Evidence-based Chinese medicine (EBCM) is one of the innovative achievements in the development of evidence-based medicine (EBM) in China. The EBCM has made initial progress: the evidence-based scientific decision-making model has become popular; a series of key technologies for evidence-based evaluation and research of traditional Chinese medicine (TCM) have been established; several technical specifications have been formulated in line with international standards; clinical evidence database of TCM has been established; a number of high quality clinical trials have been published in internationally renowned journals; and the International Forum on Evidence based Chinese Medicine(EBCM) has become a brand conference. Difficulties in EBCM development mainly involve: lack of high quality clinical evidence, difficulty in producing evidence, and decentralization of research team. Based on opportunities and challenges of the development of TCM, this article proposed the short-term and long-term goals, implementation paths and five key directions for the development of EBCM in the future, and puts forward three suggestions for further development of EBCM.
Objectives To systematically evaluate the clinical characteristics of adverse drug reactions (ADRs) caused by Shuanghuanglian Injection (SHLI) and to provide reference for post-market evaluation and clinical application of SHLI. Methods We searched electronic databases such as the Chinese National Knowledge Infrastructure (CNKI, 1979.1-2009.9), the Chinese Science and Technology Journal Full-text Database (VIP, 1989.1-2009.9), and the Chinese Biomedical Disc (CBMdisc, 1978.1-2009.9). ADR cases were analyzed according to occurrences categorized. Available data was assessed using the Chi-square test including relative ratios (RR) with 95% confidence intervals (95%CI). Different medicine combinations and comparisons between SHL powder injection and SHL injection were calculated using the statistical software Stata 9.1. Results (1) A total of 452 articles were included with a total of 2 799 ADR cases reported. Case reports were the main design type of included literature, which accounted for 84.51%. According to 31165 cases of SHLI treatment and 1 013 corresponding ADRs, the incidence of SHLI ADR was calculated as 3.25%. (2) The ratio of male to female in the reported ADR cases was 1.13?1. (3) Allergy to Penicillin, which accounted for 13.38% of the total cases, was at the top for past allergic history, followed by sulfonamides and asthma (2.68%). (4) In terms of disease treated respiratory disease accounted for 91.75% of all cases of SHLI ADRs, followed by digestive diseases (5.17%), and urinary diseases (1.11%). (5) Penicillins were the most common combination choice with SHLI, and such combination showed higher ADR risk than SHLI used alone [RR=3.14, 95%CI (2.58, 3.81)]. (6) Multiple systems/organs were involved in SHLI ADRs, and were ranked downwards according to proportion as: skin, digestive system, general reactions, respiratory system, nervous system, cardiovascular system, local reactions, urinary system, hematologic system and others. (7) According to the WHO ADR Classification Criteria, ADR cases were divided into four grades. There were 6.36%, 5.48%, 45.62%, and 2.12% cases of Grade Ⅰ, Ⅱ, Ⅲ and Ⅳ , respectively. And the prognoses of the rest 52.42% cases were reported unclearly. (8) All cases of death were caused by allergic shock, except for one, which was caused by myocardial infarction induced by pain at the injection site. The fastest ADR case occurred 1 minute after being injected. (9) There was a remarkable difference (Plt;0.05) in the rate of ADR caused by SHLI in power form (2.25%) and as a solution (4.14%). Conclusion The clinical manifestations of ADRs caused by SHLI mainly include skin allergic reactions and gastrointestinal reactions. There is an increased risk of ADR induced by combined uses of SHLI and other drugs, especially antibiotics. Compared to the solution, the powder has lower ADR occurrence and higher safety with statistical significance. We propose strengthening management and surveillance on SHLI from manufacturing to application, and improving the level of the risk management for post-market drugs.
With the advancement of modern research in traditional Chinese medicine (TCM), evidence regarding the clinical efficacy and mechanisms of action of TCM has rapidly accumulated. However, due to a lack of methodological safeguards, the disconnection between clinical and basic research in TCM has become increasingly prominent, making it difficult to form an evidence chain that supports the scientific value of TCM in a manner that is "clear and understandable". Therefore, it is necessary to develop methods for the translation and integration of clinical and basic research evidence oriented towards clinical value, to form a reliable evidence chain that can further discover patterns, confirm efficacy, and highlight advantages. This article discusses the construction and evaluation methods of the evidence chain for the efficacy of TCM, aiming to provide theoretical and methodological references for related work.
