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

基本信息

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
项目类别：
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

项目摘要

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）：然而，正如 2015 年 NIH 研讨会报告和同行评审健康期刊的多篇评论所述，最近美国和世界范围内阿片类镇痛药处方的增加与阿片类药物相关发病率和死亡率的增加同时发生。处方阿片类镇痛药的确切危害及其在持续的阿片类药物流行中的确切作用仍不清楚，这种不确定性是由有限的样本量和随访时间造成的。随机对照试验，以及排除观察性研究中的偏见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可能更有可能患有物质使用障碍等已有疾病。被视为“逆向选择”，并且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。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的程度。有特别是，拟议的研究将评估处方阿片类药物的风险。药物使用障碍、机动车事故、抑郁症和自杀行为，这些行为在之前的文献中都被确定为潜在的阿片类药物危害，在 2 个人口层面的数据集中，其中包括来自整个瑞典人口的 190 万阿片类药物接受者和 26 名阿片类药物使用者。来自美国保险索赔的百万阿片类药物接受者——这些研究将评估处方阿片类药物与行为危害相关的中心假设，这与真实的不良反应一致。首先，拟议的研究将检查患者更多地接受处方阿片类药物的程度。经常在确定这些潜在的混杂因素后，分析将随后评估阿片类药物处方与短期和长期行为危害之间的风险关联。使用人内比较，隐式排除所有时不变混杂因素的来源，以及时变统计协变量，明确排除时变混杂因素的来源。这种方法的基本原理是结合人内分析。 ,时变协变量和来自两个人群的数据将有助于对处方阿片类药物的副作用进行更准确的估计。拟议的研究将得到以下方面的培训的补充：（a）药物流行病学和其他准实验研究，（b）临床疼痛。研究，(c) 合作科学，以及 (d) 负责任的行为研究完成后，预计申请人将达到建立一个独立项目来研究阿片类药物和其他物质使用的原因和后果的长期目标。