小儿急性支气管炎临床随机对照试验设计要素的文献研究

Literature study on design elements of randomized controlled trials for acute bronchitis in children

目的研究小儿急性支气管炎临床随机对照试验的设计要素,为病证结合类临床试验的标准化设计提供借鉴和指导,提高不同试验结果比较的可行性。同时,也为中华中医药学会标准化项目——《儿科系列常见病中药临床试验设计与评价技术指南-急性支气管炎》的制定提供文献依据。方法通过文献研究,系统检索中文学术期刊全文数据库(CNKI)、维普中文科技期刊数据库(VIP)、中国生物医学文献数据库(CMB)、万方数据库(Wanfang Data)、中国临床试验注册中心、PubMed、Embase、Cochrane Library、Clinical Trials数据库中1999—2020年关于小儿急性支气管炎随机对照临床试验(RCT)中英文文献,对符合纳入标准的文献进行资料提取、分析、归纳,提炼小儿急性支气管炎临床试验设计与评价的主要技术要素。结果检索出1542篇文献,最终纳入19篇RCTs,包括中文17篇、英文2篇。目标定位,17项(89.47%)研究的主要目的为改善病情/症状,1项(5.26%)为缩短病程,1项(5.26%)以改善中医证候为主要目的;试验总体设计均采用随机方法,以双盲为主的研究14项(73.68%),仅提及使用盲法1项(5.26%),其余4项未提及盲法设计(21.05%);采用阳性药对照14项(73.68%),安慰剂对照5项(26.32%);多中心研究17项(89.47%);估算样本量4项(21.05%);差异性检验设计15项(78.95%),非劣效检验设计3项(15.79%),优效性检验1项(5.26%);全部研究中,具有明确的西医诊断标准者16项(84.21%),有明确中医诊断与辨证标准者16项(84.21%);受试者的选择与退出,全部研究均有纳入标准设计,而有排除标准描述者16项(84.21%);干预措施,纳入的19项研究中,干预措施为中成药的16项(84.21%)、中西药联合应用1项(5.26%)和植物药2项(10.53%),有基础治疗设计的1项(5.26%);试验流程,19项研究均未设置导入期,设计随访研究1项(5.26%),随访时间为3~7 d;疗程5~7 d,以5 d为主;有效性评价,19项研究,以疾病有效率/愈显率、BSS或BSS-ped为主要评价指标的有13项(68.42%),以咳嗽、咳痰、气促/喘息或肺部体征评分为主要评价指标的有3项(15.79%),以咳嗽症状积分与时间(天)的曲线下面积(AUC)为主要评价指标的有1项(5.26%),以中医证候有效率为主要评价指标1项(5.26%),以主要症状(咳嗽、咳痰)基本消失时间为主要评价指标1项(5.26%);安全性评价,19项研究均有安全性指标设计;有2项(10.53%)研究提到试验质量控制;全部研究中,有伦理批件号说明的仅2项(10.53%)。结论纳入本研究的文献质量高,信息完善,严格遵守循证医学原则,贴近临床实际,突出中药特色,研究结果涵盖了小儿急性支气管炎临床试验设计与评价的主要技术要素,对中成药治疗小儿急性支气管炎试验设计关键环节和常见问题进行了分析总结,具有较高的借鉴价值,为不同文献之间的结果比较和系统评价,提供了可行性。

Objective To study the design elements of randomized controlled trials for acute bronchitis in children,to provide reference and guidance for the standardized design of clinical trials combining disease and syndrome,and to improve the feasibility of comparing the results of different trials.At the same time,it provides a literature basis for the development of the standardization project of Chinese society of traditional Chinese medicine(TCM)——"technical guide for clinical trial design and evaluation of Chinese medicine in children with acute bronchitis".Methods Through literature research,CNKI,VIP,CMB,Wanfang Data,China Clinical Trial Registry,PubMed,Embase,Cochrane Library and Clinical Trials database were systematically searched Chinese and English literature on randomized controlled clinical trials(RCTs)of pediatric acute bronchitis from 1999 to 2020 were collected.Data were extracted,analyzed and summarized from the literature that met the inclusion criteria,and the main technical factors for clinical trial design and evaluation of pediatric acute bronchitis were extracted.Results 1542 articles were retrieved,and finally 19 articles were included,including 17 in Chinese and two in English.According to the target orientation,the main purpose of 17(89.47%)studies was to improve the disease/symptoms,one(5.26%)to shorten the course of disease,and one(5.26%)to improve TCM syndromes.The overall design of the trial was randomized.All studies were double-blind in 14(73.68%),1(5.26%)only mentioned the use of blind method,and the other four did not mention blind design(21.05%).There were 14 positive drug controls(73.68%),five placebo controls(26.32%),17 multicenter studies(89.47%),four estimated sample sizes(21.05%),15 difference test designs(78.95%),three non-inferiority test designs(15.79%)and one superiority test(5.26%).Among all the studies,16(84.21%)had clear diagnostic criteria of western medicine and 16(84.21%)had clear criteria of diagnosis and syndrome differentiation of traditional Chinese medicine,while 16(84.21%)excluded standard descriptions.Among the 19 included studies,intervention measures included 16 cases of Chinese patent medicine therapy(84.21%),1 case of combined application of Chinese and Western medicine(5.26%),two cases of plant medicine(10.53%),and one case of basic treatment design(5.26%).There was no initiation period for all 19 studies.One follow-up study(5.26%)was designed,and the follow-up time was three to seven days.The course of treatment is five to seven days,mainly for five days.Effectiveness evaluation,among 19 studies,13(68.42%)took disease response rate/recovery rate,BSS or BPS-PED as the main evaluation indexes,and three(15.79%)took cough,expectoration,shortness of breath/wheezing or pulmonary signs score as the main evaluation indexes.There was one(5.26%)cough symptom integral and time(days)area under the curve(AUC)as the main evaluation index,one(5.26%)TCM syndrome effective rate as the main evaluation index,and one(5.26%)time of the main symptoms(cough and expectoration)basically disappeared as the main evaluation index.Safety evaluation,19 studies have safety index design;two studies(10.53%)mentioned test quality control;in all studies,there are only two ethical batch numbers(10.53%).Conclusion The literature included in this study is of high quality and complete information.The research results cover the main technical elements for the design and evaluation of clinical trials of acute bronchitis in children,the key links and common problems in the trial design of Chinese patent medicine for the treatment of pediatric acute bronchitis were analyzed and summarized,which has a high reference value and provides feasibility for the results comparison and systematic evaluation among different literatures.