Inconsistency, impracticability and non-standardization of the selection, measurement and reporting of outcomes are three primary existing issues in clinical trials. These problems pose a threat to huge research waste when the results of similar studies are not able to be combined or compared. The key for resolution will be to standardize outcomes in traditional Chinese medicine (TCM) clinical trials and to establish a core outcome set (COS), which is a set of outcomes to be reported as a minimum in all TCM clinical trials of similar healthcare system and syndromes. The first step in the development of COS is to collect all existing outcomes, that is, to build a pool of outcomes for clinical trials of TCM. A pool of outcome is the basis of developing COS, which is important to follow strict and scientific methodology. This paper aims to construct an outcome pool from published literature, clinical trial registration protocols, and clinicians, and patients questionnaires were used to form a list of outcomes. In addition, the influencing factors of constructing an outcome pool and considerations for each problem are summarized in order to provide guidance and reference for the development of COS in clinical trials for TCM.
To aim directly at the individualized character and tendency about clinical assessment of Traditional Chinese Medicine (TCM), we draw off a new pathway which is evidence-based goal attainment scale(EBGAS) in the text. i.e., we will develop clinical individualized assessment method of TCM on account of GAS by the approach of evidence based medicine.
Objectives We conducted a literature review of 33 kinds of Traditional Chinese medicine injections (CMIs) on the national essential medicine list (2004 edition) of China in ADR articles to retrieve basic ADR information and research trends related to CMIs and to provide evidence for the research and development as well as the rational use of CMIs, particularly pharmacovigilance and risk management of CMIs. Methods We electronically searched Chinese Biomedical Literature Database (CBM, Jan. 1978-April 2009), the China National Knowledge Infrastructure Database (CNKI, Jan. 1979-April 2009), Chinese Science and Technology Periodical Database (VIP, Jan. 1989-April 2009) and the Traditional Chinese Medicine Database (Jan. 1984 April 2009). We also retrieved the websites of Ministry of Health and State Food and Drug Administration, to collect data about CMIs ADRs reports and regulations from “Newsletter of Adverse Drug Reactions” (Issue 1 to 22). Then we descriptively analyzed all the results on the year published, periodicals and types of study design of included ADR literatures, the major CMIs as well as the regulations about their ADRs. Results (1) There were 5 405 citations found in total and 2160 were removed because of duplication. After screening the title, abstract and full text of the selected papers, 1 010 studies finally met the eligible criteria. (2) The total and cumulative amount of research articles published about CMIs ADRs significantly increases over time. (3) The included 1,010 articles were scattered among 297 periodicals. A total of 55 journals on pharmaceutical medicine, containing 399 articles, accounted for 39.50% of total; 64 journals on traditional Chinese medicine and pharmaceutical medicine, containing only 197 articles, amounted for 19.50% of total. Only 22 periodicals were included on the core journals of the Beijing University List (2008 edition) (8.94% of the total journals in the list), which published 129 articles (12.77% of the total articles published). (4) We categorized the articles included into eight categories based on their content and study methodology. There were: 348 case reports and 254 case series which accounted for 34.46% and 25.15% of the total articles, 119 overviews (11.78%), 116 randomized controlled trials (11.49%), 78 cross-sectional studies (7.72%), 61 ADR literature analyses (6.04%), and 28 non-randomized controlled clinical studies (2.77%). (5) In the three of top ten journals, "Adverse Drug Reactions Journal", "China Medical Herald", and "Chinese Pharmaceuticals" published literature accounted for 5.84%, 3.76% and 2.67% of the total respectively. (6) The reports of ADRs to Shuanghuanglian, Qingkailing and Yuxingcao injections were the most in all reports for CMIs (All the three injections had more than 200 articles, accounting for 41.95% of the total). The Ministry of Health and the State Food and Drug Administration took measures to supervise them. (7) The four kinds of CMIs (Shuanghuanglian, Ciwujia, Yuxingcao, and Yinzhihuang injections) among the top 5 reported ADR literatures were removed from the market or were suspended for sale. The varieties and numbers of reports for CMIs ADRs have relationship with the supervision to them. Conclusions (1) Articles published on CMIs ADRs increased year by year, but overall the research is of low quality and is scattered in a large number of sources. (2) It is very urgent to create a clear standard to grade ADRs of CMIs for the risk management. (3) It is necessary to enforce safety re-evaluation work for CMIs and to promote the clinical rational use.
