School of Public Health, Sydney Medical School, The University of Sydney, Australia.
Department of General Practice, Erasmus MC, Rotterdam, The Netherlands.
Br J Clin Pharmacol. 2017 Nov;83(11):2347-2355. doi: 10.1111/bcp.13350. Epub 2017 Aug 11.
To investigate the use of an enriched study design on the estimates of treatment effect in analgesic trials for chronic musculoskeletal pain.
Database searches were conducted from 2004 to 2014. We included randomized placebo-controlled trials evaluating pain medications for chronic musculoskeletal pain. Methodological quality was assessed using the PEDro scale. The estimates of treatment effect on pain and adverse events were compared between enriched and nonenriched designs. Metaregression was used to assess the association between the effect size estimate and the study design controlling for analgesic dose and methodological quality.
We included 108 trials, of which 99 were included in the meta-analysis (n = 44 171). There were no overall differences in effect sizes between enriched and nonenriched designs for pain intensity. There was a significant difference for a reduction in any adverse events favouring enriched designs for opioids, but not for other analgesics or the outcome serious adverse events. There was an association between effect size and methodological quality, with failure to blind the outcome assessor and failure to use intention-to-treat analysis being associated with larger effect sizes.
There is no evidence that the use of an enriched study design changes the treatment effect size estimate for pain. There is some evidence that clinical trials that employ enriched designs report a reduced risk of adverse events in trials for chronic musculoskeletal pain, but it is unclear whether enriched designs influence estimates of serious adverse events. Features of trial design and study quality were associated with treatment effect estimates.
研究在慢性肌肉骨骼疼痛的镇痛试验中，使用强化研究设计对治疗效果估计的影响。
从 2004 年到 2014 年进行了数据库搜索。我们纳入了评估慢性肌肉骨骼疼痛疼痛药物的随机安慰剂对照试验。使用 PEDro 量表评估方法学质量。比较强化设计和非强化设计之间疼痛和不良反应治疗效果的估计值。使用元回归来评估在控制镇痛剂量和方法学质量的情况下，治疗效果估计值与研究设计之间的关联。
我们纳入了 108 项试验，其中 99 项试验纳入了荟萃分析（n=44171）。在疼痛强度方面，强化设计和非强化设计之间的效果大小没有总体差异。对于减少任何不良反应，阿片类药物的强化设计效果显著，但其他镇痛药或严重不良反应的结果则不然。治疗效果与方法学质量之间存在关联，结局评估者未设盲和未使用意向治疗分析与较大的效果大小有关。
没有证据表明使用强化研究设计会改变疼痛的治疗效果估计值。有一些证据表明，采用强化设计的临床试验报告慢性肌肉骨骼疼痛试验中不良反应风险降低，但尚不清楚强化设计是否会影响严重不良反应的估计值。试验设计和研究质量的特征与治疗效果估计值有关。
