Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) Trial

描述（由申请人提供）： 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。虽然有证据支持阿片类镇痛剂能够在短期内减轻疼痛强度，但尚无评价阿片类镇痛剂有效性的长期试验。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，许多长期接受阿片类药物治疗的患者继续经历重度疼痛和功能限制。此外，文献中对阿片类药物的长期安全性描述不足。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，虽然类阿片滥用和成瘾一直是人们高度关注的焦点，但对其流行率的估计所依据的研究存在重大局限性。镇痛药处方策略比较有效性（SPACE）试验的主要目的是比较两种处方策略：1）阿片类药物密集策略，在治疗早期使用强效阿片类药物，如吗啡，2）阿片类药物回避策略，优化非阿片类药物，同时延迟和尽量减少阿片类药物的使用。SPACE将在12个月内评估1）阿片类药物强化与阿片类药物回避处方策略对疼痛相关功能和疼痛强度的影响，以及2）阿片类药物强化与阿片类药物回避处方策略的不良影响。其次，我们将检查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措施的反应和干预措施的价值。方法SPACE是一项实用的随机临床试验，旨在比较两种临床相关处方策略治疗慢性肌肉骨骼疼痛的有效性和安全性。合格的退伍军人将是那些在初级保健慢性背部或下肢关节炎疼痛谁有中度至重度疼痛强度和干扰功能，尽管每天止痛。目前接受长期每日阿片类药物治疗的患者将被排除在外。参与者将随机分配至阿片类药物强化组（n=138）或阿片类药物回避组（n=138），并按原发性疼痛部位（背部或髋关节/膝关节）进行分层。将调整每组中的药物以改善疼痛，同时考虑个体患者的偏好和反应。干预措施将在护理管理模型中使用指定的处方策略、自动化症状监测和结构化决策方法来指导药物调整。对治疗分配设盲的结局评估者将在0、3、6、9和12个月时进行访谈，以评估患者报告的结局，并将在0、6和12个月时评估疼痛敏感性、身体表现和认知功能。对于主要结局，即简明疼痛量表（BPI）干扰量表，假设双侧α =0.05和20%损耗，研究将有80%的把握度检测到组间1分的差异。分析将使用意向治疗方法，包括最初分配的组中的所有受试者。

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.