Research on the development methodology for clinical practice guidelines for organic integration of traditional Chinese and Western medicine.

Integrated traditional Chinese medicine (TCM) and Western medicine (WM) is a new medical science grounded in the knowledge bases of both TCM and WM, which then forms a unique modern medical system in China. Integrated TCM and WM has a long history in China, and has made important achievements in the process of clinical diagnosis and treatment. However, the methodological defects in currently published clinical practice guidelines limit its development. The organic integration of TCM and WM is a deeper integration of TCM and WM. To realize the progression of "integration" to "organic integration", a targeted and standardized guideline development methodology is needed. Therefore, the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts.

[Proposal of Living Evidence-based Guideline for Combination of Traditional Chinese and Western Medicine for Treatment of COVID-19].

In order to standardize the clinical diagnosis and treatment decision-making with traditional Chinese medicine for pa-tients of coronavirus disease 2019(COVID-19) and put the latest clinical study evidence into clinical practice, the international trust-worthy traditional Chinese medicine recommendations( TCM Recs) working group started the compilation of Living Evidence-based Guideline for Combination of Traditional Chinese and Western Medicine for Treatment of COVID-19 on the basis of the standards and re-quirements of WHO handbook, GRADE and RIGHT. This proposal mainly introduces the formulation methods and processes of the living guidelines in details, such as the composition of the working group, the collection and identification of clinical issues and out-comes, the production of the living systematic review and the consensus of recommendations. The guidelines will continue to monitor the clinical study evidences of TCM in the prevention and treatment of COVID-19, and conduct regular evidence updating, retrieval and screening. When there is new study evidence, the steering committee will evaluate the possibility of the evidence to change clinical practice or previous recommendations, so as to decide whether the recommendations for the guidelines shall be implemented or upda-ted. The main criteria considered in the guideline updating are as follows:(1) There are new high-quality randomized controlled trial(RCT) evidences for TCM uninvolved in the previous edition of the guidelines;(2) as for the TCM involved in the guidelines, living sys-tematic review shows that new evidence may change the direction or strength of the existing recommendations. The specific implementation of the living evidence-based guidelines will take this proposal as the study basis and framework, in order to ensure the standardization of the formulation process and methods. This will be the first exploration of the methodology for living guidelines in the field of TCM.

Guidelines on the treatment with integrated traditional Chinese medicine and western medicine for severe coronavirus disease 2019.

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).

Status Quo and Analysis of the Cardiovascular Clinical Practice Guidelines/Expert Consensuses of Chinese and Integrative Medicine: A Systematic Review.

OBJECTIVE: To describe and analyze the status quo of cardiovascular clinical practice guidelines or expert consensuses including both Chinese medicine (CM) and integrative medicine, through systematic literatures searching and quality assessment. METHODS: Data bases including Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, Wanfang Data, China Science and Technology Journal Database were searched for published CM or integrative cardiovascular clinical practice guidelines or expert consensuses. The website www. medlive.cn was also retrieved as supplementary. The clinical practice evaluation tool AGREE II was used to assess the quality of included guidelines or consensuses. RESULTS: A total of 31 relevant clinical practice guidelines or expert consensuses were included, covering diagnosis, treatment, Chinese patent and patient fields. Common cardiovascular diseases like coronary heart diseases, heart failure and arrhythmia were also involved. Through analysis it was found that both the quantity and quality of included guidelines have been improved year by year. A total of 4 evidence-based clinical practice guideline has been found, one of which was a guideline project plan. Except that, the remaining 27 reports were all consensus-based guidelines. The scores of each field, from highest to lowest, were clarity of presentation (58%), scope and purpose (54%), stakeholder involvement (28%), rigor of development (21%), applicability (13%) and editorial independence (8%). CONCLUSIONS: Although clinical practice guidelines in cardiovascular domain of Chinese have gained increasing concern, with both quantity and quality improved, there is still huge gap in methodology and reporting standards between CM guidelines and international ones. On the one hand, it is essential to improve and standardize the methodology of developing CM guidelines. On the other hands, the evaluation system of evidence and recommendation with CM characters should be developed urgently.

