Miller Christopher J, Bilker Warren B, DeLorey Ian, Argoff Charles E, Bell Russell L, Conroy Andrew, Gewandter Jennifer S, Gilron Ian, Haythornthwaite Jennifer A, Katz Nathaniel P, McWilliams Tara, Theken Katherine N, Farrar John T
Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Department of Neurology, Albany Medical Center, Albany, NY, United States.
Pain. 2025 May 9. doi: 10.1097/j.pain.0000000000003645.
The lack of established minimum clinically important differences in acute pain has made it challenging to interpret efficacy in analgesic trials. We performed a patient-level re-analysis of double-blind, placebo-controlled trials submitted to the US Food and Drug Administration to estimate minimum clinically important differences in acute postoperative pain. Trials were categorized by acute surgical pain model: dental extraction, bunionectomy, orthopedic surgery, and soft tissue surgery. Pain intensity was assessed using the 0 to 10 numeric rating scale (NRS) or 0 to 100 visual analog scale, with visual analog scale scores converted to NRS for analysis. To avoid misclassification from arbitrary thresholds on global impression of change or pain relief scales, meaningful pain relief was determined using the double-stopwatch technique, where patients actively indicated the times they experienced perceptible and meaningful relief. Across 29 trials, 9047 patients with moderate-to-severe baseline pain were included. Patients with severe baseline pain (NRS ≥7) reported meaningful relief at a higher absolute NRS and required larger absolute reductions in pain intensity than those with moderate baseline pain (NRS 4-<7). However, the percent reduction in pain at meaningful relief remained stable across baseline pain levels, suggesting patients assess meaningful relief in relative rather than absolute terms. No appreciable differences in the changes in pain at meaningful relief were observed by age, sex, drug, or route of administration. Receiver operating characteristic curve analysis identified a 50% reduction in pain intensity as a consistent and clinically meaningful threshold across surgical pain models, supporting its use as a standardized patient-centric metric for evaluating analgesic efficacy.
急性疼痛缺乏既定的最小临床重要差异，这使得在镇痛试验中解释疗效具有挑战性。我们对提交给美国食品药品监督管理局的双盲、安慰剂对照试验进行了患者层面的重新分析，以估计急性术后疼痛的最小临床重要差异。试验按急性手术疼痛模型分类：拔牙、拇囊炎切除术、骨科手术和软组织手术。使用0至10数字评分量表（NRS）或0至100视觉模拟量表评估疼痛强度，将视觉模拟量表分数转换为NRS进行分析。为避免因对整体变化印象或疼痛缓解量表的任意阈值导致的错误分类，使用双秒表技术确定有意义的疼痛缓解，即患者主动指出他们经历可感知和有意义缓解的时间。在29项试验中，纳入了9047例基线疼痛为中度至重度的患者。基线疼痛严重（NRS≥7）的患者报告有意义缓解时的绝对NRS更高，且与基线疼痛中度（NRS 4-<7）的患者相比，疼痛强度需要更大的绝对降低。然而，有意义缓解时疼痛的降低百分比在不同基线疼痛水平上保持稳定，这表明患者以相对而非绝对的方式评估有意义的缓解。在有意义缓解时，未观察到年龄、性别、药物或给药途径对疼痛变化有明显差异。受试者工作特征曲线分析确定疼痛强度降低50%是所有手术疼痛模型中一致且具有临床意义的阈值，支持将其用作评估镇痛疗效的以患者为中心的标准化指标。
