Assessment on adverse drug reactions (ADR) that directly affects the quality of life and mortality and an important part of the post-marketed reassessment are developing gradually in China. Many problems have been identified in clinical validity and safety for the authorized Chinese herbs. An effective and standardized system is needed in the post-marketed drug reassessment. Evidence-based drug evaluation, which mainly includes clinical epidemiology, systematic review and health technology, will be used to assess the clinical validity, safety and cost of post-marketed drug and play an important role in the process of modernization and internationalization of Chinese herbs.
In the clinical trials, the rights and interests of participants must be considered. Ethical principles including the Declaration of Helsinki for clinical research have been established, and the institutional review board (IRB) and informed consent are important for protecting the rights and interests of participants. Whether a clinical trial is in accordence with the ethics depends on if the available clinical evidence is valuable and credible. The better candomize controlled trial (RCT) is one of the best evidence which will make different results equal between the treatment group and the controlled group. Thus benefits and risks of participants are allocated equitably and useless treatment is prohibited when the effective treatment affirmed at the same time. Economic health evaluation and outcome measurements are emphasized in EBM, and the clinical evidence is updated regularly. It is EBM and its emphasis of evidence that need the high-quality clinical trials, therefore the problems of ethics involved in clinical trials is important.
Objective To investigate the status of clinical practices and side effects related to Shenfu injection.Method We searched the China National Knowledge Infrastructure (CNKI) database using the key word “Shenfuinjection”. Original clinical studies of Shenfu injection which were published from January 1993 to December 2008 inChinese magazines were included. Results A total of 576 relevant clinical studies were identified. There were 21 496 cases in the study group and excluding the control group patients. We investigated and analyzed the side effects of Shenfu injection. For cases with side effects, the medication dosage, the diseases for treatment, the method of medication, the menstruum, and course of treatment for the side effects were evaluated. All the side effects were mild except one case of anaphylactic shock. Conclusion Shenfu injection has been widely used in clinical patients since it came into the market in 1993. However, systematic evaluation of its clinical application is lacking, and there are some unsolved problems and deficiency in selecting and expanding diseases for treatment, evaluating the dosage and treatment method, and investigating the side effects of the drug. Therefore, it is imperative to enhance the evaluation drugs and good clinical application after the drugs come into the market with evidence-based medicine.
Objective To assess the quality of the published randomized controlled trials published in Journal of Beijing University of Traditional Chinese Medicine (JBUTCM), Acta Universitatis Traditionis Medicalis Sinensis Pharmacologiaeque Shanghai (AUTMSPS), Journal of Guangdong University of Traditional Chinese Medicine (JGUTCM), and Journal of Chengdu University of Traditional Chinese Medicine (JCUTCM) from 2000 to 2005. Method Guided by the Cochrane Center hand-searching guidelines, we searched 24 volumes (111 issues) of the four journals. The data were extracted according to the principles of clinical epidemiology and consolidated standards of reporting trials (CONSORT), as well as an evaluation scale for randomized controlled trials (RCTs). The data were managed by descriptive analysis and uniformity test. Results There were 365 RCTs. The diagnostic criteria were reported in 297 trials (81.37%). The inclusion and exclusion criteria were reported in 143 trials (39.18%) and 132 trials (36.16%), perspectively, None mentioned the estimation of sample size. The randomization and allocation concealment were reported in 70 trials (19.18%) and 9 trials, perspectively. The baseline data were described in 292 trials (80.00%). Blinding was mentioned in 35 trials (9.59%).Withdrawal occurred in 20 trials (5.48%). Informed consent was acquired in 2 trials. Adverse drug reactions were described in 97 trails (26.58%). Conclusion There are deficiencies in the reporting of these RCTs, Most of the trials do not describe the randomization, only a few trials use the allocation concealment and blinded method, no description of comparability of baseline data, most of the trials do not report the inclusion and exclusion criteria, and none estimate the sample size. These problems indicate that it is necessary to improve the quality of clinical research in Chinese medicine and pharmacology.
Medical ethics must be considered for protecting the fights and interests of patients in clinical trials. Now the fights of the subjects are more and more emphasised, but there are some problems. It is evidence-based medicine (EBM) and emphasis of evidence that need the high-quality clinical trials, yet it violates the principle of ethics in some degree. It will be helpful for the administrators to supervise the clinical trials on drugs well from the point of ethical views.
Objective To assess the quality of randomized controlled trials (RCTs) and clinical controlled trials (CCTs) relevant to COPD besides chronic bronchitis and chronic pulmonary cor disease in strengthening immune published in Chinese medical journals to provide scientific basis of systematic review (SR) of regulating the immune function of COPD in Chinese herbs. Methods 54 articles with clinical controlled trials were obtained by electronic searching and handsearching, and the method for randomized allocation, blindness, multi-centres, sample sizes, diagnosis criteria, exclusion criteria, source of cases, immune markers (cellular immunity, humoral immunity, erythrocyte immunity, nonspecific immunity), the clinical outcome assessment, statistical management, course of treatment and the side effects or adverse drag reaction, follow-up were investigated and then methodologically evaluated. According to the investigation, literatures with the method for randomized allocation, correct controls, appropriate sample sizes (≥60), the nation-wide diagnosis criteria, the objective clinical outcome assessment distinct statistical method were stipulated as the high-quality ones relatively. Results Among the 54 trials, 70.4% had explicit diagnosis criteria, 18.5% with exclusion criteria, 20.4% with comparability of baseline, 37.0% with distinct statistical method. In the therapy, 63.0% were with Chinese herbs. Conclusion The selected 7 articles belong to the high quality and possibly are to be explored in Meta-analysis.
