112 Side Of The "treatise On The Modern Clinical Research Evidence-based Medicine Evaluation

BackgroundThe Treatise on Febrile Diseases (Shang Han Lun), as the essence of Traditional Chinese Medicine (TCM) theory, has guided TCM clinical practice for thousands of years. The formulas recorded in the Treatise have stringent configurations of medicinal substances, with clear treatment objectives, and high specificity and practicality. Even today, many formulas are still widely used in clinical practice and are respected for their prompt curative effects. With the current emphasis on evidence-based medicine, TCM is facing the challenge of providing evidence of the therapeutic effectiveness of formulas in the Treatise. In this study, we systematically collected, analyzed, and appraised the clinical literature on the formulas, using methods of evidence-based medicine, with the aim of paving the way toward the development of"evidence-based TCM."Objectives1. Biblio-metrics methodology was used to describe the status quo and distribution in the literature from the past 30 years of 112 formulas recorded in the Treatise on FebrileDiseases.2. Ten formulas were selected and their related disease systems and categories in modern clinical practice were explored; their therapeutic effectiveness was preliminarily appraised to provide evidence for further clinical practice and scientific research.3. The therapeutic effectiveness and safety of Xiao Chai Hu Tang as well as Xiao Qing Long Tang were assessed by systematic review to provide evidence for clinical practice. In sum, the aim of this study is to provide evidence for further research on formulas in the Treatise on Febrile Diseases to guide TCM clinical practice and to improve treatment using these formulas from the perspective of modern evidence-based medicine.Methods1. Biblio-metrics on literature from the past 30 years on 112 formulas contained in the Treatise on Febrile Diseases .Literature from 1979 to 2006 on 112 formulas contained in the Treatise on Febrile Diseases were obtained from a computerized search of the Chinese National Knowledge Infrastructure (CNKI) database. Biblio-metrics was used to analyze the total number of articles published, the number of articles published annually, and the annual proportion of articles published. The results were then organized hierarchically in tabular form, listing the top 10 formulas.2. Selection and analysis of disease systems and categories for the top 10 formulas. Based on the results of the aforementioned biblio-metrics and on the International Classification of Diseases (ICD-10), the disease systems and categories related to the top 10 formulas in the hierarchical list were analyzed, to find out the field and disease in which these formulas have advantages in modern clinical practice.3. Systematic review of the therapeutic effectiveness of selected formulas. Based on the results of the above biblio-metrics, the formulas Xiao Chai Hu Tang and Xiao Qing Long Tang, which occupied the first and tenth place in the hierchical list, respectively, and were both being intensively researched in China and abroad, were selected. Conforming to the principle of systematic review in evidence-based medicine, we first enrolled relevant studies, then performed critical appraisal and data analysis of the included studies. Finally evidence on the treatment and safety of the two formulas was ascertained to provide evidence for TCM clinical practice and future scientific research.Results1. Biblio-metrics of 112 formulas in the Treatise on Febrile Diseases in the past 30 years.1.1 From 1979 to 2006, a total of 38,472 studies on the 112 formulas were obtained from CNKI database. These studies were unevenly distributed. Nearly 50% of the total literature was comprised of the top 10 formulas in the hierarchical list, while no studies involved the last 12 formulas.1.2 The top 10 formulas in the hierarchical list of 112 formulas in the Treatise on Febrile Diseases were in sequence as follows: Xiao Chai Hu Tang, Gui Zhi Tang, Da Cheng Qi Tang, Ban Xia Xie Xin Tang, Si Ni San, Shao Yao Gan Cao Tang, Dang Gui Si Ni Tang, Ma Huang Xing Ren Gan Cao Shi Gao Tang, Wu Ling San, and Xiao Qing Long Tang.2. Identification and analysis of the disease systems and categories of the top 10 formulas in the hierarchical list (see table0-1).3. Systematic review of randomized control trials (RCTs) on the therapeutic effectiveness of formulas in the Treatise on Febrile Diseases.3.1 Safety of formulas in the Treatise on Febrile Diseases.3.1.1 A total of 38 RCTs were included with 4,327 subjects, including chronic hepatitis B (CHB) patients, hepatocirrhosis patients, and alcoholic liver disease(ADL) patients. According to the international standard appraisal criteria, most of these studies were of low quality, mainly reflected by inadequate/incorrect reporting of methodology.3.1.2 The results of systematic review demonstrated that:(1) Xiao Chai Hu Tang combined with other antiviral therapy showed better therapeutic effect than antiviral therapy alone in improving liver function of chronic hepatic disease patients: decreasing ALT(relative benefit 95%CI: WMD-22.86 [-38. 