Pain Research and Nuffield Division of Anaesthetics, Nuffield Department of Clinical Neurosciences, University of Oxford, The Churchill, Oxford OX3 7LE, UK.
Br J Anaesth. 2013 Jul;111(1):38-45. doi: 10.1093/bja/aet126.
The process of systematic review has shone a light on the methodology of randomized controlled trials. Notably, a range of potential biases hinders the interpretation of chronic pain trials. These include a consistent bias favouring active over placebo in trials that are small and of short duration. The use of the 'last observation carried forward' imputation method is known to inflate results, often generating statistically significance when adverse event withdrawals are high; in clinical practice terms, this is the wrong answer. Patients want outcomes of low pain scores, large reductions in pain and relief from associated symptoms, with improvements in ability to function and in quality of life. Some patients achieve this, but many do not. The distribution of benefit is skewed and the use of average pain scores, or change in pain, can be misleading compared with responder analysis in which withdrawal is regarded as non-response. Historically, chronic pain trials have had a simple classic or a crossover design. They have been small and short, and used inappropriate imputation and outcomes unconnected to the experiences of most patients. While these designs are useful for answering some questions, they may be insensitive for many interventions. Newer designs, like enriched enrolment randomized withdrawal (EERW) trials or clinical effectiveness trials, are potentially more interesting and informative.
系统评价的过程揭示了随机对照试验的方法学。值得注意的是，一系列潜在的偏倚阻碍了慢性疼痛试验的解释。这些偏倚包括在规模小、持续时间短的试验中，活性药物相对于安慰剂的一贯优势偏向。人们知道，“最后一次观测结转”推断方法的使用会夸大结果，当不良事件退出率较高时，往往会产生统计学意义；从临床实践的角度来看，这是错误的答案。患者希望疼痛评分低、疼痛大幅减轻、相关症状缓解、功能改善和生活质量提高。一些患者实现了这一目标，但许多患者没有。受益分布存在偏倚，与将退出视为无反应的应答者分析相比，平均疼痛评分或疼痛变化可能具有误导性。从历史上看，慢性疼痛试验具有简单的经典或交叉设计。它们规模小、持续时间短，并且使用了不适当的推断方法和与大多数患者的经历无关的结果。虽然这些设计对于回答某些问题很有用，但对于许多干预措施可能不够敏感。较新的设计，如富集入组随机停药（EERW）试验或临床效果试验，可能更有趣和信息丰富。
