摘要
目的分析目前儿童罕见病药物干预研究的现况,为罕见病药物干预研究的研究设计提供依据。方法对30项研究开始时间为2008年1月至2018年12月的儿童神经系统罕见病的国外临床研究的各环节进行数据收集及分析,并对研究发起者与研究中心、入组数量与患病率关系等进行统计学分析。结果纳入的30项研究涉及6种疾病类别,14种疾病。(1)全球多中心研究(14项)均由医药公司发起,多数单中心(6/7种,86%)和单一国家的多中心研究(7/9种,78%)由研究者发起,研究中心与研究发起者之间明显相关(P<0.001);(2)研究药物的选择依据:以既往临床试验(9/30项)及动物实验(9/30项)最为常见;(3)样本量:入组患儿的中位数为39(10~215)例,60%(18/30项)入组数量小于50例;(4)研究设计方法:53%(16/30项)为随机平行对照研究,33%(10/30项)为单组开放性研究,14%(4/30项)为随机交叉对照研究,75%(12/16项)随机平行对照研究由医药公司发起,50%(5/10项)单组开放性研究及所有(4/4项)随机交叉对照研究由研究者发起,研究设计方法与研究发起者之间明显相关(χ^2=7.602,P=0.022);(5)疗效评价指标:50%(15/30项)将量表评分的改善作为主要结局指标,尚有研究将临床症状的改善、病理检查改变等作为主要结局指标。结论儿童罕见病药物干预研究入组数量明显少于其他常见病的研究,且研究设计方法较为单一,需要进行全球、多中心招募及药企的参与,并优化研究设计方法以提高临床研究的证据级别。
Objective To explore the methods for generating evidence on health outcomes in children with rare diseases.Methods The data from 30 clinical trials on rare neurological diseases in children from January 2008 to December 2018 were collected and analyzed.Statistical analysis was conducted on the relationship between the study sponsor and the study center,the number of participants and the prevalence rate.Results Thirty studies involved 6 types of diseases,including 14 kinds of diseases.(1)All global multicenter studies(14 items)were initiated by pharmaceutical companies,whereas most of single-center studies(6/7 kinds,86%)and multiple centers within one country(7/9 kinds,78%)were initiated by investigators.There was a significant correlation between the research center and the research sponsor(P<0.001).(2)Most of the drugs studied were selected based on previous clinical trials(9/30 items)and animal experiments(9/30 items).(3)The median number of participants included 39 cases(10-215 cases),and 60%(18/30 items)of the studies was fewer than 50 cases.(4)Study design:53%(16/30 items)of studies were randomized controlled studies,33%(10/30 items)studies were open-label single-arm studies,and 14%(4/30 items)were randomized cross-over trials.Seventy-five percent(12/16 items)of randomized controlled studies were initiated by pharmaceutical companies,50%(5/10 items)open-label single-arm studies and all randomized cross-over trials were initiated by investigators.There was a statistical correlation between the study sponsors and the study design method(χ2=7.602,P=0.022).(5)Outcome index:Scale score was used as the primary outcome in half of studies.Other studies used symptom improvement or pathological changes.Conclusions Clinical trials in rare diseases enrolled fewer participants than that in non-rare diseases,and the study design method was relatively simple.Therefore,it is necessary to further improve the level of evidence of clinical research of rare diseases through global and multi-center recruitment,initiation of pharmaceutical companies and improving the study design method.
作者
常旭婷
张捷
吴晔
Chang Xuting;Zhang Jie;Wu Ye(Department of Pediatrics,Peking University First Hospital,Beijing 100034,China)
出处
《中华实用儿科临床杂志》
CSCD
北大核心
2019年第24期1891-1894,共4页
Chinese Journal of Applied Clinical Pediatrics
关键词
儿童
罕见病
药物干预研究
研究设计方法
Child
Rare diseases
Drug intervention study
Research design method
