儿科多发性硬化症和克雅氏病的系统性综述：评价罕见疾病治疗方法的缺陷
Systematic reviews in paediatric multiple sclerosis and Creutzfeldt-Jakob disease exemplify shortcomings in methods used to evaluate therapies in rare conditions
摘要：
背景：随机对照试验（RCT）是临床研究评估干预措施的金标准设计。然而，随机对照试验并不总是适用于实际或伦理的原因。为了调查罕见病的当前实践，我们回顾了儿科多发性硬化症（MS）和克雅氏病（CJD）治疗干预的评价。特别是，我们阐明了使用的终点，实施的研究设计和应用的统计方法。方法：我们进行了文献检索，以确定相关的主要研究。从选定的研究中提取研究设计、目的、终点、患者特征、随机化和设盲、干预类型、对照、退出和统计方法学数据。评估了偏倚风险和研究质量。结果：12（7）项关于儿科MS（CJD）的主要研究纳入定性综合。尚未发表评价儿科MS干预措施的双盲、随机、安慰剂对照试验。可获得来自一项开放标签RCT的证据。观察性研究是前后研究或对照研究。七项选定的关于克雅氏病的研究中有三项是随机对照试验，其中两项在牛津质量量表上获得最高分。4项试验为对照观察性研究。结论：来自双盲随机对照试验的关于治疗效果的证据似乎在罕见疾病之间存在差异。关于儿科疾病，监管机构将通过以下方式产生何种影响还有待观察：儿科研究计划。总的来说，通过使用创新的试验设计和数据分析技术，还有改进的空间。
英文摘要：
BACKGROUND: Randomized controlled trials (RCTs) are the gold standard design of clinical research to assess interventions. However, RCTs cannot always be applied for practical or ethical reasons. To investigate the current practices in rare diseases, we review evaluations of therapeutic interventions in paediatric multiple sclerosis (MS) and Creutzfeldt-Jakob disease (CJD). In particular, we shed light on the endpoints used, the study designs implemented and the statistical methodologies applied. METHODS: We conducted literature searches to identify relevant primary studies. Data on study design, objectives, endpoints, patient characteristics, randomization and masking, type of intervention, control, withdrawals and statistical methodology were extracted from the selected studies. The risk of bias and the quality of the studies were assessed. RESULTS: Twelve (seven) primary studies on paediatric MS (CJD) were included in the qualitative synthesis. No double-blind, randomized placebo-controlled trial for evaluating interventions in paediatric MS has been published yet. Evidence from one open-label RCT is available. The observational studies are before-after studies or controlled studies. Three of the seven selected studies on CJD are RCTs, of which two received the maximum mark on the Oxford Quality Scale. Four trials are controlled observational studies. CONCLUSIONS: Evidence from double-blind RCTs on the efficacy of treatments appears to be variable between rare diseases. With regard to paediatric conditions it remains to be seen what impact regulators will have through e.g., paediatric investigation plans. Overall, there is space for improvement by using innovative trial designs and data analysis techniques.
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