| ObjectiveFollowing the principle of "mainly referred to evidence-based results,supported by expert consensus,learned from expert experience",used GRADE methodology to study and prepare the clinical application guidelines of Chinese patent medicine in the treatment of climacteric syndrome,so as to provide the principles and guidance for the selection of Chinese patent medicine for clinical front-line western medicine,traditional Chinese medicine,integrated traditional Chinese and Western medicine specialists and grass-roots hospital doctors in the treatment of climacteric syndrome,improve the clinical efficacy of Chinese patent medicine in the treatment of climacteric syndrome and avoid unreasonable drug use.Methods1.A working group was established and began to carry out the guidelines research and preparation.At the same time,an expert advisory group of the guidelines standardization project was established to conduct the questionnaire survey and consensus meeting later.2.After investigation,the ranking of clinical problems and outcome indicators of this guidelines were determined.Search and select Chinese patent medicines for the treatment of climacteric syndrome in China.According to PICOs,the inclusion and exclusion criteria of literature were determined,the literature retrieval strategy was formulated,and the literature research was carried out.The included literatures were evaluated by methodology,comprehensive analysis of evidence and GRADE evidence quality evaluation.3.Two rounds of Delphi questionnaire survey were conduct and expert consensus meetings were held to the finally determination of the recommended drugs in the guidelines and the GRADE recommendation level of each drug.4.According to the recommend medicines in the finalized guidelines,the consensus meeting refined the usage,dosage,safety,precautions,etc.of the recommended medicines in the guidelines.After that,the experts of traditional Chinese medicine wrote the first draft of the recommendation,and then submitted it to the experts of Western medicine for review.Combined with the feedback of Western medicine experts,the first draft of the guidelines were written.5.After the expert internal audit meeting held by the Standardization Project Office of Traditional Chinese Medicine Association,the guidelines were revised according to the requirements of the Standardization Office and the opinions of internal audit experts,and finally the final draft of the guidelines were issued.Results1.The guidelines working group was established at the project start meeting.The working group was composed of clinical experts of Chinese and Western medicine,pharmaceutical experts,methodologists and subject secretaries.The working group consists of 15 people.The proportion of Chinese and Western medicine was about 1:1.2.A total of 30 clinical experts of traditional Chinese and Western medicine were consulted through the experts questionnaire survey on the construction of clinical problems and the importance ranking of outcome indicators.Clinical problem items with a support rate greater than or equal to 60%were included as identified clinical problems.Finally,there were three clinical problems included in the study:whether it is effective and safe to treat climacteric syndrome with Chinese patent medicine alone?In the treatment of climacteric syndrome,under what circumstances do we need Chinese patent medicine combined with western medicine;and can Chinese patent medicine reduce the side effects of Western medicine?Whether Chinese patent medicine can prevent and treat postmenopausal related diseases(cardiovascular disease,osteoporosis,Alzheimer’s disease,etc.).The third clinical question could not be answered in this version of the guidelines because there was no evidence-based evidence.The final outcome index items with a support rate greater than or equal to 60%were included as the final outcome index,and the importance ranking of the final outcome index was determined according to the average score of the importance score of each outcome index.The final included outcome indicators included:key outcome indicators(Kupperman score,MRS score,MENQOL score),important outcome indicators(SAS score,SDS score,PSQI score,incidence of adverse reactions,endometrial thickness),and not important outcome indicators(sex hormone level,liver and kidney function,blood lipid level).3.Through internet search,57 Chinese patent medicines were selected.After excluding illegally sold and discontinued Chinese patent medicines,38 Chinese patent medicines were finally met the inclusion criteria.4.Literature search results:a total of 23500 literatures were obtained.The finally included literatures covered 