Assessing real-world evidence of the effects of opioid analgesic tapering on substance-related problems

评估阿片类镇痛药逐渐减少对物质相关问题影响的现实证据

• 批准号: 10740980
• 负责人: Patrick Donovan Quinn
• 金额: $ 37.4万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10740980
• 关键词: Academy; Adult; Adverse effects; Affect; Black race; COVID-19 pandemic; Clinical; Clinical Practice Guideline; Complement; Consensus; Data; Decision Aid; Decision Making; Dose; Equilibrium; Equity; Ethnic Population; Goals; Guidelines; Healthcare; Heterogeneity; Hispanic; Individual; International; Intervention; Journals; Latino; Literature; Long-Term Effects; Measurement; Measures; Medical; Medicare; Medicine; Mental Health; Methods; Opioid; Opioid Analgesics; Outcome; Overdose; Pain; Pain management; Paper; Patient Care; Patient risk; Patients; Persons; Pharmacoepidemiology; Policies; Published Comment; Recommendation; Reproducibility; Research; Research Design; Risk; Risk Estimate; Safety; Self-Injurious Behavior; Specificity; Subgroup; Substance Use Disorder; Time; United States Department of Veterans Affairs; chronic pain; chronic pain management; design; dosage; evidence base; evidence based guidelines; experience; improved; individual patient; individual variation; innovation; insurance claims; marginalization; non-opioid analgesic; opioid tapering; opioid therapy; opioid use disorder; overdose risk; pain relief; patient safety; population health; prescription opioid; programs; racial population; social

Project Summary/Abstract Against the background of major efforts to alleviate the adverse effects of long-term opioid therapy (LtOT) for chronic pain, there is great concern about the risk of unintended harmful consequences among those tapering opioid dosage or discontinuing LtOT. For this reason, a 2020 National Academy of Medicine discussion paper and multiple other recent commentaries have highlighted the urgent need for real-world evidence regarding the benefits and harms of LtOT tapering. The overall objective of this proposal is to leverage large-scale healthcare data and rigorous pharmacoepidemiologic designs to strengthen the evidence base concerning the extent to which LtOT tapering affects risk of 4 substance-related outcomes: overdose, opioid use disorder (OUD), other substance use disorder (SUD), and intentional overdose/other self-harm. The central hypothesis is that there are minimal adverse effects of tapering compared with maintaining LtOT—and that the effects are limited to certain clinical contexts and subgroups. The proposal’s rationale is that combining design-based and statistical control of confounding with rigor in measurement of LtOT, tapering, and substance-related outcomes is essential to strengthening evidence on LtOT tapering. The project will evaluate its central hypothesis in 2 specific aims: (1) estimate the effects of LtOT tapering on serious substance-related outcomes, and (2) identify patient groups more vulnerable to the estimated effects of LtOT tapering. Both aims will involve the analysis of patients receiving LtOT in nationwide, longitudinal data from commercial and Medicare Advantage healthcare insurance claims. In aim 1, the project will estimate the extent to which LtOT tapering is associated with risk of substance-related outcomes (overdose, OUD, other SUD, and intentional self-harm). The primary analytic approach will be a within-individual design that rules out confounding from all time-stable factors by capitalizing on intra-individual variability over time, complemented with statistical covariates to help account for time-varying confounding. Aim 2 will employ this within-individual approach in subgroups to determine whether tapering-related harms are greater among individuals (a) with longer-duration LtOT, (b) with higher-dose LtOT, (c) experiencing more rapid tapering, (d) with pre-existing SUD or other mental health conditions, or (e) from marginalized (Black or Hispanic/Latino/a) racial and ethnic groups. The innovation of the proposal is in its (a) rigorous research designs to reduce confounding and other biases, (b) consideration of heterogeneity in tapering effects, and (c) interdisciplinary, international research team. The proposal is significant because it will guide harm-benefit calculations and best practices (e.g., tapering rates) for policy, as well as for individual patients. Without this information, tapering recommendations must still be made using evidence that has been repeatedly described as inadequate. Thus, the proposed research has the potential to enhance decision-making to maximize pain relief, safety, and equity in LtOT tapering.

项目概要/摘要 在大力减轻长期阿片类药物治疗（LtOT）不良反应的背景下 对于慢性疼痛，人们非常担心这些人可能会产生意想不到的有害后果 为此，2020 年美国国家医学科学院发布了减少阿片类药物剂量或停止 LtOT 的建议。 讨论文件和最近的许多其他评论都强调了现实世界的迫切需要 有关 LtOT 逐渐减少的好处和危害的证据 该提案的总体目标是 利用大规模医疗保健数据和严格的药物流行病学设计来加强证据 关于 LtOT 逐渐减少对 4 种物质相关结果风险的影响程度的基础：用药过量、 阿片类药物使用障碍 (OUD)、其他物质使用障碍 (SUD) 和故意过量/其他自残。 中心假设是，与维持 LtOT 相比，逐渐减少的不利影响最小，并且 该提案的基本原理是，效果仅限于某些临床背景和亚组。 基于设计和统计的控制，对 LtOT、逐渐变细和测量中的严格性混杂进行控制 物质相关的结果对于加强 LtOT 逐渐减少的证据至关重要，该项目将进行评估。 其中心假设有两个具体目标：(1) 估计 LtOT 逐渐减少对严重物质相关的影响 (2) 确定更容易受到 LtOT 逐渐减少的估计影响的患者群体。 将涉及对全国范围内接受 LtOT 的患者进行分析，纵向数据来自商业和 在目标 1 中，Medicare Advantage 医疗保险索赔将估计 LtOT 的程度。 逐渐减少与物质相关结果的风险相关（过量、OUD、其他 SUD 和故意） 主要的分析方法将是排除所有人的混淆的个体内部设计。 时间稳定因素，利用个体内部随时间的变化，并辅以统计数据 协变量来帮助解释随时间变化的混杂因素，目标 2 将采用这种个体内部方法。 亚组以确定与逐渐减少相关的危害是否在持续时间较长的个体中更大 LtOT，(b) 使用较高剂量的 LtOT，(c) 经历更快速的减量，(d) 使用预先存在的 SUD 或其他 心理健康问题，或 (e) 来自边缘化（黑人或西班牙裔/拉丁裔/a）种族和族裔群体。 该提案的创新之处在于（a）严格的研究设计，以减少混杂和其他偏见，（b） 考虑逐渐减少效应的异质性，以及 (c) 跨学科的国际研究团队。 该提案意义重大，因为它将指导危害效益计算和最佳实践（例如逐渐减少率） 对于政策以及个别患者来说，如果没有这些信息，仍必须提出逐渐减少的建议。 因此，所提出的研究具有被反复描述为不充分的证据。 增强决策的潜力，以最大限度地减轻 LtOT 逐渐减少的疼痛、安全性和公平性。