Based on evidence-based medicine (EBM) and from the viewpoint of providing scientific evidence for clinical application, we found that Traditional Chinese Medicine (TCM) was short of adequate evidence to support its therapeutic effects due to lack of high quality clinical research. Data management plays a very important role in clinical research. Lack of adequate data management may lead to low quality clinical research. Thus, it is of great importance to establish a set of standards for data management so as to improve the quality of clinical research. Based on the real practice in Myocardial Infarction Secondary Prevention Study in TCM (MISPS-TCM), this article introduces methods on data audit in clinical trials of TCM.
Clinical practice guidelines need to be based on evidence, but traditional Chinese medicine, especially integration of traditional Chinese and Western medicine guidelines, inevitably need to combine clinical research evidence, ancient literature, and expert experience and consensus. In the process of formulating, there are deviations in understanding and application of the expert consensus method and expert experience, resulting in opaque of the recommendations, unclear of the details of the diagnosis and treatment strategy, less prominent of the advantages and value of traditional Chinese medicine, which affects the scientificity, transparency, applicability, promotion and application of the guidelines of traditional Chinese medicine or integration of traditional Chinese and Western medicine. This study discusses the guiding principle of "evidence as a core, consensus as a supplement, and experience as a reference" that was generally followed and puts forward detailed methodological suggestions to the formulation of guidelines for traditional Chinese medicine and integration of traditional Chinese and Western medicine.
Objective While reporting of adverse drug reactions (ADR) and adverse drug events (AE) following Chinese medicine injection (CMI) is becoming more common, the reporting quality is of concern. Methods A checklist about the reporting quality of ADR/AE was set up, and the ADR/AE reporting of Herba Houttuyniae injection was chosen as an example. Electronic databases Chinese Journal Net (CJN) (1994-2009) and Chinese Science and Technological Journal Net (VIP) (1989-2009) were searched for target literature. Results Based on our search strategy, 210 articles were included, with 175 articles reporting single or several cases of ADR/AE following Herba Houttuyniae injection (type I report). There were 7 reports from regional or national ADR monitoring centers (type II report), and 28 summary reports from a single hospital or medical center (type III report). All 210 papers mentioned ‘adverse effect,’ ‘safety’ or related meaning words in their titles, but 199 articles did not have abstract. Patient demographic characteristics were not fully reported in these articles. In type I articles, only 97 cases (43.11%) mentioned whether patients had or did not have a history of allergies, while 128 cases (56.89%) in Type II papers and Fourteen (50%) type III papers, did not mention allergic history of patients. Only three articles (3/210, 1.43%), all of them type I, mentioned the syndrome type in Chinese medicine. None of the papers gave clear indications of the type and grade of ADR/AE of patients. Most papers did not report details of the CMI procedure, such as the drug company, product serial number, or the drug’s validity period. Data about the occurrence time and management of ADR/AE was also inadequately reported. Conclusion and recommendations The current reporting format of ADR/AE in clinical CMIs is not standardized. Much fundamental information of ADR/AE following CMI is therefore missing. A standard reporting format for ADR should be developed, and should include the following: 1) a title mentioning adverse effects and safety; 2) a structured abstract including adequate information about the patient and the disease treated, the drug used, the specific ADR/AE, physician response to the ADR/AE, and result of management; 3) demographic characteristic of the patients (gender, age, etc.); 4) clinical characteristics of patients (disease, syndrome, etc); 5) allergic history of patients; 6) diagnosis and syndrome based on Chinese medicine theory; 7) detailed information about the Chinese materia medica intervention (the manufacturer of the drug, series number, valid dates, dosage, route of administration, menstruum, dripping speed, etc.); 8) concomitant drug use; 9) time and symptoms of ADR/AE; 10) type and grading of ADR/AE; 11) physiological systems affected by ADR/AE; 12) specific treatment and prognosis for ADR/AE; 13) evidence of the cause and effect of ADR/AE; 14) any other possibility of ADR/AE. Also, a ADR/AE registration system should be established.