15 kinds of Chinese patent medicines,including 53 articles of Kuntai Capsule,7 articles of Kunbao pill,2 articles of Jiarong tablet,2 articles of Gengnian an,1 article of Dizhen granule,2 articles of Linglianhua granule,2 articles of Ciwujia injection,2 articles of Xiangshao granule,2 articles of Yikunning,1 article of compound Difu oral liquid,1 article of Longfengbao tablet,1 article of Tiangui Gengnian soft capsule,1 article of Gengnianshu tablet,1 article of Chang’e Jiali pill and 1 article of Jieyu Anshen granule.5.Literature evidence GRADE evaluation results:The studies of 3 Chinese patent medicines such as Kuntai Capsule and linglianhua granule were judged as medium quality evidence;the studies of 6 Chinese patent medicines such as Kunbao pill and Jiarong tablet were judged as low-quality evidence;The studies of six Chinese patent medicines such as Gengnian’an and Dizhen granules were judged as very low-quality evidence.The main meta-analysis results of related Chinese patent medicines are as follows:(1)Kuntai Capsule:Kupperman score after 3 mouths of Kuntai Capsule vs hormone treatment,it suggested that the curative effects of the two groups were equivalent(20 studies with 1769 cases,MD=-0.19,95%CI:[-0.49,0.12]).Kupperman score after the treatment of Kuntai Capsule+ hormone vs hormone showed that the combined group was better than the hormone group(8 studies with 760 cases,MD＝-4.61,95%CI:[－5.45,3.77]).(2)Kunbao pill:the comparison of Kupperman score after Kunbao pill vs hormone treatment showed that the curative effects of the two groups were equivalent(2 studies with 101 cases,MD=1.38,95%CI:[-1.90,4.66]).The effective rate of Kunbao pill+hormone vs hormone treatment suggested that the combined group was better than the hormone group(2 studies with 142 cases,RR=1.18,95%CI:[1.03,1.34]).(3)Linglianhua Granule:the change of Kupperman score after Linglianhua granule vs Kuntai Capsule treatment suggested that the curative effects of the two groups were equivalent(1 studies with 234 cases,MD=-1.50,95%CI:[-3.20,0.20]).(4)Jiarong tablet:the change of Kupperman score after Jiarong tablet vs hormone treatment suggested that the curative effects of the two groups were equivalent(1 studies with 150 cases,MD=-0.45,95%CI:[-2.63,1.73]).(5)Gengnian:the effective rate after Gengnian vs hormone treatment indicated that the two groups had the same curative effect(1 studies with 75 cases,RR=1.18,95%CI:[0.95,1.45]).(6)Dizhen Granule:the effective rate of Dizhen granule+tibolone vs tibolone suggested that the combined group was better than tibolone group(1 studies with 120 cases,RR=1.84,95%CI:[1.43,2.36]).6.Determination of GRADE recommendation level:The statistical results of two rounds of Delphi questionnaire suggested that the preliminarily recommended Chinese patent medicines are Kuntai Capsule,Kunbao pill,Jiarong tablet,Gengnian’an and Dizhen granules.After several rounds of expert consensus meetings,it was finally determined that the recommended Chinese patent medicines and their recommendation levels are as follows:Kuntai Capsule and linglianhua granule were strong recommendations;Kunbao pill,Jiarong tablet,Gengnian’an capsule and Dizhen granule were weakly recommended,Other patent Chinese medicines had not reached a consensus and were not included in the recommendations of this guideline.7.Detailed recommendations of the guideline:the usage and dosage,medication course,medication precautions and other contents of the recommended Chinese patent medicines in the guideline were finally determined through the consensus of the expert consensus meeting.Finally,after the review and feedback of Western medicine experts and repeated revision,the pass rate of Western medicine experts was 100%.According to the opinions put forward by Chinese and Western medicine experts of the consulting group,the first draft of the guideline was written after the description of specific recommendations revised.8.The guidelines were submited to experts for internal review,and were finally submit for release.ConclusionIn this study,the GRADE guidelines methodology was used to formulate the first version of clinical application guidelines of Chinese patent medicine in the treatment of climacteric syndrome.The guidelines were published in 2021 and popularized throughout the country.This guidelines provided western gynecologists and general practitioners with clear guidelines with definite curative effect and high safety for the rational use of Chinese patent medicine in the treatment of climacteric syndrome,so as to reduce the risk of unreasonable drug use.This guidelines were suitable for clinical promotion. |
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