Role of Non-pharmacological Pain Treatments in Safe and Effective Opioid Tapering in Chronic Pain

背景：有证据表明长期阿片类药物治疗存在严重不良结局的风险和获益有限 （LTOT）导致VA建议在获益不再时LTOT逐渐减少或停止 超过伤害。然而，LTOT逐渐减少也可能造成伤害的风险。重要性：本研究探讨了 迫切需要明确证明LTOT逐渐减少的风险，并要求进行特定的VA评估， 非药物疼痛治疗，包括补充和综合卫生服务（NPM/CIH）。的 本项目的目标是评估NPM/CIH在安全和临床意义上的作用 减少慢性疼痛退伍军人的LTOT方案。与两个主要问题相关的结果变化 期间-全卫生保健系统（WHS）和COVID-19的实施将得到评估。 创新和影响：与以患者为中心的护理和文化办公室保持合作关系 为了实现转型（OPCC&CT），该研究将扩大正在进行的国家预防机制/CIH评估的范围， 与物质依赖和成瘾有关的结果。与药房福利管理合作 服务的VA药物安全中心（MedSAFE），由新的试点数据通知，我们的团队将是其中之一， 第一个应用一种新的方法来优化LTOT锥形的确定，以改善锥形的分析， 相关成果。该研究将为临床指南提供信息，解决多模式逐渐减少的方法。 具体目标是：（1）描述NPM/CIH在患有LTOT的退伍军人中的访问和使用情况， 考虑实施VHA全保健系统和COVID-19的影响;（2） 比较阿片类药物逐渐减少的有效性和安全性，为退伍军人与LTOT有和没有NPM/CIH;（3） 评估丁丙诺啡对NPM/CIH对结局影响的调节作用。我们假设使用 NPM/CIH将与更高的有效性和安全性相关，并且使用丁丙诺啡将是 与NPM/CIH对这些结果的更积极影响相关。 方法：该项目将确定2016-2020年期间约20万人的回顾性队列 在54家VA机构中接受≥ 30 mg吗啡等效日剂量（MEDD）LTOT的退伍军人。 利用退伍军人健康管理局（VHA）的电子健康记录数据，退伍军人利用 将对VHA和社区内的NPM/CIH进行评估。应用VA开发的新方法 MedSAFE使用公司数据仓库中的VHA电子药房数据，我们将开发模型 阿片类药物的减量使用准实验方法，退伍军人将被“分配”到 NPM/CIH治疗或不治疗的基础上，他们观察到的服务利用。倾向分数匹配将 平衡非随机分配导致的基线差异。在多水平模型中，阿片类药物减量结局 将被建模为NPM/CIH使用的函数。主要减量有效性结局将是 达到处方阿片类药物剂量减少≥基线mg MEDD 50%的退伍军人比例， 在没有恶化的疼痛强度的情况下维持六个月以上。锥形安全性将被测量为 发生任何严重不良事件（SAE）的退伍军人比例，允许逐渐减少所有值， 包括没有逐渐减量和剂量增加。SAE将包括住院、急诊科访视、阿片类药物 过量，新的精神健康障碍，新的阿片类药物或其他物质使用障碍，自杀企图，以及所有- 导致死亡。模型将评估丁丙诺啡治疗阿片类药物对NPM/CIH效应的调节作用 逐渐减少和慢性疼痛。次要模型将评估NPM/CIH对LTOT相关侧的影响 不同年龄、种族/民族和性别的NPM/CIH效应和差异。后续步骤/实施： 业务合作伙伴和退伍军人参与小组将指导对结果的解释， 传播和翻译实践。结果将为支持扩大规模的实施研究提供信息 维持有效的疼痛管理做法，促进安全有效地减少阿片类药物。

Background: Evidence of risks for serious adverse outcomes and limited benefit of long-term opioid therapy (LTOT) have driven VA recommendations for LTOT tapering or discontinuation when benefits no longer outweigh harms. However, LTOT tapering may also pose risks of harm. Significance: The study addresses a critical need for clear demonstration of LTOT tapering risks and a specific VA call for evaluation of nonpharmacological pain treatments including complementary and integrative health services (NPM/CIH). The goals of this project are to assess the role of NPM/CIH use in effecting safe and clinically meaningful reductions in LTOT regimens for Veterans with chronic pain. Changes in outcomes associated with two major periods -- the implementation of the Whole Health System of care (WHS) and COVID-19 – will be assessed. Innovation and Impact: In ongoing partnership with the Office of Patient-Centered Care and Cultural Transformation (OPCC&CT), the study will broaden the scope of ongoing NPM/CIH evaluation to include outcomes related to substance dependence and addiction. Partnering with Pharmacy Benefits Management Services’ VA Center for Medication Safety (MedSAFE), informed by new pilot data, our team will be one of the first to apply a novel method to optimize determination of LTOT tapering to improve analyses of tapering- related outcomes. The study will inform clinical guidelines addressing multimodal approaches to tapering. Specific Aims are to (1) Characterize NPM/CIH access and utilization among Veterans with LTOT, considering the impact of implementation of the VHA Whole Health System of Care and COVID-19; (2) Compare the effectiveness and safety of opioid tapering for Veterans with LTOT with and without NPM/CIH; (3) Assess the moderating effect of buprenorphine on NPM/CIH effects on outcomes. We hypothesize that use of NPM/CIH will be associated with higher rates of effectiveness and safety, and that use of buprenorphine will be associated with more positive effects of NPM/CIH on these outcomes. Methodology: The project will identify a retrospective cohort between 2016-2020 of approximately 200,000 Veterans receiving LTOT at ≥ 30 mg morphine equivalent daily dose (MEDD) across 54 VA facilities. Leveraging Veterans Health Administration (VHA) electronic health record data, Veterans’ utilization of NPM/CIH within VHA and in the community will be assessed. Applying a novel method developed by VA MedSAFE using VHA electronic pharmacy data within the Corporate Data Warehouse, we will develop models of opioid tapering within the target period. Using quasi-experimental methods, Veterans will be “assigned” to NPM/CIH treatment or no treatment based on their observed service utilization. Propensity score matching will balance baseline differences due to nonrandom assignment. In multilevel models, opioid tapering outcomes will be modeled as a function of NPM/CIH use. The primary tapering effectiveness outcome will be the proportion of Veterans achieving a reduction in prescribed opioid dose of ≥50% of baseline mg MEDD, maintained over six months in the absence of worsened pain intensity. Tapering safety will be measured as the proportion of Veterans experiencing any serious adverse event (SAE), allowing tapering to take all values, including no taper and dose increases. SAE will include hospitalization, emergency department visit, opioid overdose, new mental health disorder, new opioid or other substance use disorder, suicide attempt, and all- cause mortality. Models will assess moderation of NPM/CIH effects by buprenorphine treatment for opioid tapering and for chronic pain. Secondary models will assess the effect of NPM/CIH on LTOT-related side effects and differences in NPM/CIH effect by age, race/ethnicity and gender. Next Steps/Implementation: Operational partners and a Veteran engagement panel will guide interpretation of results and promote dissemination and translation to practice. Results will inform an implementation study to support the scale-up and sustainment of effective practices for pain management and facilitating safe and effective opioid reduction.