| Objective: To study the design elements of clinical randomized controlled trials of drugs for allergic rhinitis(AR)in children,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,according to Chinese and English key words,we searched in China National Knowledge Infrastructure(CNKI),China Science and Technology Journal Database(VIP),Wan fang Database(WF),China Biomedical Literature Database(CMB),China Clinical Trials Registration Center,Pub Med,EMBASE,Cochrane Library,Clinical trials et al.Published randomized controlled trials(RCTs)of drugs for AR in children from the establishment of the database to August 2020,we extracted,analyzed and summarized the literature that met the inclusion criteria,and extracted the main technical elements of the design and evaluation of clinical trials of drugs for AR in children;Referring to the Cochrane Collaboration Network System evaluator manual,the method of literature inclusion was developed,and all the retrieved literatures were imported into the Note Express document management software for duplicate checking,The repetitive literatures were eliminated,the remaining literature titles and abstracts were read,and the literatures that did not meet the requirements were excluded.The full text of relevant literatures was downloaded and read,and the literatures that did not meet the inclusion criteria were excluded.Finally,the literatures that met the inclusion and exclusion criteria and improved Jadad scale were included,with the scores of domestic literatures ≥ 3 and foreign literatures ≥ 4;The included literatures were required to meet the diagnostic criteria of allergic rhinitis.The intervention measures were drugs(traditional Chinese medicine or chemical drugs)and immunotherapy(sublingual / subcutaneous),and the languages were Chinese or English;Data extraction was carried out for the included literatures,including the title,author,experimental design(randomized,controlled,blind,multicenter,etc.),diagnostic criteria,syndrome differentiation criteria,inclusion criteria,exclusion criteria,intervention measures,course of treatment,introduction period and follow-up,effectiveness evaluation index and safety evaluation index(observation index,evaluation time point,evaluation tool,index measurement method and definition),etc.Results: A total of 2735 articles were retrieved,and 18 were included,including 5 in Chinese and 13 in English.A total of 10 aspects of clinical trial design and evaluation techniques for children with allergic rhinitis were extracted as follows:(1)In all studies,no matter short-term or long-term treatment,the clinical orientation was to relieve nasal symptoms.(2)The overall design of the trial was randomized.The choice of control drugs was mainly placebo-controlled 10 items(55.57%),positive drug control 6 items(33.33%),the rest were three arm trial design 2 items(11.11%);All the studies were double-blind and 12(66.67%)were included;There were 11 multicenter studies(61.11%)and 8 sample size estimates(44.44%).(3)According to the diagnostic criteria,all 18 items met the diagnostic criteria of AR in children,and one of them met the diagnostic criteria of traditional Chinese medicine,which was the "Chinese medicine industry standard of the people’s Republic of China diagnostic and curative effect standard of TCM syndrome",accounting for 33.3% of the literature on TCM treatment;There were 8 items(44.44%)with clear diagnostic criteria of Western medicine,2 items(25%)of which were respectively referred to "guidelines for the diagnosis and treatment of allergic rhinitis in children" and "ARIA guidelines",There were 1item in zhufutang Practical Pediatrics,1 item in diagnostic criteria and efficacy evaluation criteria for allergic rhinitis(revised in 1997,Haikou),1 item in Japanese practical guidelines for the treatment of allergic rhinitis(2013),1 item in Japanese AR guidelines(2017)(12.5%),10 items(55.56%)were not specified,but the subjects were required to meet the clinical characteristics of AR diagnosis in children;There was no definite diagnostic standard of TCM syndrome differentiation in all the studies.(4)All the studies had clear inclusion criteria and exclusion criteria design,4 had rejection criteria design,15 had rejection case description.In the design of inclusion criteria,all 18 items(100%)met the diagnostic criteria of AR in children,13 items(72.22%)were limited in age,11 items(61.11%)were required in course of disease,14 items(77.78%)were limited in positive results of allergen test,and 9items(50%)were specified in severity of disease,Informed consent was signed for all studies;The exclusion criteria included 11 diseases(61.11%)that needed to be differentiated from AR,14 items(77.78%)of organic lesions in the nasal cavity and respiratory tract,5 items(27.78%)with specific immunotherapy history,11 items(61.11%)severe systemic chronic diseases,and15 items(83.33%)drugs and washout period affecting baseline;There were 4 items(22.22%)of standard design,15 items(83.33%)of case description,and 1 item(5.56%)completed the study.(5)The intervention measures included intranasal corticosteroids and antihistamines(each 5 items,27.78%),combined traditional Chinese and Western medicine and sublingual immunotherapy(each 3 items,16.67%),oral corticosteroids and antihistamines(1 item,5.56%)and nasal cellulose powder(1 item,5.56%).The course of treatment ranged from 1week 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.(6)In all studies,8(44.44%)designed the lead-in period,which lasted for 3 days to 3 weeks,and 10(55.56%)designed the follow-up period of 1 week to 6 months.(7)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%),T4 SS,NSS,TSSC,DSS 1 item(5.56%),or3 TNSS,4TNSS,TOSS 1 item(5.56%).(8)Safety indicators: 17 items(94.44%)designed adverse events or adverse reactions,and one or more of joint laboratory examination indicators,otorhinolaryngology special examination and vital signs examination were used as common safety evaluation indicators.(9)There was no description of test quality control in all studies.(10)All the studies had 8 ethical approval numbers(44.44%).Conclusion: The research group systematically searched the clinical trials of AR drugs in children published in domestic and foreign journals from the establishment of the database to August 2020.The included literatures are scientific in design,complete in technical points of design and evaluation,and of high quality.The research results cover the main technical elements of clinical trials design and evaluation of pediatric AR traditional Chinese medicine in children under the mode of combination of disease and syndrome,which has a high reference value and provides a literature basis for the formulation of the technical guidelines for the design and evaluation of Chinese medicine clinical trials in children with allergic rhinitis(standardization project of Chinese society of traditional Chinese medicine,approved in June 2017). |