Clinical Practice Guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in the Treatment of Rheumatoid Arthritis.

Tripterygium wilfordii Hook F (TwHF) is one of the most commonly used and effective traditional Chinese herbal medicines against rheumatoid arthritis (RA). Both Tripterygium Glycoside Tablets (TGT) and Tripterygium wilfordii Tablets (TWT) are the representative TwHF-based agents enrolled into the 2019 edition of Medicine Catalog for National Basic Medical Insurance, Injury Insurance, and Maternity Insurance. However, individual differences in TGT/TWT response across patients usually exist in the process of treating RA, implying that the clinical application of the two agents may not be standardized leading to the ineffective treatment and the risk of side effects. Growing evidence show that the bioactive constituents of TwHF may often have toxicity, the package insert of TGT and TWT may not be described in detail, and the therapeutic windows of the two agents are narrow. Thus, it is an urgent task to develop a standardized clinical practice guideline for TGT and TWT in the treatment of RA. In the current study, a group of clinical experts of traditional Chinese medicine and Western medicine in the research field of rheumatism diseases, pharmacists, and methodologists of evidence-based medicine were invited to select the clinical questions, to determine the levels of the evidence and the strength of the recommendations, and to develop the recommendations and good practice points. The guideline is formed based on the combination of clinical research evidence and expert experience (evidence-based, consensus, supplemented by experience). The clinical problems which are supported by clinical evidence may form recommendations, and the clinical problems without clinical evidence may form experts' suggestions. Both recommendations and experts' suggestions in this guideline summarized the clinical indications, usage, dosage, combined medication, and safety of TGT and TWT against RA systematically and comprehensively, which may offer a professional guidance in the context of the clinical application of the two TwHF-based agents.

[Expert consensus statement on Kangfu Xiaoyan Suppository in treatment of pelvic inflammatory in clinical practice].

Kangfu Xiaoyan Suppository is widely used in the treatment of gynecological inflammatory diseases. Long-term clinical application and a certain amount of research evidences show that Kangfu Xiaoyan Suppository can alleviate the clinical symptoms of pelvic inflammatory diseases,reduce the recurrence rate,and relieve sequelae,with a better safety and economic characteristics. As a type of nationally protected traditional Chinese medicine and type B medicine included in medical insurance,it has been selected as a Chinese patent medicine for rectal administration. It was included in the Guidelines for diagnosis and treatment of common gynecological diseases of traditional Chinese medicine published by the Chinese Academy of Traditional Chinese Medicine in 2012,the Pelvic inflammatory diseases diagnosis and treatment guidelines issued by the Infectious Diseases Collaborative Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association in 2014,and the group standard of Single use of traditional Chinese medicine/combined antibiot guidelines for clinical practice-pelvic inflammatory diseases of the Chinese Academy of Traditional Chinese Medicine in 2017. To further enhance clinicians' understanding of the drug and better guide its rational clinical use,experts from the field of gynecology of traditional Chinese and Western medicine were invited to develop and compile this expert consensus. This consensus takes full account of clinical evidences and expert clinical experience,and form recommendations for clinical problems based on evidences and consensus recommendations for clinical problems without evidence by nominal grouping method. The expert consensus is mainly formed in the consideration of six factors: quality of evidence,economy,efficacy,adverse reactions,patient acceptability and others. Based on clinical research evidences and expert experience,this consensus provides a preliminary reference for the clinical use of the drug in a concise and clear format. However,evidence-based support is still required in a large number of high-quality studies,and this consensus will be revised in the future according to new clinical problems and the update of evidence-based evidence in practical application.

[Technical specification of expert consensus statement in developing clinical practice guidelines of traditional Chinese medicine].

