Pharmacoepidemiologic Studies of Prescription Opioid Analgesic Risks

处方阿片类镇痛风险的药物流行病学研究

• 批准号: 9757726
• 负责人: Patrick Donovan Quinn
• 金额: $ 24.66万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9757726
• 关键词: Accidents; Adverse effects; Adverse event; Alcohol or Other Drugs use; Area; Attenuated; Behavioral; Cessation of life; Clinical; Collaborations; Complement; Data; Data Set; Decision Making; Depression and Suicide; Educational workshop; Epidemiology; Experimental Designs; Future; Goals; Health; Individual; International; Journals; Link; Literature; Long-Term Effects; Medical; Mental Depression; Methods; Mood Disorders; Morbidity - disease rate; Observational Study; Onset of illness; Opioid; Opioid Analgesics; Outcome; Pain; Pain Research; Pain management; Patients; Peer Review; Persons; Pharmaceutical Preparations; Pharmacoepidemiology; Policies; Population; Process; Published Comment; Randomized Controlled Trials; Reporting; Research; Risk; Risk Behaviors; Risk Estimate; Role; Sales; Sample Size; Science; Selection Bias; Source; Substance Use Disorder; Techniques; Testing; Time; Training; Uncertainty; United States National Institutes of Health; base; clinical pain; design; experience; experimental study; follow-up; individual patient; insurance claims; mortality; opioid epidemic; overdose death; population based; prescription opioid; programs; public health priorities; public health relevance; responsible research conduct; skills; social; socioeconomic disadvantage; suicidal behavior; suicidal risk; translational pipeline; trend; vehicular accident

 DESCRIPTION (provided by applicant): Recent increases in opioid analgesic prescribing in the US and worldwide have coincided with increases in opioid-related morbidity and mortality. As described in a 2015 NIH workshop report and in multiple commentaries in peer-reviewed health journals, however, the exact harms of prescription opioid analgesics- and their precise role in the ongoing opioid epidemic-remain unclear. This uncertainty has been driven by the limited sample sizes and follow-up durations of randomized, controlled trials, as well as the challenge of ruling out biased selection and other confounding in observational studies. Notably, patients who receive prescription opioids may also be more likely to have pre-existing conditions such as substance use disorders. This process is referred to as "adverse selection," and it suggests that prior estimates of opioid harms from some observational studies may have been artificially inflated. The overall objective of the proposed research is, therefore, to use advance pharmacoepidemiologic approaches to determine the extent to which prescribed opioids have behavioral harms. In particular, the proposed studies will estimate the risks of prescribed opioids for substance use disorders, motor vehicle accidents, depression, and suicidal behavior, each of which has been identified in prior literature as a potential opioid harm. In 2 population-level datasets-including 1.9 million opioid recipients drawn from the whole Swedish population and 26 million opioid recipients drawn from US insurance claims-these studies will evaluate the central hypothesis that prescribed opioids are associated with behavioral harms, which would be consistent with true adverse effects. First, the proposed research will examine the extent to which patients receive prescription opioids more frequently in the presence of pre- existing substance use disorders, mood disorders, and other social and behavioral factors. Having identified these potential confounds, analyses will subsequently estimate risk associations between opioid prescriptions and both short-term and long-term behavioral harms. Specifically, analyses will use within-person comparisons, which implicitly rule out all sources of time-invariant confounding, and time-varying statistical covariates, which explicitly rule out sources o time-varying confounding. The rationale for this approach is that the combination of within-person analyses, time-varying covariates, and data from two populations will help generate more accurate estimates of the adverse effects of prescribed opioids. The proposed research will be complemented with training in (a) pharmacoepidemiology and other quasi-experimental research, (b) clinical pain research, (c) collaborative science, and (d) the responsible conduct of research. Upon the completion of the proposed activities, the applicant is expected to have reached the long-term goal of establishing an independent program researching the causes and consequences of opioid and other substance use.

 描述（由申请人提供）：最近美国和全球阿片类镇痛药处方的增加与阿片类相关发病率和死亡率的增加相一致。然而，正如2015年NIH研讨会报告和同行评议的健康期刊上的多篇评论所述，处方阿片类镇痛药的确切危害-以及它们在持续的阿片类镇痛药中的确切作用-仍然不清楚。这种不确定性是由于随机对照试验的样本量和随访时间有限，以及在观察性研究中排除偏倚选择和其他混杂因素的挑战。值得注意的是，接受处方阿片类药物的患者也更有可能患有预先存在的疾病，如物质使用障碍。这一过程被称为“逆向选择”，它表明，一些观察性研究对阿片类药物危害的先前估计可能被人为夸大了。因此，拟议研究的总体目标是使用先进的药物流行病学方法来确定处方阿片类药物对行为危害的程度。特别是，拟议的研究将估计处方阿片类药物的风险， 用于物质使用障碍、机动车事故、抑郁症和自杀行为，其中每一种都在先前文献中被确定为潜在的阿片类药物危害。在2个人群水平的队列中-包括来自整个瑞典人口的190万阿片类药物接受者和来自美国保险索赔的2600万阿片类药物接受者-这些研究将评估中心假设，即处方阿片类药物与行为危害相关，这与真正的不良反应一致。首先，拟议的研究将检查患者在存在预先存在的物质使用障碍，情绪障碍以及其他社会和行为因素的情况下更频繁地接受处方阿片类药物的程度。在确定了这些潜在的混淆后，分析将随后估计阿片类药物处方与短期和长期行为危害之间的风险关联。具体而言，分析将使用人内比较（隐含排除所有时不变混杂源）和时变统计协变量（明确排除时变混杂源）。这种方法的基本原理是，将人内分析、时变协变量和来自两个人群的数据相结合，将有助于更准确地估计处方阿片类药物的不良反应。拟议的研究将辅以以下方面的培训：（a）药物流行病学和其他准实验研究，（B）临床疼痛研究，（c）协作科学，以及（d）负责任地开展 research.在完成拟议的活动后，申请人预计将达到建立一个研究阿片类药物和其他物质使用的原因和后果的独立项目的长期目标。