目的 研究小兒急性支氣管炎臨床隨機對照試驗的設(shè)計要素，為病證結(jié)合類臨床試驗的標(biāo)準(zhǔn)化設(shè)計提供借鑒和指導(dǎo)，提高不同試驗結(jié)果比較的可行性。同時，也為中華中醫(yī)藥學(xué)會標(biāo)準(zhǔn)化項目——《兒科系列常見病中藥臨床試驗設(shè)計與評價技術(shù)指南-急性支氣管炎》的制定提供文獻依據(jù)。方法 通過文獻研究，系統(tǒng)檢索中文學(xué)術(shù)期刊全文數(shù)據(jù)庫（CNKI）、維普中文科技期刊數(shù)據(jù)庫（VIP）、中國生物醫(yī)學(xué)文獻數(shù)據(jù)庫（CMB）、萬方數(shù)據(jù)庫（Wanfang Data）、中國臨床試驗注冊中心、PubMed、Embase、Cochrane Library、Clinical Trials數(shù)據(jù)庫中1999—2020年關(guān)于小兒急性支氣管炎隨機對照臨床試驗（RCT）中英文文獻，對符合納入標(biāo)準(zhǔn)的文獻進行資料提取、分析、歸納，提煉小兒急性支氣管炎臨床試驗設(shè)計與評價的主要技術(shù)要素。結(jié)果 檢索出1 542篇文獻，最終納入19篇RCTs，包括中文17篇、英文2篇。目標(biāo)定位，17項（89.47%）研究的主要目的為改善病情/癥狀，1項（5.26%）為縮短病程，1項（5.26%）以改善中醫(yī)證候為主要目的；試驗總體設(shè)計均采用隨機方法，以雙盲為主的研究14項（73.68%），僅提及使用盲法1項（5.26%），其余4項未提及盲法設(shè)計（21.05%）；采用陽性藥對照14項（73.68%），安慰劑對照5項（26.32%）；多中心研究17項（89.47%）；估算樣本量4項（21.05%）；差異性檢驗設(shè)計15項（78.95%），非劣效檢驗設(shè)計3項（15.79%），優(yōu)效性檢驗1項（5.26%）；全部研究中，具有明確的西醫(yī)診斷標(biāo)準(zhǔn)者16項（84.21%），有明確中醫(yī)診斷與辨證標(biāo)準(zhǔn)者16項（84.21%）；受試者的選擇與退出，全部研究均有納入標(biāo)準(zhǔn)設(shè)計，而有排除標(biāo)準(zhǔn)描述者16項（84.21%）；干預(yù)措施，納入的19項研究中，干預(yù)措施為中成藥的16項（84.21%）、中西藥聯(lián)合應(yīng)用1項（5.26%）和植物藥2項（10.53%），有基礎(chǔ)治療設(shè)計的1項（5.26%）；試驗流程，19項研究均未設(shè)置導(dǎo)入期，設(shè)計隨訪研究1項（5.26%），隨訪時間為3～7 d；療程5～7 d，以5 d為主；有效性評價，19項研究，以疾病有效率/愈顯率、BSS或BSS-ped為主要評價指標(biāo)的有13項（68.42%），以咳嗽、咳痰、氣促/喘息或肺部體征評分為主要評價指標(biāo)的有3項（15.79%），以咳嗽癥狀積分與時間（天）的曲線下面積（AUC）為主要評價指標(biāo)的有1項（5.26%），以中醫(yī)證候有效率為主要評價指標(biāo)1項（5.26%），以主要癥狀（咳嗽、咳痰）基本消失時間為主要評價指標(biāo)1項（5.26%）；安全性評價，19項研究均有安全性指標(biāo)設(shè)計；有2項（10.53%）研究提到試驗質(zhì)量控制；全部研究中，有倫理批件號說明的僅2項（10.53%）。結(jié)論 納入本研究的文獻質(zhì)量高，信息完善，嚴(yán)格遵守循證醫(yī)學(xué)原則，貼近臨床實際，突出中藥特色，研究結(jié)果涵蓋了小兒急性支氣管炎臨床試驗設(shè)計與評價的主要技術(shù)要素，對中成藥治療小兒急性支氣管炎試驗設(shè)計關(guān)鍵環(huán)節(jié)和常見問題進行了分析總結(jié)，具有較高的借鑒價值，為不同文獻之間的結(jié)果比較和系統(tǒng)評價，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 1 542 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.

R287.5

重大新藥創(chuàng)制專項（2020ZX09201-008）