Objective To evaluate the effectiveness and safety of Lianpu granule (LPG) in the treatment of common cold (Feng-Re syndrome). Methods The clinical trials were conducted by good clinical practice (GCP). In the phaseⅡ, a double-blind controlled trial involving 48 patients with common cold (Feng-Re syndrome) allocated by a random number table to receive LPG (n=24) or compound oral liquid of Shuanghuanglian (SHL) (n=24) as conducted; the other 80 patients included in the phase Ⅲ, multi-center randomized and controlled trial were divided into the LPG group (n=60) and SHL group (n=20) by a random number table. We didn’t evaluate the allocation concealment. LPG was administered as a dose of 8 g, three times a day, and SHL, as a dose of 10 ml, three times a day. The treatment duration for both groups was 3 days. All data were analyzed by using stata 7.0 for per-protocol population. Results In the Lianpu granule group, the good improvement rates were 90.00% (18/20) and 85.00% (51/60), and the improvement rates were 95.00% (19/20) and 98.33% (59/60); the good improvement rates for traditional Chinese medicine syndromes were 85.00% (17/20) and 85.00% (51/60), and the improvement rates were 95.00% (19/20) and 98.33% (59/60); the good improvement rates for fever were 85.00% (17/20) and 86.05% (37/43), and the improvement rates were 95.00% (19/20) and 95.35% (41/43) in the phase Ⅱ and Ⅲ respectively. Meanwhile for the compound oral liquid of SHL group, the good improvement rates were 85.71% (18/21) and 80.00% (16/20), and the improvement rates were 95.24% (20/21) and 95.00% (19/20); the good improvement rates for traditional Chinese medicine syndromes were 85.71% (18/21) and 80.00% (16/20), and the improvement rates were 95.24% (20/21) and 95.00% (19/20); the good improvement rates for fever were 85.71% (18/21) and 80.00% (12/15), and the improvement rates were 90.48% (19/21) and 93.33% (14/15) in the phase Ⅱ and Ⅲ respectively. No significant differences were seen between LPG and SHL groups on treatment duration, clinical effect and improvement rate for fever (all P ＞0.05). No adverse effects were seen in this study. Conclusion LPG has showed a definite clinical effect on common cold (Feng-Re syndrome) with no observed adverse effects.
Objective To evaluate the efficacy and safety of Tongxiening granule （TXNG） in the treatment of diarrhea-predominant irritable bowel syndrome （IBS） （stagnation of the liver-qi attacking the spleen）. Methods In a prospective, randomized, placebo-controlled, double-blind clinical trial, 60 patients with diarrhea-predominant IBS were randomly divided into the TXNG group （TXNG, 5.0g, 3 times daily; n =30） and the placebo group （placebo, 5. 0g, 3 times daily; n =30）. The treatment was administered for 3 weeks, and the follow-up was conducted for 4 weeks.Results （1）Abdominal pain： The cure rates were 57. 7% vs. 16. 0% （ by per-protocol analysis, PP） and 31.0% vs. 7.1% （ by intention-to-treat analysis （ITT） ; and the overall improvement rates were 92.3% vs. 44.0% （PP） and 82.7% vs. 39.3% （ITT） in the TXNG and the placebo groups respectively （ P 〈0. 05）. （2） Diarrhea ： the cure rates were 46. 2% vs. 20. 0% （PP） and 41.4% vs. 17. 9% （ITT） , and the overall improvement rates were 96. 2% vs 48. 0% （PP） and 86. 2% vs 42.9% （ITT） in the two groups respectively （P 〈0.05）. （3）Traditional Chinese medicine symptoms： the cure rates were 30.8% vs. 4.0% （PP） and 27.6% vs. 3.6% （ITT） ; and the overall improevment rates were 92.3% vs. 48.0% （PP） and 82.7% vs 42.9% （ITT） in the two groups respectively （P 〈0. 05）. The pain duration after treatment in the TXNG group was significantly shortened compared with the placebo group （7.6 ±4. 6d vs 14. 4 ±4. 3d, P =0. 0125）. After 4-week follow-up, it suggested that the recrudescent duration in symptoms related to IBS in the TXNG group was longer than that in the placebo group （11.5 ±5.3 d vs 6.2 ±6.9 d, P = 0. 019）. No adverse effects were found in the TXNG group. Conclusion It was demonstrated that TXNG is effective and safe in the treatment of diarrhea-predominant ms （stagnation of the liver-qi attacking the spleen）.