38,-7.35];P=0.004), AST(relative benefit 95%CI: WMD-22.97[-42.88,-3.07];P=0.02), and TB (relative benefit 95%CI: WMD-4.11[-7.79,-0.42];P=0.03).(2) The result of antivirus effect showed that: Xiao Chai Hu Tang combined with antivirus treatment had better therapeutic effect than antivirus treatment or symptomatic treatment alone; Xiao Chai Hu Tang showed obviously better therapeutic effect in eliminating HBV-DNA than symptomatic treatment; compared with autologous LAK cell infusion treatment alone, Xiao Chai Hu Tang combined with autologous LAK cell infusion showed better therapeutic effect in eliminating HBV-DNA ( relative benefit 95 % CI :RR1.36[1.01,1.82],P=0.04).(3) Xiao Chai Hu Tang combined withγinterferon showed better therapeutic effectiveness in decreasing sero fibrosis index (PIIIP, LN,HA) thanγinterferon alone(PIIIP: relative benefit 95%CI:WMD44.28[20.49,68.07],P=0.0003;LN:relative benefit 95%CI:WMD35.73[23.81,47.66] , P<0.00001 ; HA : relative benefit 95 % CI :WMD78.31[49.48,107.13],P<0.00001).3.1.3 Xiao Chai Hu Tang can relieve the side effects, such as flu-like symptoms and low fever, induced by antiviral treatment or autologous LAK cell infusion.3.1.4 No serious adverse effect of Xiao Chai Hu Tang was reported in all the studies that reported the adverse effects. 3.2 Systematic review of RCTs on Xiao Qing Long Tang in treating asthma.3.2.1 A total of 26 RCTs, involving 2,028 asthma patients, were included. Similar to that of systematic review of Xiao Chai Hu Tang, the general quality of the included RCTs was relatively poor; no RCTs of high quality were identified.3.2.2 Meta-analysis results show that Xiao Qing Long Tang combined with western medicine had better therapeutic effect in controlling asthma symptoms than western medicine alone (RR1.50;95%CI 1.27 to 1.76, P<0.00001); the therapeutic effect of Xiao Qing Long Tang alone in relieving symptoms was about the same as with western medicine alone (RR1.24;95%CI 0.92 to 1.66, P>0.05). As for respiratory function improvement, our study demonstrated that Xiao Qing Long Tang combined with western treatment had significant therapeutic effect: FEV1(L):(WMD-0.84;95%CI -1.03 to -0.65, P<0.00001; WMD-0.66; 95%CI -0.76 to -0.55, P<0.00001);PEF(L/S)WMD-1.56;95%CI -1.72 to -1.40, P<0.00001; WMD-1.57; 95%CI -2.08 to -1.06, P<0.00001). Finally, Xiao Qing Long Tang also showed effect in reducing serum eosinophil (EOS) and IgE levels, with the possible mechanism being through controlling airway inflammation and hyper-reactivity of asthma patients.3.2.3 In the four studies that reported adverse effects with Xiao Qing Long Tang, no serious side effects were found.Conclusions1. The literature on the 112 formulas in the Treatise on Febrile Diseases during the recent 30 years was unevenly distributed. The top 10 formulas in our hierarchical list of the 112 formulas that were most intensively studied included Xiao Chai Hu Tang, Gui Zhi Tang, Da Cheng Qi Tang, Ban Xia Xie Xin Tang, Si Ni San, Shao Yao Gan Cao Tang, Dang Gui Si Ni Tang, Ma Huang Xing Ren Gan Cao Shi Gao Tang, Wu Ling San, and Xiao Qing Long Tang.2. Identification and analysis of the disease systems and categories of the top 10 formulas found that modern clinical use of the formulas basically conformed to the pathogeneses described in the Treatise on Febrile Diseases. We also found that there were some modern practitioners who were innovative in their use of the formulas, broadening the disease scope of the formulas by conforming to the pathogeneses described in the Treatise.3. The use of Xiao Chai Hu Tang in the treatment of chronic liver disease and of Xiao Qing Long Tang in the treatment of asthma were both supported by RCTs with no serious adverse effects reported. However, due to the low quality of the studies that were included, the therapeutic effects might have been exaggerated and therefore have limited the general applicability of the conclusions. More rigorously designed multi-center, large-sample, randomized, double-blinded, placebo trials on the therapeutic effectiveness and safety of the formulas on specific diseases are warranted.