Research On Clinical Application Guideline Of Chinese Patent Medicine For Adult Bronchial Asthma Based On GRADE Systematic Methodology

Objective:Asthma is one of the most common chronic airway diseases in the world.The goal of asthma treatment is to achieve good asthma control.However,complex gene-environment interactions,heterogeneity in clinical presentation,adverse effects of western medicine,and poor compliance make its challenges to achieve.Chinese patent medicines(CPMs)have a long-lasting history in treating asthma and have their superiority.Unfortunately,the misuse of CPMs was common in China.So we developed this guideline to solve the problems of abuse and unreasonable use of CPMs in treating asthma,to standardize and popularize the application of CPMs,to improve the level of asthma control,and promote the generation of high-quality clinical research evidence.Methods:1.Constitution of guideline development group:On the basis of actual condition of Clinical Practice Guideline of traditional medicine/integrated traditional and western medicine and the evaluation of others guideline manuals,the China Association of Traditional Chinese Medicine initiated this guideline and formed a steering committee.The steering committee establish a consensus panel,a consultants' group,and an evidence synthesis team to implement the guideline's progress.2.Topic selection of clinical practice guidelines:Topic selection contains four important and interrelated elements,they are topic,initial scope,clinical question and outcome.This guideline focuses on the clinical advantages of CPMs for adult asthma.The clinical issues of guidelines should be clearly constructed according to the PICO principle.PICO refers to 4 elements,such as population(P),intervention(I),control(C)and outcome(O),which plays a guiding role in the systematic retrieval.A score of 7-9 suggests that the clinical issues were critical,a score of 4-6 suggests that the clinical questions were important,and a score of 1-3 suggests that the clinical problems were not important.Members of the guide team will be graded and effectively ranked.3.Search of CPMs:We searched all CPMs indicated for treating asthma in the National Basic Medical Insurance Drug List,National Essential Drug List,and the Chinese Pharmacopoeia,as well as two drug electronic databases(http://ypk.39.net/,https://db.yaozh.com/).4.Evidence acquisition and systematic review:Three English-language and four Chinese-language databases were searched:MEDLINE,Embase,The Cochrane Library,CNKI,SinoMed(CBM),Wanfang,and VIP database.All databases were searched from their inception until April 30,2019.Manually retrieval resources included textbooks,related published books.Meta-analyses were conducted using RevMan 5.3(Cochrane Collaboration).Considering the particularity of traditional Chinese medicine,we fully considers the CPMs recommended in classical literature and textbooks.Also the decoction of classical Chinese prescriptions were included.5.Grading the quality of evidences:The Grading of Recommendations Assessment,Development,and Evaluation(GRADE)system of rating quality of evidence and grading strength of recommendations were used in this guideline.The highlights including five downgrading factors:risk of bias,indirectness,inconsistency,imprecision and publication bias;and three upgrading factors:large effect,dose-response gradient,opposite confounding.For CPMs with sufficient evidences,GRADE method was adopted to summarize and evaluate the effectiveness and safety.A summary table of evidence and a framework table from evidence to decision-making were developed for consensus panel.For CPMs with insufficient evidence for Meta-analysis,the secretary group shall make a consensus suggestion form,conduct a questionnaire survey through the Delphi method,and form recommendations based on expert consensus.6.Recommended suggestions and consensus:recommended suggestions were proposed based on the results of previously evidence searching,systematic review,and rating quality of evidence by GRADE.Then one or more expert consensus was needed to comprehensively consider the balance of pros and cons,preference and values of patients,and resource investment,so as to obtain the finally recommended suggestions.The Delphi method were used to reach consensus among CPMs which evidence is lacking to support decision-making,especially for CPMs included from TCM ancient books,TCM textbooks,direct experience.Results:1.Evidence-based research:A total of 10 CPMs were assessed for effectiveness and safety(8 CPMs were recommended based on Evidence-based evidence;2 CPMs were recommended based on expert consensus).There were also total of 69 RCTs included eventually.2.Guidelines Recommendations:We formulated eleven recommendations based on evidence synthesis and experts' consensus.For the treatment of uncontrolled asthma,we recommend anti-asthma medications combine with Xiaoqinglong preparations(strong,very low),Danlong oral liquid(strong,moderate),Pingchuan Yiqi granule(weak,low),or Hanchuan Zupa granule(weak,expert consensus).For patients who have poor asthma symptom control,we recommend Chuankezhi injection(weak,very low)and Zhichuanling oral liquid(weak,expert consensus)combine with anti-asthma medications.For patients with intermittent or mild persistent asthma,we recommend Chuankezhi injection or Zhichuanling oral liquid alone(weak,expert consensus).For patients who have good asthma symptom control,we recommend Yupingfeng powder(weak,very low)or Gubenkechuan capsule(weak,low)alone,depending on the manifestations,respectively.Also,we recommend Suhuang Zhike capsule(weak,low)and Sanao tablet(weak,low)combine with anti-asthma medications for cough variant asthma.All the CPMs recommended in the guideline should be used depending on individual patients'manifestations and follow the syndrome differentiation principle.3.Guideline Quality Assessment:The quality of the included studies were low,which seriously affects the level of evidence.Therefore,the quality level of the recommendations in this guideline was low,with only 1 grade B(medium quality),4 grade C(low quality)and 3 grade D(very low quality).The quality of the methodology of the guideline based on AGRE-II tools is high,in which the scope and purpose score is 96.3%,75.9%of Stakeholder Involvement,93.1%of Rigour of Development,100%of Clarity of Presentation,and 16.7%of Applicability and 100%of Editorial Independence.Conclusion:CPMs have great potential in treating asthma.Limited evidence,rely on indirect evidence and expert consensus opinions and low-quality of clinical studies lead to low quality of the recommended opinions in this guideline.Therefore,the recommended opinions in this guideline are of low reliability.More high-quality studies are needed to provide tough evidence in the future.