儿童轮状病毒感染治疗药物随机对照试验设计的系统评价

Systematic review on the design of randomized controlled trials about therapeutic drugs for rotavirus infection in children

目的系统分析儿童轮状病毒感染治疗药物的相关临床研究,为提升临床试验实施过程的科学性和规范性提供参考。方法系统检索PubMed、the Cochrane Library和Embase数据库,纳入2000-2022年发表的儿童轮状病毒感染治疗药物随机对照试验(RCT)的英文文献。筛选文献、提取资料后,采用Cochrane系统评价员手册推荐的偏倚评价量表对纳入文献进行质量评价,对其研究目的、试验设计、受试者的选择与退出、干预措施、疗程、随访、有效性与安全性评价、试验结果等进行描述性分析。结果与结论共纳入17项RCT,共计1345例儿童受试者。研究目的包括缓解轮状病毒感染引起的腹泻发作,促进粪便中轮状病毒脱落,改善脱水、发热、呕吐等临床症状,缩短住院时间等;所有研究均采用随机方法,均为单中心研究,多采用双盲设计(13项)和安慰剂对照(16项),且64.71%的研究有样本量估算;受试者的纳入与排除标准涉及腹泻发作情况、病毒检测情况、临床症状、病种、试验用药物等;干预措施包括益生菌(8项)、生物制剂(3项)、抗感染药(3项)等,疗程以1~5 d为主(13项);58.82%的研究设计了随访;有效性评价主要针对腹泻发作情况,微生物学试验和粪便培养结果,脱水、发热及呕吐等临床症状,住院时间或症状持续时间等,指标评价标准包括Vesikari量表、WHO推荐标准及研究者相关记录等;有10项研究对不良事件/不良反应进行了观察;仅有1项研究列出了伦理批件号。纳入研究的文献信息涵盖了儿童轮状病毒感染治疗药物RCT设计的基本要素,但均为单中心研究,部分研究缺乏样本量估算依据及基础治疗之外的合并用药情况,质量有待提升。今后应进一步开展高质量的多中心临床试验,以客观测量指标为主要有效性结果,并重视伦理审查和药物安全性评价。

OBJECTIVE To systematically analyze the related clinical research of therapeutic drugs for rotavirus infection in children,and to provide reference for the improvement of scientific and normative implementation in clinical trials.METHODS PubMed,the Cochrane Library and Embase databases were systematically searched,and English literature on randomized controlled trials(RCTs)about therapeutic drugs for pediatric rotavirus infection published between 2000 and 2022 was included.After literature screening and data extraction,the quality of the included literature was evaluated using the bias risk assessment scale recommended by Cochrane Handbook for Systematic Reviews.The research objectives,overall design,subject inclusion and exclusion criteria,interventions,course of treatment,follow-up visits,efficacy and safety evaluations,and results were analyzed descriptively.RESULTS&CONCLUSIONS A total of 17 RCTs were included,involving 1345 subjects.The purpose included relieving rotavirus infection-induced diarrhea,promoting rotaviral shedding,improving clinical symptoms such as dehydration,fever,vomiting,and shortening hospital stays,etc.All trials were randomized and single-center studies,mostly double-blind(13 trials)and placebo-controlled(16 trials),and 64.71%had sample size estimation.The inclusion and exclusion criteria included diarrhea attack,virus detection,clinical symptoms,disease types and drugs,etc.The interventions included probiotics(8 trials),biological agents(3 trials),anti-infective agents(3 trials),etc.Most of treatment course was 1-5 days(13 trials).A total of 58.82%were designed for follow-up.In the validity evaluation,diarrhea attack,microbiology test and fecal culture,clinical symptoms such as dehydration,fever and vomiting,length of hospital stays or duration of symptoms were included.Vesikari scale,WHO criteria and researcher evaluation were the evaluation criteria.In the safety evaluation,10 trials were designed for adverse events/adverse reaction observation;only one trial listed ethical approval numbers.The information of literature included in the study covers the basic elements for the design of RCTs of drugs for rotavirus infection in children.Nevertheless,all are single�center studies.Partial studies lack the basis for sample size estimation and related contents of drug combination,and the quality needs to be improved.In the future,the high-quality multi-center clinical trials should be further conducted,with objective measurement indexes as the validity results,and the ethical review and safety evaluation should be emphasized.