Objective To assess the efficacy and safety of Chinese medicinal herbs for asymptomatic hepatitis B virus(HBV) infection. Data Source The trials registers of the Cochrane Hepato-Biliary Group, the Cochrane Library and the Cochrane Complementary Medicine Field were searched in combination with MEDLINE, EMBASE, and handsearches of Chinese journals and conference proceedings. Data Selection Randomized clinical trials with 3 months follow-up comparing Chinese medicinal herbs versus placebo, no intervention, non-specific treatment, or interferon treatment for asymptomatic HBV carriers were included. No language and blinding limitations were applied. Data Extraction Data were extracted independently by two reviewers. The methodological quality of trials was assessed by the Jadad-scale plus allocation concealment. Results Three randomized clinical trials (307 patients) with low methodological quality following patients for three months or more after the end of treatment were included. Herbal compound Jianpi Wenshen recipe showed significant effects on clearance of HBV markers compared to interferon: relative risk 2.40 (95 % CI 1.01 to 5.72) for clearance of serum HBsAg, and 2.54 (1.13 to 5.70) for seroconversion of HBeAg to anti-HBe. Phyllanthus amarus and Astragalus membranaceus showed no significant antiviral effect compared with placebo. Analysis of pooling eight randomized clinical trials with less than three months follow-up did not show a significant benefit of Chinese medicinal herbs on viral markers. No serious adverse event was observed. Conclusions There is insufficient evidence for treatment of asymptomatic HBVcarriers using Chinese medicinal herbs due to the low quality of the trials. Further randomized, double blind, placebo-controlled trials are needed.
Objective To learn the current situation of traditional Chinese medicine (TCM) systematic reviews/meta-analyses published in Chinese journals. Methods All TCM systematic reviews/meta-analyses published from 1978 to July 31, 2009 were searched in the Chinese Biomedical Database (CBM). According to the inclusion and exclusion criteria, relevant information was extracted on the basis of research purpose. Meanwhile, publication year, journal name, author’s district, number of authors and their articles, types of diseases and interventions were took as the indexes, and then descriptive analysis was performed using SPSS 15.0 software. Results A total of 245 articles including 238 in Chinese and 7 in English were included. All of them were published in 117 different journals from 1998 to 2008, showing an accelerating growth trend of article number. In addition to only one article with first author from Germany, the first author of other 244 were from 24 domestic provinces (autonomous regions and municipalities); the number of authors ranged from 1 to 11; a total of 186 people had published articles as first author, and the number of their published articles ranged from 1 to 29. There were 16 types of diseases according to the International Classification of Diseases 10th Edition (ICD-10). Totally, 218 articles took drugs as interventions (including 106 listed drugs, 25 self-made prescriptions, 70 related to both listed drugs and self-made prescriptions, and 17 without reporting detailed interventions), accounting for 89%; and 27 articles were about non-drug interventions (including 26 about acupuncture and 1 about massage), accounting for 11%. Most (95.8%) of the articles about self-made prescriptions and listed drugs/self-made prescriptions adopted inappropriate pooled analyses. Conclusion Evidence-based medicine has been spread into the field of TCM, the number of TCM systematic reviews/meta-analyses shows an accelerated growth trend. The types of diseases discussed in the literature were almost the same as the diseases those could be effectively treated by TCM, but there existed imbalance in districts. In the future, systematic review/meta-analysis on drug intervention should aim at Chinese patent medicines and single medicines rather than self-made prescriptions, and should pay more attention to advantageous drugs and advantageous treatments of diseases. Moreover, importance should be also attached to clinical heterogeneity controlling when using acupuncture as a non-drug intervention.
Objectives To discuss the methodology of evaluation of traditional Chinese medicine (TCM) placebo simulation effects and the problems of blind implementation and so as to improve the quality of double-blind clinical trials of TCM. Methods Focusing on case of placebo preparation of TCM investigational new drug, simulation effects of the placebo were evaluated in terms of shape, color, taste and smell. The possibility of placebo be a drug and the similarity between placebo and drug were tested. Results There was no significant difference between placebo and investigational new drug to be judged as a drug (P>0.05). As for the similarity between placebo and drug, there was no significantly difference of the shape (P>0.05), for which the similarity was 100%. The color, taste and smell were significant different between placebo and drug (P<0.05), for which the similarity were 50%, 10% and 15% respectively. Conclusions It is very difficult to simulate TCM based on its certain color, taste or smell. Therefore, the subjects and the investigators’ compliance should be kept to avoid breaking the blind intentionally in the process of the trial and the influence of unblinding should be estimated at the end of the trial.
