Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) Trial

描述(由申请人提供)： 背景慢性肌肉骨骼疼痛是初级保健中最常见的问题之一。随着这些疾病对个人和社会健康的重要性越来越被认识到，长期阿片类药物治疗慢性肌肉骨骼疼痛的使用呈指数级增长。不幸的是，研究没有跟上处方实践的这种变化。尽管有证据支持阿片类镇痛剂有能力在短期内降低疼痛强度，但评估阿片类药物有效性的长期试验尚不存在。阿片类药物对功能和生活质量影响的证据有限，但观察数据表明，许多长期服用阿片类药物的患者继续经历严重的疼痛和功能限制。此外，文献中对阿片类药物的长期安全性描述很少。初步研究表明，阿片类药物治疗可能会对疼痛敏感性、内分泌功能、跌倒风险和睡眠产生不利影响，但这些潜在影响的发生率和严重程度尚未得到很好的量化。此外，尽管阿片类药物滥用和成瘾一直是大量关注的焦点，但对其流行率的估计是基于具有重要局限性的研究。目的比较两种处方策略：1)在治疗早期使用强阿片类药物，如吗啡；2)避免使用阿片类药物，在延迟和最小化阿片类药物使用的同时，优化非阿片类药物的使用。空间将在12个月内评估1)阿片类药物密集处方策略与阿片类药物回避药物处方策略对疼痛相关功能和疼痛强度的影响，2)阿片类药物密集处方策略与阿片类药物回避药物处方策略的不良影响。其次，我们将考察两种处方策略对健康相关生活质量、疼痛敏感性和异常药物相关行为的影响。我们还将进行二次定性分析，以更好地了解患者对干预反应的看法和干预成分的价值。方法SPACE是一项务实的随机临床试验，旨在比较两种临床相关的治疗慢性肌肉骨骼疼痛的处方策略在12个月内的有效性和安全性。符合条件的退伍军人将是那些在慢性背部或下肢关节炎疼痛的初级护理中看到的人，他们有中到重度的疼痛强度和功能干扰，尽管每天服用止痛药。目前正在接受慢性每日阿片类药物治疗的人将被排除在外。参与者将被随机分为阿片类药物密集组(n=138)或阿片类药物回避组(n=138)，按主要疼痛部位(背部或臀部/膝盖)分层。在考虑患者个人喜好和反应的同时，每个手臂上的药物将进行调整，以达到改善疼痛的目标。干预措施将在护理管理模型中提供，使用指定的处方策略、自动症状监测和结构化决策方法来指导用药调整。戴着治疗分配面具的结果评估员将进行访谈，以评估患者在0、3、6、9和12个月时报告的结果，并将在0、6和12个月评估疼痛敏感度、身体表现和认知功能。对于主要结果，简明疼痛问卷(BPI)干涉量表，该研究将有80%的能力来检测两组之间1分的差异，假设双侧α=0.05和20%的磨损。分析将使用意向治疗方法，包括他们最初被分配到的手臂上的所有参与者。

DESCRIPTION (provided by applicant): Background Chronic musculoskeletal pain conditions are among the most common problems seen in primary care. As the importance of these conditions for the health of individuals and society has been increasingly recognized, use of long-term opioid therapy for chronic musculoskeletal pain has grown exponentially. Unfortunately, research has not kept pace with this change in prescribing practice. Although evidence supports the ability of opioid analgesics to produce short-term reductions in pain intensity, long-term trials evaluating opioid effectiveness are not available. Evidence for effects of opioids on function and quality of life ar limited, but observational data indicate that many patients treated with long-term opioids continue to experience severe pain and functional limitations. Furthermore, the long-term safety of opioids is poorly described in the literature. Preliminary investigations suggest that opioid therapy may adversely affect pain sensitivity, endocrine function, fall risk, and sleep, but the incidence and severity of these potential effects have not been well-quantified. Additionally, although opioid misuse and addiction have been the focus of substantial attention, estimates of their prevalence are based on research with important limitations. Objectives The main objective of the Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) Trial are to compare two prescribing strategies: 1) an opioid-intensive strategy that uses strong opioids, such as morphine, early in treatment, and 2) an opioid-avoidant strategy that optimizes non-opioid medications while delaying and minimizing opioid use. SPACE will evaluate, over 12 months, 1) the effects of opioid-intensive versus opioid-avoidant prescribing strategies on pain-related function and pain intensity and 2) the adverse effects of opioid-intensive versus opioid-avoidant prescribing strategies. Secondarily, we will examine effects of the two prescribing strategies on health-related quality of life, pain sensitivity, and aberrant drug-related behaviors We will also conduct a secondary qualitative analysis to better understand patients' perceptions of their response to the intervention and of the value of intervention components. Methods SPACE is a pragmatic randomized clinical trial designed to compare the effectiveness and safety over 12 months of two clinically-relevant prescribing strategies for chronic musculoskeletal pain. Eligible Veterans will be those seen in primary care for chronic back or lower-extremity arthritis pain who have moderate-severe pain intensity and interference with function despite daily analgesics. Those currently receiving chronic daily opioid therapy will be excluded. Participants will be randomized to the opioid-intensive (n=138) or the opioid-avoidant (n=138) arm, with stratification by primary pain location (back or hip/knee). Medications in each arm will be adjusted to target improvement in pain, while considering individual patient preferences and responses. Interventions will be delivered in a care management model using the assigned prescribing strategies, automated symptom monitoring, and a structured decision-making approach to guide medication adjustment. Outcome assessors masked to treatment assignment will conduct interviews to assess patient-reported outcomes at 0, 3, 6, 9, and 12 months and will assess pain sensitivity, physical performance, and cognitive function at 0, 6, and 12 months. For the primary outcome, the Brief Pain Inventory (BPI) Interference scale, the study will have 80% power to detect a 1 point difference between groups, assuming 2-sided alpha=0.05 and 20% attrition. Analysis will use an intent-to-treat approach, including all participants in the arm to which they were originally assigned.