The formation of expert consensus statement is an indispensable part in the process of developing clinical practice guidelines. The Guidelines International Network believes that experts make group decisions for different stages and issues,and the process of gathering expert opinions is the process of reaching the consensus. GRADE system also requires that recommendations should be formed based on expert consensus in consideration of the risk and bias,patients' preferences and values,resources and other factors. At present,the main method for reaching consensus is the formal consensus method. According to the published clinical guidelines,most of them failed to report the specific methods and process of reaching expert consensus. Therefore,it is impossible to obtain an objective evaluation. This phenomenon is more common in the field of clinical practice guidelines of traditional Chinese medicine( TCM). There are two main reasons for this phenomenon. For one thing,the developers of the guidelines neglect the importance of transparency and objectivity in the implementation of expert consensus. For another,they know little about the methods and technical specifications for the formation of expert consensus. To solve them,based on the internationally recognized consensus-building methods,as well as the specific stages in the process of developing clinical practice guidelines of traditional Chinese medicine,it is of great significance to put forward the technical norms for TCM researchers to develop the expert consensus. This guide will provide detailed guidance for forming the expert consensus for TCM clinical practice guideline. This guideline has been approved and published by the Chinese Association of Traditional Chinese Medicine( No. T/CACM 1049-2017).

[Expert consensus statement on Diemailing~® Kudiezi Injection in clinical practice].

Diemailing~® Kudiezi Injection( DKI) is widely used in the treatment of cerebral infarction,coronary heart disease and angina pectoris. Long-term clinical application and related research evidence showed that DKI has a good effect in improving the clinical symptoms of cardiovascular and cerebrovascular diseases. However,this injection has not been included in any clinical practice guideline. It has been found that the use of DKI is in wrong way in clinical practice in recent years. Therefore,clinical experts from the field of cardiovascular and cerebrovascular diseases nationwide are invited to compile this expert consensus in order to guide clinicians.GRADE system is used to grade the quality of evidence according to different outcomes according to degrading factors. Then it forms the recommendation or consensus suggestion through the nominal group method. The formation of expert consensus mainly considers six factors: quality of evidence,economy,efficacy,adverse reactions,patient acceptability and others. Based on these six aspects,if the evidence is sufficient,a " recommendation" supported by evidence is formed,and GRADE grid voting rule is adopted. If the evidence is insufficient,a " consensus suggestions" will be formed,using the majority voting rule. In this consensus,the clinical indications,efficacy,safety evidences and related preliminary data of DKI were systematically and comprehensively summarized in a concise and clear format,which could provide valuable reference for the clinical use of DKI. This consensus has been approved by China association of Chinese medicine which is numbered GS/CACM 202-2019.

Toward Evidence-Based Chinese Medicine: Status Quo, Opportunities and Challenges.

How to test the treatments of Chinese medicine (CM) and make them more widely accepted by practitioners of Western medicine and the international healthcare community is a major concern for practitioners and researchers of CM. For centuries, various approaches have been used to identify and measure the efficacy and safety of CM. However, the high-quality evidence related to CM that produced in China is still rare. Over the recent years, evidence-based medicine (EBM) has been increasingly applied to CM, strengthening its theoretical basis. This paper reviews the past and present state of CM, analyzes the status quo, challenges and opportunities of basic research, clinical trials, systematic reviews, clinical practice guidelines and clinical pathways and evidence-based education developed or conducted in China, pointing out how EBM can help to make CM more widely used and recognized worldwide.

Reporting characteristics of case reports of acupuncture therapy with CARE guidelines.

OBJECTIVE: To investigate the reporting characteristics of case reports of acupuncture therapy with CAse Report (CARE) guidelines, and to explore the applicability of the guidelines for these case reports. METHODS: Case reports published from January 1, 2011 to December 31, 2013, were identified by searching PubMed and the China Biomedicine Database by using MeSH terms. Screening and data extraction of case reports were conducted by two independent researchers. Assessments based on CARE guidelines and data analysis were conducted by using Excel 2003 and RevMan 5.0. RESULTS: A total of 61 case reports published in 19 journals were identified, which involved 16 major types of diseases. Fifteen (24.6%) case reports declared no conflict of interests, and 5 (8.2%) reported funding sources. None of these case reports met all items of CARE guidelines, and only 6 subordinate items were fully reported among 50% of the case reports. Subgroup analysis indicated that case reports published in English or those that did not have competing interests had higher reporting quality. CONCLUSIONS: The reporting quality of case reports of acupuncture therapy is rather low. The reason might be a lack of awareness among authors and the poor dissemination of information regarding CARE guidelines in China. More evaluation studies are needed to promote and improve adherence to CARE guidelines. Moreover, an extended version of CARE guidelines should be developed for cases reports of special interventions such as acupuncture or adverse events caused by interventions.