Objective To assess the quality of published systematic reviews and meta-analyses on Traditional Chinese Medicine (TCM) published in Chinese journals. Methods We searched CNKI, CMB from January 1995 to December 2006 and The Cochrane Library (Issue 4, 2006) for systematic reviews and meta-analyses on TCM. We extracted details of the interventions used in the treatment and control groups, analyzed the validity of included studies and investigated whether the reports used QUOROM statement or not. Results We identified 111 reports, of which 1 on prevention, 1 on adverse events, 1 on risk factors and premonitory symptoms, 2 on physiochemical parameters, and 106 on effectiveness and safety assessment. In total, 42 types of diseases were involved, and 41 reports were related to cerebrovascular diseases. As for the investigated interventions, 25 studies assessed TCM and 12 assessed acupuncture. Two had no control intervention design control in the group, 15 did not describe the interventions in the control group, 50 used active control (26 for western medicine, 12 for Chinese medicine, 12 for western plus Chinese medicine), 14 used blank control, 17 used baseline control, 4 used sham acupuncture or acupoint injection control etc., 5 used placebo control and 4 used "mutual control". The interventions used in the treatment and control groups varied widely. The number of trials included in the reviews and meta-analyses ranged from 1 to 35, and 24 studies included non-randomized controlled trials. Of the 111 reports, 14 were Cochrane reviews, 16 did not assess the quality of included randomized trials and a further 22 performed only simple and nonstandard quality assessment of the included trials. None of the reviews or meta-analyses used the QUOROM statement to report their results. Conclusions Because of the unique characteristics of TCM, systematic reviews of TCM should focus on a specific topic, avoid the selection of too many drugs, address the target indications of the test drugs and pay attention on intervention evaluation. High quality systematic reviews of TCM are needed but they will only be produced through the concerted efforts of clinicians, TCM practitioners and methodologists.
This article introduces a dynamical stratified blocked randomized algorithm when the static stratified blocked randomized algorithm is not suitable to resolve the problem caused by uncertain stratified factors and levels during calculation of the sample size at the stage of clinical trial design. Prior to the start of the clinical trial, a list of random numbers is created by blocked randomized algorithm. During field implementation, a block of random numbers is dynamically allocated to a stratify level. Thereafter, a subject is randomized into different groups in that block. The study of Chinese medicine for gastric cancer anemia and blood hypercoagulability is used as an example to illustrate how to design and implement dynamic stratified block randomized algorithm. The results show that the dynamic stratified block randomized algorithm is more flexible and adaptable than the static stratified blocked randomized algorithm. However, its application is more complex and requires higher standards in clinical trials.
Master protocol is a great transformation of clinical trials with complete research network, reasonable design and innovative statistical analysis methods. It is a highly efficient new model of clinical trials which could obtain more medical information with less clinical resources. Clinical researches in the field of oncology using master protocol have already made delightful achievements. This paper introduces the design of clinical trials on angina pectoris of coronary heart disease, myocardial infarction and heart failure for instance and discusses the application of master protocol to clinical researches of Traditional Chinese Medicine combined with the differentiation of syndromes and treatments. We expect to provide new ideas and methods for the design of master protocol on diseases with similary syndrome pattern series of Traditional Chinese Medicine.
Objective To assess the efficacy and safety of Chinese herbal medicines for chronic functional constipation. Methods We searched CNKI (1989 to November, 2009), CBM (1989 to November, 2009), VIP (1989 to November, 2009), Cochrane Library (Issue 4, 2009), PubMed (1966 to November, 2009) and EMbase (1986 to November, 2009). All randomized and quasi-randomized clinical trials of treating chronic functional constipation with Chinese herbal medicines versus untreated, placebo or western drug groups were included. Data were extracted independently by two reviewers. The methodological quality of trials was evaluated with Cochrane Handbook 5.0.2 criteria. Meta-analyses were conducted by the RevMan 5.0 software. Results Twenty-one trials involving 2 602 patients were included. The Meta-analysis results showed that: Chinese herbal medicines improved both syndromes and colonic transit function of recipients; moreover, it is superior to both gastrointestinal prokinetic agent in effective rate (RR=1.18, 95%CI 1.12 to 1.25), healing rate (RR=1.59, 95%CI 1.35 to 1.88), and cathartic in effective rate (RR=1.18, 95%CI 1.10 to 1.27), healing rate (RR=1.16, 95%CI 1.29 to 2.10). Integration of Chinese herbal medicines and gastrointestinal prokinetic agent is superior to gastrointestinal prokinetic agent in effective rate (RR=1.21 95%CI 1.09 to 1.34) and healing rate (RR=1.41, 95%CI 1.11 to 1.79). Conclusion Some Chinese herbal medicines may be effective and safe in treating chronic functional constipation, which can not be bly proved at present for lack of studies with high quality.
Intensive discussions and debates concerning whether we should and how to apply evidence-based medicine (EBM) research in traditional Chinese medicine (TCM) have arisen worldwide. We always hold the opinion: TCM needs EBM; the evidence from EBM is not limited to randomized controlled trials and systematic reviews; innovative methodological studies are urged based on the characteristics of TCM theoretically and clinically. Based on the methodological training and studies in this area, the authors discussed how to promote the evidence based TCM from five aspects including completing clinical trial procedure, reporting clinical trials according to international standards, reviewing the current clinical studies on TCM systematically, promoting the methodological research and academic exchange and better evidence (knowledge) management.
Traditional Chinese Medicine (TCM) standardization is an important carrier for TCM inheriting and innovating. As an important content of TCM standardization system, TCM clinical practice guidelines' designation and revision play an important role for medical staff to regulate medical behavior, and improve the quality of health services. This paper expounds the significance and function of the TCM guidelines, analyzes the present situation, opportunities and challenges, and puts forward the strategies and suggestions to promote the development of evidence-based TCM guidelines.