小儿手足口病随机对照试验设计要素的文献研究

Literature research on design elements in clinical randomized controlled trials of children with hand-foot-and-mouth disease

关键词:  手足口病  小儿  随机对照试验  试验设计

Key words:  hand,foot and mouth disease (HFMD)  children  randomized controlled trial  clinical tricals design

摘要:

[目的] 研究小儿手足口病(HFMD)临床随机对照试验的设计要素，为本病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。[方法] 通过文献研究，系统检索中国知网、万方数据库、维普数据库、Pubmed、Cochrane Library、Embas等数据库中近10年HMFD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，提炼该病临床试验设计与评价的主要技术要素。[结果] 检索出1 081篇文献，最终纳入14篇。小儿HFMD其临床试验目的均以缩短热程为主，2期/重症重型适应症也以减少危重症发生为主；试验总体设计均采用随机盲法，其中双盲设计5项(35.71%)；受试者选择均有明确的诊断标准或相应描述，以及纳入标准、排除标准设计；干预措施包括中药/中成药(4项，28.57%)、中药注射液(5项，35.71%)、抗病毒药(4项，28.57%)、免疫抑制剂(1项，7.14%)；14项研究均无导入期设计；总疗程3~10 d，普通型试验以3~7 d为主，重症重型研究以7~10 d为主；6项(42.86%)研究设计了3~15 d的随访期；主要有效性指标，多围绕发热(8项，57.14%)、危重症发生率(3项，21.43%)、皮疹(2项，14.29%)等进行评估。次要指标，可选择肠道病毒载体量/转阴率、住院时间、中医证候积分/疗效、病死率等。安全性指标以不良事件/不良反应为主要观察指标(13项，92.86%)。[结论] 纳入本研究的文献质量高，信息完善，研究结果涵盖了小儿手足口病临床试验设计与评价的主要技术要素，具有较高的借鉴价值。

Abstract:

[Objective] To study the design elements of clinical randomized controlled trial of hand,foot and mouth disease(HFMD) in children,and to provide reference and guidance for the standardized design of clinical trials,furthermore,to improve the feasibility of comparison of different test results.[Methods] Through literature research,we systematic retrieved Chinese and English literatures about HMFD clinical trials (RCTs) in the past 10 years in Chinese and English databases such as CNKI,Wanfang,VIP and PubMed,Cochrane Library databases,and extracted,analyzed and summarized literature that met the inclusion criteria,then abstracted the main technical elements for design and evaluation of clinical trials.[Results] The 1 081 articles were retrieved,14 articles were finally included. The clinical trials of pediatric HFMD were mainly aimed at shortening the heat course,and the second phase/severe indications were also mainly to reduce the occurrence of critical illness. All the tests were designed by random blind method,including 5 double-blind designs (35.71%). The selection of subjects had clear diagnostic criteria or corresponding descriptions,as well as inclusion criteria and exclusion criteria design. The intervention measures included Chinese medicine or Chinese patent medicine(4 items,28.57%),Chinese medicine injection (5 items,35.71%),antiviral drugs (4 items,28.57%),immunosuppressant (1 item,7.14%). The 14 studies had no lead-in period design. The total treatment course were 3~10 days,the general type test is mainly 3~7 days,the severe and severe test mainly were 7~10 days. The 6 (42.86%) studies designed a follow-up period of 3~15 days. The main effectiveness indicators,mostly around fever (8 items, 57.14%),the incidence of critical illness (3 items,21.43%) and skin rash (2 items,14.29%) were evaluated. Secondary indicators included the amount of enterovirus vector or negative conversion rate,hospitalization time,traditional Chinese medicine syndrome score or effect,mortality rate. The safety indicators were based on adverse events or adverse reactions as the main observation outcome (13 items,92.86%). [Conclusion] The quality of the literature included in this study was high,the information was complete. The research results covered the main technical elements of the design and evaluation of clinical trials for pediatric hand,foot and mouth disease,and have high reference value.