Huber Adam M, Tomlinson George A, Koren Gideon, Feldman Brian M
Division of Pediatric Rheumatology, IWK Health Centre and Dalhousie University, Halifax, Nova Scotia, Canada.
J Rheumatol. 2007 May;34(5):1125-32. Epub 2007 Apr 15.
Using serial N-of-1 trials and subsequent analysis with Bayesian methods may allow study of therapies using small numbers of subjects. Our research questions were: (1) Can serial N-of-1 trials analyzed with Bayesian statistical techniques be used to estimate the population effect of a therapeutic intervention? (2) Compared to placebo, how likely is it that low-dose amitriptyline therapy in children aged 10-18 years with active polyarticular-course juvenile idiopathic arthritis (JIA) results in a significant improvement in pain?
Six children (age 10.3-16.3 yrs, 4 girls) were enrolled. There were 3 pairs of randomized, double-blinded treatments (amitriptyline 25 mg or placebo) per participant. Each treatment lasted 2 weeks, with a 1 week washout. The primary outcome was pain, measured by 10 cm visual analog scale. Assessments were at the beginning and end of each treatment. A Bayesian statistical model was used to determine the treatment effect. Values < 0 indicated superiority of amitriptyline.
Bayesian techniques were used successfully to obtain estimates of population effect, despite the small number of participants. The mean treatment effect for pain was 0.67 (SD 0.89, 95% credible interval -0.99, 2.55). The probability that the treatment effect was < 0 was only 16%.
These methods can be used successfully to estimate population effects when sample sizes are small. It is unlikely that amitriptyline reduced pain by a clinically significant amount in these children with polyarticular JIA. These methods may be particularly suited to pilot studies and the study of rare illnesses.
采用系列单病例试验并随后运用贝叶斯方法进行分析，或许能够在受试者数量较少的情况下对治疗方法展开研究。我们的研究问题如下：（1）运用贝叶斯统计技术分析的系列单病例试验能否用于估计治疗性干预的总体效应？（2）相较于安慰剂，10 - 18岁患有活动性多关节型幼年特发性关节炎（JIA）的儿童使用低剂量阿米替林治疗后疼痛得到显著改善的可能性有多大？
招募了6名儿童（年龄10.3 - 16.3岁，4名女孩）。每位参与者有3组随机、双盲治疗（25毫克阿米替林或安慰剂）。每次治疗持续2周，有1周的洗脱期。主要结局为疼痛，通过10厘米视觉模拟量表进行测量。在每次治疗开始和结束时进行评估。使用贝叶斯统计模型来确定治疗效果。值<0表明阿米替林具有优越性。
尽管参与者数量较少，但贝叶斯技术成功用于获得总体效应的估计值。疼痛的平均治疗效果为0.67（标准差0.89，95%可信区间 - 0.99，2.55）。治疗效果<0的概率仅为16%。
当样本量较小时，这些方法可成功用于估计总体效应。在这些多关节型JIA儿童中，阿米替林不太可能在临床上显著减轻疼痛。这些方法可能特别适用于试点研究和罕见疾病的研究。
