Extended study of a long-term opioid therapy cohort: trajectories in pain care and patient-centered outcomes

背景：针对长期阿片类药物相关的严重危害和适度获益的证据， 2016年疾病控制和预防中心（CDC）指南和2017年LTOT指南 退伍军人事务部（VA）和国防部（DoD）的指导方针建议 限制阿片类药物处方的频率、强度和持续时间。对于LTOT患者，这些指南 如果益处不明显大于危害，建议逐渐减少剂量或停止。VA 实施指南建议的举措在实践中增加了阿片类药物的减少， LTOT的患病率，但对患者的影响尚不清楚。需要进行研究以了解长期影响 LTOT减少或停止对患者的影响，以及不同的治疗方法如何影响结果。 意义/影响：减少阿片类药物的预期获益包括改善功能和生活质量， 降低过量和死亡的风险。意外的负面后果-如功能恶化， 自杀风险增加-已被确定为潜在危害，特别是对于高风险患者或当 阿片类药物以突然或无支持的方式减少。需要进行研究以更好地了解影响 随着阿片类药物处方和疼痛护理实践的时间推移，以患者为中心的结局发生了变化，包括疼痛， 相关功能、生活质量和死亡率。 创新：处方阿片类药物变化对退伍军人的影响（EPOCH）研究是一项前瞻性研究 接受LTOT治疗的VA患者的纵向队列研究和了解患者的独特资源 疼痛护理实践的变化。VA HSR&D资金支持建立一个全国性的 在2016年索引日期之前接受LTOT治疗至少6个月的271，892例VA患者的人群队列。一 采用两阶段分层抽样设计，确定一个具有代表性的样本， 参加一个混合模式（邮件和电话）调查。在14，160名患者中，9253名（65.3%）入组 调查小组。该项目将扩大分析范围，并将长期跟踪延长至总共五年。 具体目的：本研究的主要目的是了解阿片类药物变化的动态影响， 随着时间的推移，根据患者报告的结局和死亡率开处方。具体目标是：（1）检查 5年以上时变阿片类药物剂量与疼痛相关功能的相关性（主要结局）， 生活质量; 2）通过a）表征患者亚组来检查阿片类药物剂量减少的不同方法 随着时间的推移阿片类药物治疗的不同轨迹，然后B）评估阿片类药物治疗的相关性 轨迹与疼痛相关功能（主要结局）和生活质量; 3）检查 时变阿片类药物剂量与全因死亡率和生存率。 方法：本研究将继续对现有调查小组中的48名患者进行年度调查 基线后60个月，使用迄今为止证明有效的多接触方法。后续行动 问卷将包括疼痛相关功能和健康相关生活质量的重复测量， 患者报告的主要结局。来自VA管理的卫生服务、协变量和结局数据 数据库将与来自调查问卷的患者报告数据合并。分析将使用两组数据 接受LTOT治疗的VA患者-9253例患者的调查样本（目标1和目标2b）和全部 271，892例患者的人群队列（aim 2a和aim 3）。 实施/后续步骤：后续步骤取决于实际结果，但我们预计调查结果很重要 给退伍军人管理局领导、开处方的临床医生和慢性疼痛患者。我们会保持联系 在整个项目中与VA计划合作伙伴及时分享调查结果。我们将与 退伍军人参与小组致力于开发以患者为中心的传播方法。如果结果 我们将展示明确的最佳实践，我们将开发和测试干预措施，以在临床实践中实施这些措施。

Background: In response to evidence of serious harms and modest benefits associated with long-term opioid therapy (LTOT), 2016 guidelines from the Centers for Disease Control and Prevention (CDC) and 2017 guidelines from the Department of Veterans Affairs (VA) and Department of Defense (DoD) recommend limiting the frequency, intensity, and duration of opioid prescribing. For patients on LTOT, these guidelines recommend tapering to reduced doses or discontinuation if benefits do not clearly outweigh harms. VA initiatives to implement guideline recommendations have increased opioid reduction in practice and decreased prevalence of LTOT, but effects on patients are unclear. Research is needed to understand long-term effects of LTOT reduction or discontinuation on patients and how different treatment approaches may affect results. Significance/Impact: Intended benefits of opioid reduction include improved function and quality of life and decreased risk of overdose and death. Unintended negative consequences—such as worsened function and increased risk of suicide—have been identified as potential harms, especially for high-risk patients or when opioids are reduced in an abrupt or unsupported manner. Research is needed to better understand effects over time of opioid prescribing and pain care practice changes on patient-centered outcomes, including pain- related function, quality of life, and mortality. Innovation: The Effects of Prescription Opioid Changes for Veterans (EPOCH) study is a prospective longitudinal cohort study of VA patients treated with LTOT and a unique resource for understanding patient outcomes of pain care practice changes. VA HSR&D funding supported establishment of a nationwide population cohort of 271,892 VA patients treated with LTOT for at least 6 months before a 2016 index date. A two-stage stratified sampling design was used to identify a representative sample of patients who were invited to participate in a mixed-mode (mail and phone) survey. Of 14,160 patients invited, 9253 (65.3%) enrolled in the survey panel. This project will expand analyses and extend long-term follow-up to a total of five years. Specific Aims: The main objective of this study is to understand dynamic effects of changes in opioid prescribing on patient-reported outcomes and mortality over time. Specific aims are to: 1) examine associations over five years of time-varying opioid dose with pain-related function (primary outcome) and quality of life; 2) examine different approaches to opioid dose reduction by a) characterizing patient subgroups with distinct trajectories of opioid treatment over time and then b) evaluating associations of opioid treatment trajectories with pain-related function (primary outcome) and quality of life; and 3) examine associations of time-varying opioid dose with all-cause mortality and survival. Methodology: This study will continue annual survey waves with patients in the existing survey panel at 48 and 60 months after baseline, using a multiple-contact approach that has proven effective so far. Follow-up questionnaires will include repeated measures of pain-related function and health-related quality of life as the primary patient-reported outcomes. Health services, covariates, and outcome data from VA administrative databases will be merged with patient-reported data from questionnaires. Analyses will use data for two panels of VA patients treated with LTOT— the survey sample of 9253 patients (aim 1 and aim 2b) and the full population cohort of 271,892 patients (aim 2a and aim 3). Implementation/Next Steps: Next steps depend on the actual results, but we expect findings to be important to VA leaders, prescribing clinicians, and patients with chronic pain. We will maintain communication throughout the project with VA program partners to share findings in a timely manner. We will collaborate with a Veteran Engagement Panel on development of patient-centered dissemination approaches. If results demonstrate clear best practices, we will develop and test interventions to implement them in clinical practice.