[Analysis of reporting specification about sepsis practice guideline based on RIGHT standard].

At present, the study of clinical practice guide focuses on the quality of the guide, but not enough attention to the reporting standards of the practice guide, so how to standardize the report is an urgent problem in the field of evidence-based medicine. This paper uses the latest practice guidance reporting tool RIGHT standard, analyzes the latest two sepsis practice guidelines at home and abroad, and found that there are few problems in the basic information, recommendations and other information in 7 major areas, and many deficiencies in background, evidence, review and quality assurance, funding and declaration and management of interests, in particular, domestic guidance. We hope that the researchers will use the RIGHT standard to develop new guidelines for sepsis or other areas, standardize the report of the guide, especially the writing of traditional Chinese medicine guide, should reflect the characteristics of traditional Chinese medicine.

[Methodological quality assessment of community-acquired pneumonia clinical practice guidelines in China based on AGREE â ¡ tool].

This study is aimed to identify and assess the methodological quality of community-acquired pneumonia (CAP) clinical practice guidelines (CPG) in China by using AGREE Ⅱ tool. CNKI, SinoMed, Wanfang, and VIP Chinese databases from database establishment to March 2017 were searched by manual retrieval to collect all the clinical practice guidelines prepared by various associations or organizations, then AGREE Ⅱtool was used to assess them. Data in each CPG were analyzed in terms of six domains, including scope and purpose, participants, rigor, clarity and readability, applicability and editorial independence. A total of 4 CPGs were included. The results showed that the scope and purpose scored 45.8%; the clarity of expression scored 44.75%; the participants scored 31.9%; the rigor scored 18.98%; the applicability scored 7%; and finally the editorial independence scored 1%. It is concluded that the quality of applicability and the editorial independence should attained paid more attention in future development or updating of the guidelines. In addition to strengthening the compliance with international general principles, we should also pay attention to the characteristics of traditional Chinese medicine treatment, especially the related evidences as complementary and alternative treatment for western intervention measures.

Quality assessment of clinical practice guidelines for integrative medicine in China: A systematic review.

OBJECTIVE: To assess the quality of integrative medicine clinical practice guidelines (CPGs) published before 2014. METHODS: A systematic search of the scientific literature published before 2014 was conducted to select integrative medicine CPGs. Four major Chinese integrated databases and one guideline database were searched: the Chinese Biomedical Literature Database (CBM), the China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Data, and the China Guideline Clearinghouse (CGC). Four reviewers independently assessed the quality of the included guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE) II Instrument. Overall consensus among the reviewers was assessed using the intra-class correlation coefficient (ICC). RESULTS: A total of 41 guidelines published from 2003 to 2014 were included. The overall consensus among the reviewers was good [ICC: 0.928; 95% confifi dence interval (CI): 0.920 to 0.935]. The scores on the 6 AGREE domains were: 17% for scope and purpose (range: 6% to 32%), 11% for stakeholder involvement (range: 0 to 24%), 10% for rigor of development (range: 3% to 22%), 39% for clarity and presentation (range: 25% to 64%), 11% for applicability (range: 4% to 24%), and 1% for editorial independence (range: 0 to 15%). CONCLUSIONS: The quality of integrative medicine CPGs was low, the development of integrative medicine CPGs should be guided by systematic methodology. More emphasis should be placed on multi-disciplinary guideline development groups, quality of evidence, management of funding and conflfl icts of interest, and guideline updates in the process of developing integrative medicine CPGs in China.

The quality of evidence in Chinese meta-analyses needs to be improved.

