 开发大规模药物ae筛选的统计方法。第二组目标是将这些方法应用到现有的大规模数据库中，以检验抗抑郁药在不同人群中自杀行为中的作用。数据集的范围从自发报告系统（MedWatch）到电子病历数据库（例如VA、PHARMetrics、Kaiser和PHARMO、Indian Health Service），再到随机临床试验（rct）信息的综合。本提案中的工作将由一个研究国家和国际药物安全问题的研究联盟进行。多学科组包括统计领域(博士。Gibbons, （PI), Brown (co-Pi), Bhaumik, Duan, Hur, Marcus，撒哈拉），从成人、儿童和遗传角度看精神病学（Brent, Mann, Reynolds, Tsuang），卫生经济学/计量经济学（Meltzer, Heckman），儿科学（Leslie）和药物流行病学（Valuck）。与退伍军人管理局（坎宁安、瓦伦斯坦）、凯撒医疗机构（克拉克、古利昂）、PHARMO（埃尔肯斯）和印第安人医疗服务机构（佩雷斯）的合作是该提议的一个组成部分。

DESCRIPTION (provided by applicant): The purpose of this proposal is to develop, test, and apply new statistical design and analytical methodologies that can be used to identify low base rate drug - adverse event (AE) interactions. These new methods will then be applied to a wide range of existing non-experimental datasets to examine the relationship between SSRIs and suicide ideation, attempts, and completion. We have designed this research project as an integral collaboration between biostatisticians, research psychiatrists and clinicians, economists, and pharmacoepidemiologists, working with large ecological and electronic patient databases covering years where antidepressant use is varying dramatically. The first set of aims will lead to the development of new biostatistical methods for making inferences from spontaneous reporting and electronic medical record databases. Specifically, we will 1. develop new statistical designs and analyses for identifying drug-AE interactions using both spontaneous (SRS) and active reporting systems (ARS); 2. develop biostatistical methods to address selection and reporting bias in electronic medical record databases; 3. develop statistical methods for large-scale drug-AE screening. The second set of aims involves the critical application of these methods to existing large scale databases in order to examine the role of antidepressants in suicidality among different populations. The datasets range from the spontaneous reporting system (MedWatch), to electronic medical record databases (e.g., VA, PHARMetrics, Kaiser, and PHARMO, Indian Health Service), to the synthesis of information from randomized clinical trials (RCTs). The work in this proposal will be carried out by a research consortium that will study national and international drug safety issues. The multidisciplinary group includes the areas of statistics (Drs. Gibbons, (PI), Brown (co-Pi), Bhaumik, Duan, Hur, Marcus, SahaRay), psychiatry from adult, child, and genetic perspectives (Brent, Mann, Reynolds, Tsuang), health economics/econometrics (Meltzer, Heckman), pediatrics (Leslie), and pharmacoepidemiology (Valuck). Collaboration with members of the VA (Cunningham, Valenstein), Kaiser Permanente (Clarke, Gullion), PHARMO (Erkens) and the Indian Health Service (Perez) is an integral part of the proposal.