Assessing the Safety and Effectiveness of Opioid Tapering in Large Health Systems

项目摘要 美国正处于阿片类药物流行病的快速发展之中，阿片类药物导致20多万人死亡。 从1999年开始服用过量止痛药2016年，美国疾病控制和预防中心发布了指导方针 阿片类药物治疗慢性疼痛的管理。这些指导方针强调， 处方高剂量阿片类药物治疗或有其他过量风险因素的个人。虽然医生 越来越多地减少或停止（逐渐减少）患者处方的慢性阿片类药物治疗， 缺乏对逐渐减量做法的有效性和安全性的支持。而逐渐减少的阿片类药物代表着 合理的方法来减少过量的风险，也有人担心逐渐减少阿片类药物可能导致 增加疼痛和戒断，促使一些人寻求非法阿片类药物，如海洛因，矛盾的是， 增加了他们服药过量的风险 本项目的总体目标是进行纵向队列研究，以确定有效性和 在大型卫生系统中阿片类药物逐渐减少的安全性。我们将利用数据系统（阿片类药物安全途径 Datalink [POSD]）包含有关农村和城市地区超过250万人的关联数据 科罗拉多和威斯康星州。使用POSD数据系统，我们将在一个队列中检查阿片类药物减量实践 从2012年到2020年，大约有48，000名患者接受了慢性阿片类药物治疗。我们将采用新的 分析技术，以确定不同的减量做法，如逐渐减少剂量，快速减少剂量， 停药后重新开始给药和持续停药。然后我们将决定 哪些患者和提供者因素和行为与阿片类药物逐渐减少有关。在队列中， 将通过比较逐渐减量的临床重要结果来检查有效性和安全性 实践结局将包括用药过量、自杀、阿片类药物使用障碍和对疼痛的医疗保健利用， 戒断最后，我们将开发和应用新的方法，以尽量减少从损失到后续行动的偏见， 暴露和结局的错误分类，包括定量偏倚分析、概率偏倚分析， 和倾向分数。 我们的研究结果将有可能影响阿片类药物管理的国家临床指南。我们 拟议的研究方法也代表了如何严格评估重要阿片类药物的新范式。 处方和物质使用结果使用复杂的卫生服务数据。

PROJECT ABSTRACT The United States is amidst a rapidly evolving opioid epidemic, with more than 200,000 deaths from opioid pain reliever overdoses since 1999. In 2016, the Centers for Disease Control and Prevention issued guidelines on the management of opioid therapy in chronic pain. These guidelines emphasized tapering opioids among individuals prescribed high-dose opioid therapy or with other overdose risk factors. While physicians are increasingly reducing or discontinuing (tapering) patients prescribed chronic opioid therapy, evidence to support the effectiveness and safety of tapering practices is lacking. While tapering opioids represents a reasonable approach to reduce the risk of overdose, there are also concerns that tapering opioids may lead to increased pain and withdrawal, prompting some individuals to seek illicit opioids such as heroin, paradoxically increasing their risk for overdose. The overall goal of this project is to conduct a longitudinal cohort study to determine the effectiveness and safety of opioid tapering in large health systems. We will leverage a data system (Pathways to Opioid Safety Datalink [POSD]) that contains linked data on more than 2.5 million people in rural and urban areas in Colorado and Wisconsin. Using the POSD data system, we will examine opioid tapering practices in a cohort of approximately 48,000 patients prescribed chronic opioid therapy from 2012 to 2020. We will employ novel analytic techniques to identify distinct tapering practices, such as gradual dose reduction, rapid dose reduction, dose discontinuation followed by re-initiation, and sustained dose discontinuation. We will then determine which patient and provider factors and behaviors are associated with opioid tapering. In the cohort, effectiveness and safety will be examined by comparing clinically important outcomes across tapering practices. Outcomes will include overdose, suicide, opioid use disorder, and health care utilization for pain and withdrawal. Lastly, we will develop and apply novel methods to minimize bias from loss to follow-up and misclassification of exposure and outcomes, including quantitative bias analysis, probabilistic bias analysis, and propensity scores. Our findings will have the potential to influence national clinical guidelines on opioid management. Our proposed research approach also represents a new paradigm for how to rigorously assess important opioid prescribing and substance use outcomes using complex health services data.