Objective To analyze the clinical application, ADR/AE involved systems and manifestations of the six injections containing Houttuynia cordata which are much complicated in their ingredients and pharmacological actions compared with the Houttuynia cordata Injection, and to assess their safety and efficacy, so as to provide references for further deep research. Methods Such databases as MEDLINE (1998 to December 31, 2010), EMBASE (1998 to December 31, 2010), The Cochrane Library (1998 to December 31, 2010), CNKI (1979 to December 31, 2010), CBM (1978 to December 31, 2010), and VIP (1989 to December 31, 2010) were searched to retrieve the case report, series of cases observation, cross-sectional study, and clinical control study. The studies were included according to the inclusive and exclusive criteria, and the data was abstracted to analyze the reason and regularity of ADR/AE. Meta-analyses for efficacy were conducted when the data was feasible. Results a) About ADR/AE: Among the included 132 studies, 118 cases were reported with the ADR/AE. There were 59 studies about the New Houttuyfonate sodium injection, 93 cases with ADR/AE mainly manifested as pain in injection site (41 cases), rash (19 cases), anaphylactic shock (11 cases) and other infusion or allergic reactions (21 cases). There were 69 studies about the Yu Jin injection, 25 cases with ADR/AE manifested as rash (12 cases), anaphylactic shock (four cases), pain in injection site (three cases), and other infusion or allergic reactions (six cases); and b) The good efficacy of the New Houttuyfonate sodium injection and the Yu Jin injection was reported in one cross-sectional study and one RCT respectively, but the limited data was not enough to properly judge the efficacy. Conclusion There are few of clinical studies about these six injections containing Houttuynia cordata, and the irrational use in clinic is serious. Most of the ADR/AE cases are related to irrational use, such as, non-indication use, and arbitrarily change of administration method. The proof for analyzing and evaluating the safety and efficacy of injections containing Houtturnia cordata is insufficient, so strict clinical trials with large sample size are required to support further research.
【摘要】 目的 评价九味柔肝颗粒治疗慢性乙肝肝纤维化的疗效和安全性。 方法 根据纳入与排除标准，选取2007年2-8月入院的慢性乙肝肝纤维化（气滞血瘀兼湿热未净证）患者96例，按3∶1随机分为两组进行随机双盲双模拟对照试验。试验组72例，口服九味柔肝颗粒， 2次/d，每次10 g；阳性对照药鳖甲软肝片组（对照组）24例，口服鳖甲软肝片，4片/次，3次/d；两组疗程均为6个月。 结果 试验组完成治疗66例，对照组完成21例。符合方案数据分析（PPS）结果显示，试验组治疗后中医证侯积分及B超积分分别下降了0.50±1.04和8.61±3.62，对照组分别下降了0.32±1.01和8.63±3.15，均较治疗前显著下降（Plt;0.05），两组比较无统计学意义（Pgt;0.05）。在血清肝纤维化四项指标方面，试验组除LN外，其余指标治疗后均较治疗前明显下降（Plt;0.05），对照组中仅PⅢP有显著下降（Plt;0.05），其余指标下降不明显，两组比较无统计学意义（Pgt;0.05）。两组患者治疗期间均未观察到明显不良反应，不良反应发生率分别为5.56%和4.17%。 结论 九味柔肝颗粒能明显改善慢性肝炎肝纤维化患者的症状和部分肝纤维化指标，其疗效与鳖甲软肝片相当，安全性良好。【Abstract】 Objective To assess the safety and therapeutic effect of Jiuweirougan grandule on chronic hepatitis B with hepatic fibrosis. Methods A double-blind, double dummy and randomized controlled method was adopted. Ninety-six patients from February to August 2007 selected by including and excluding criteria were distributed randomly in accordance with the 3∶1 ratio into the test group (n=72, treated with Jiuweirougan 10 g, two times per day) and the control group (n=24, treated with Biejiaruangan 4 tablets, three times per day). The period of treatment for both groups lasted for half a year. Results A total of 66 cases in the test group and 21 cases in the control group completed the experiment. The results of per-protocol population (PPS) suggested that the accumulated score of B ultrasound and symptom decreased 0.50±1.04 and 8.61±3.62 in the test group and 0.32±1.01 and 8.63±3.15 in the control group, respectively. The score decreased remarkably compared with pre-treatment(Plt;0.05). There was no significant difference between the two groups (Pgt;0.05). For serum liver fibrotic parameters, all parameters except laminin (LN) in the test group decreased remarkably compared with pre-treatment(Plt;0.05). But in the control group, besides type Ⅲ procollagen (PCⅢ) decreased remarkably(Plt;0.05), other parameters showed no obvious changes. There was no significant difference between the two groups (Pgt;0.05). At the same time, no obvious adverse effect was found in the two groups. The incidence of adverse reactions was 5.56% and 4.17% respectively. Conclusion Jiuweirougan granule may improve the syndrome and part of fibrotic index of chronic hepatitis B with fibrosis, and the effect is equal to that of Biejiaruangan with good security.