儿童变应性鼻炎药物临床试验设计与评价技术要素的文献研究

The literature research of clinical trial design and evaluation of allergic rhinitis drugs in children

关键词:  变应性鼻炎  儿童  中药  随机对照试验  试验设计

Key words:  allergic rhinitis  children  traditional Chinese medicine  randomized controlled trial  clinical trail design

摘要:

[目的] 研究儿童变应性鼻炎临床随机对照试验的设计要素，为病证结合类中药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，系统检索中国知网数据库（CNKI）、维普中文科技期刊数据库（VIP）、万方数据库（WF）、PubMed、Cochrane及Web of Science等中英文数据库中的儿童变应性鼻炎随机对照试验（RCT）文献，对符合纳入标准的文献进行资料提取、分析、归纳，提炼儿童变应性鼻炎临床试验设计与评价的主要技术要素。[结果] 检索出2 735篇文献，最终纳入18篇，包括中文5篇、英文13篇。全部研究，无论短期或远期治疗，临床定位均为缓解鼻部症状。试验总体设计均采用随机，全部研究以双盲为主12项（66.67%）；有样本量估算8项（44.44%）。受试者选择均有明确的西医诊断标准，以及纳入标准、排除标准设计。干预措施，全部研究分别为鼻内皮质类固醇和抗组胺药各5项（27.78%），中西医联合治疗和舌下免疫疗法各3项（16.67%），口服皮质类固醇和抗组胺药联合治疗、鼻用纤维素散各1项（5.56%）。对照药物的选择以安慰剂对照10项（55.57%）为主，也有阳性药对照6项（33.33%），其余为三臂试验设计2项（11.11%）。设计导入期8项（44.44%），时长为3 d～3周；疗程为1周～1年，以2～4周为主，其中，以中西医联合治疗、鼻部局部治疗及抗组胺药为干预措施者多为2～4周，以系统治疗为干预措施者可长达1年，甚至更久。主要有效性指标，采用变应性鼻炎症状体征综合疗效5项（27.78%）和症状/疾病严重程度评估12项（66.67%），其余1项（5.56%）采用无症状天数百分比；使用的评估工具包括鼻部症状总评分（TNSS）量表4项（22.22%），鼻部综合评分（RTSS）和总症状评分（TSS）量表各2项（11.11%），4项总症状评分（T4SS）、鼻部症状评分（NSS）、总症状严重程度评分（TSSC）、每日症状评分（DSS）量表各1项（5.56%），或3项鼻部症状总评分（3TNSS）、4项鼻部症状总评分（4TNSS）、眼部症状总评分（TOSS）量表联合应用1项（5.56%）。[结论] 纳入文献质量较高，信息完善，研究结果涵盖了病证结合模式下儿童变应性鼻炎药物临床试验设计与评价的主要技术要素，具有较高的借鉴和参考价值，为中华中医药学会标准化项目－《儿童变应性鼻炎中药临床试验设计与评价技术指南》的制定，提供了文献依据。

Abstract:

[Objective] To study the design elements of clinical randomized controlled trials in children with allergic rhinitis (AR),so as to provide reference and guidance for the standardized design of clinical trials of traditional Chinese medicine combined with disease and syndrome,,and improve the feasibility of comparing the results of different trials.[Methods] Through literature research,we searched Chinese and English databases of China National Knowledge Infrastructure (CNKI),China Science and Technology Journal Database (VIP),Wanfang Database (WF),PubMed,EMBASE and Web of Science for randomized controlled trials (RCT) of AR in children. We extracted,analyzed and summarized the literatures that met the inclusion criteria,and extracted the main technical elements for the design and evaluation of clinical trials of AR in children.[Results] A total of 2 735 articles were retrieved and 18 articles were included,including 5 in Chinese and 13 in English. In all studies,no matter short-term or long-term treatment,the clinical orientation was to relieve nasal symptoms.The overall design of the trial was randomized;There were 12 studies (66.67%) with double-blind and 8 studies (44.44%) with sample size estimation. There were clear diagnostic criteria of Western medicine,inclusion criteria and exclusion criteria. The intervention measures included intranasal corticosteroids and antihistamines (5 items,27.78%),combined traditional Chinese and Western medicine and sublingual immunotherapy (3 items,16.67%),oral corticosteroids and antihistamines (1 item,5.56%) and nasal cellulose powder (1 item,5.56%). There were 10 placebo-controlled drugs (55.57%),6 positive drug controlled drugs (33.33%) and 2 three arm trial designs (11.11%). The lead-in period of 8 items (44.44%) was 3 days to 3 weeks;The course of treatment ranged from 1 week to 1 year,mainly from 2 to 4 weeks. Among them,the patients with combined treatment of traditional Chinese medicine and Western medicine,nasal local treatment and antihistamines as intervention measures mostly lasted for 2 to 4 weeks,while the patients with systemic treatment as intervention measures could last as long as 1 year or even longer.The main efficacy indicators were as follows:5 items (27.78%) of comprehensive efficacy of AR symptoms and signs,12 items (66.67%) of symptom/disease severity assessment,and the rest 1 item (5.56%) of asymptomatic days percentage;The assessment tools used included TNSS 4 items (22.22%),RTSS and TSS 2 items (11.11%),T4SS,NSS,TSSC,DSS 1 item (5.56%),or 3TNSS,4TNSS,TOSS 1 item (5.56%).[Conclusion] The literatures included in this study are of high quality and complete information. The research results cover the main technical elements of clinical trial design and evaluation of AR drugs in childrenunder the mode of combination of disease and syndrome,,which has high reference valueand reference value. It provides a literature basis for the development of the standardization project of Chinese society of traditional Chinese Medicine "technical guide for clinical trial design and evaluation of Chinese medicine in children with allergic rhinitis".