OBJECTIVES: We conducted a systematic review using GRADE (Grading of Recommendations Assessment, Development and Evaluation) system to assess the quality of evidence of Chinese meta-analyses (MAs). DESIGN/SETTING: A systematic review of MAs listed in Chinese Biomedicine Literature Database from January 2010 to December 2012. METHODS: Mesh term "meta-analysis" was used to search the Chinese Biomedicine Literature Database from January 2010 to December 2012. Characteristics and main outcomes of each included MA were extracted, and the GRADE system was used to assess the quality of evidence for each outcome. A 10% random sample of Cochrane MAs between 2010 and 2012 was also assessed as control group. RESULTS: A total of 564 Chinese MAs (including 1,237 main outcomes) and 95 Cochrane MAs (including 251 main outcomes) were identified. Almost half (600, 48.5%) of the outcomes in Chinese MAs were rated as low, and the proportion of outcomes with high or moderate quality of evidence was lower in Chinese MAs than Cochrane MAs (Chinese, 406 [32.8%] vs. Cochrane MAs, 155 [61.8%], P < 0.001). Of the outcomes in Chinese MAs, 1,012 (81.8%) were downgraded for risk of bias. Other common factors for downgrading were imprecision (448, 36.2%), publication bias (418, 33.8%), inconsistency (351, 28.4%), and indirectness (1, 0.1%). CONCLUSIONS: Chinese MAs were of low quality of evidence. Risk of bias, inconsistency, and publication bias were the three most common downgrade factors in Chinese MAs. Efforts must be made to improve quality of evidence of Chinese MAs, and a call for more rigorous training of investigators in China is warranted.

Surgery combined with intraoperative hyperthermic intraperitoneal chemotherapy (IHIC) for gastric cancer: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Adjuvant intraoperative hyperthermic intraperitoneal chemotherapy (IHIC) is a therapy which combines thermotherapy and intraperitoneal chemotherapy. It is theoretically powerful for patients with advanced gastric cancer (AGC), but is there evident advantage in clinical practice? We need evidence to guide our decision-making. OBJECTIVES: Meta-analysis was performed to assess the effectiveness and safety of adjuvant intraoperative hyperthermic intraperitoneal chemotherapy (IHIC) for patients with resectable locally advanced gastric cancer, and to provide the reference for clinical practice and study. METHODS: We searched the Cochrane Library, PubMed, Embase, Web of Science and Chinese databases (Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI) and Wanfang) electronically and also retrieved papers from other sources (tracing related references and communication with other authors). All relevant randomised controlled trials (RCTs) were collected to compare surgery combined with IHIC to surgery without IHIC for AGC. There were no language restrictions. After independent quality assessment and data extraction by two reviewers, meta-analysis was conducted by RevMan 5.1 software. RESULTS: 16 RCTs involving 1,906 patients were included. Compared with surgery alone, combination therapy (surgery plus IHIC) was associated with a significant improvement in survival rate at 1 year (hazard ratio (HR) = 2.99; 95% confidence interval (CI) = 2.21 to 4.05; p < 0.00001), 2 years (HR = 2.43; 95%CI = 1.81 to 3.26; p < 0.00001), 3 years (HR = 2.63; 95%CI = 2.17 to 3.20; p < 0.00001), 5 years (HR = 2.49; 95%CI = 1.97 to 3.14; p < 0.00001), and 9 years (HR = 2.14; 95%CI = 1.38 to 3.32; p = 0.0007). Compared with surgery alone, combination therapy was associated with a significant reduction in recurrence rate at 2 years (RR = 0.42; 95%CI = 0.29 to 0.61; p < 0.00001), 3 years (RR = 0.35; 95%CI = 0.24 to 0.51; p < 0.00001) and 5 years (RR = 0.47; 95%CI = 0.39 to 0.56; p < 0.00001). IHIC was not found to be associated with higher risks of anastomotic leakage, ileus, bowel perforation, myelosuppression, gastrointestinal reaction and hypohepatia, but it increased the incidence of abdominal pain (RR = 21.46; 95%CI = 5.24 to 87.78; p < 0.00001). CONCLUSIONS: Compared with surgery alone, surgery combined with IHIC can improve survival rate and reduce the recurrence rate, with acceptable safety. However, safety outcomes should be further evaluated by larger samples and high quality studies. Additionally, hyperthermia for the intraperitoneal chemotherapy needs more clinical research.