Departments of Anesthesiology and Neurology and Center for Human Experimental Therapeutics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
Pain Med. 2011 Jul;12 Suppl 3:S109-17. doi: 10.1111/j.1526-4637.2011.01159.x.
There has been considerable progress identifying pathophysiologic mechanisms of neuropathic pain, but analgesic medications with improved efficacy, safety, and tolerability still represent an unmet public health need. Numerous treatments examined in recent randomized clinical trials (RCTs) have failed to show efficacy for neuropathic pain, including treatments that had previously demonstrated efficacy. This suggests that at least some negative results reflect limited assay sensitivity of RCTs to distinguish efficacious treatments from placebo. Patient characteristics, clinical trial research designs and methods, outcome measures, approaches to data analysis, and statistical power may all play a role in accounting for difficulties in demonstrating the benefits of efficacious analgesic treatments vs placebo. The identification of specific clinical trial characteristics associated with assay sensitivity in existing data has the potential to provide an evidence-based approach to the design of analgesic clinical trials. The US Food and Drug Administration recently launched the Analgesic Clinical Trial Innovations, Opportunities, and Networks (ACTION) public-private partnership, which is designed to facilitate the discovery and development of analgesics with improved efficacy, safety, and tolerability for acute and chronic pain conditions. ACTION will establish a collaborative effort to prioritize research objectives, develop a standardized analgesic database platform, and conduct methodologically focused studies to increase the assay sensitivity and efficiency of analgesic clinical trials. The results of these activities have the potential to inform and accelerate the development of improved pain management interventions of all types, not just pharmacologic treatments.
在确定神经病理性疼痛的病理生理机制方面已经取得了相当大的进展，但仍需要具有更好疗效、安全性和耐受性的镇痛药物。在最近的随机临床试验 (RCT) 中，许多经过检查的治疗方法都未能显示出对神经病理性疼痛的疗效，包括以前显示有效的治疗方法。这表明，至少一些负面结果反映了 RCT 在区分有效治疗方法与安慰剂方面的检测灵敏度有限。患者特征、临床试验研究设计和方法、结局指标、数据分析方法和统计能力都可能在解释证明有效镇痛治疗与安慰剂相比的益处方面发挥作用。在现有数据中确定与检测灵敏度相关的特定临床试验特征，有可能为设计镇痛临床试验提供一种基于证据的方法。美国食品和药物管理局最近启动了“镇痛临床试验创新、机会和网络”（ACTION）公私合作伙伴关系，旨在促进具有更好疗效、安全性和耐受性的急性和慢性疼痛治疗药物的发现和开发。ACTION 将建立一个合作努力，确定研究目标的优先级，开发标准化的镇痛数据库平台，并进行方法学重点研究，以提高镇痛临床试验的检测灵敏度和效率。这些活动的结果有可能为所有类型的改进疼痛管理干预措施的开发提供信息和加速，而不仅仅是药物治疗。
