Problems and thoughts in clinical safety evaluation of traditional Chinese medicine / 中国中药杂志

Amid the modernization and internationalization of traditional Chinese medicine(TCM), the safety of TCM has attracted much attention. At the moment, the government, scientific research teams, and pharmaceutical enterprises have made great efforts to explore methods and techniques for clinical safety evaluation of TCM. Although considerable achievements have been made, there are still many problems, such as the non-standard terms of adverse reactions of TCM, unclear evaluation indicators, unreasonable judgment methods, lack of evaluation models, out-of-date evaluation standards, and unsound reporting systems. Therefore, it is urgent to further deepen the research mode and method of clinical safety evaluation of TCM. Based on the current national requirements for the life-cycle management of drugs, this study focused on the problems in the five dimensions of clinical safety evaluation of TCM, including normative terms, evaluation modes, judgment methods, evaluation standards, and reporting systems, and proposed suggestions on the development of a life-cycle clinical safety evaluation method that conformed to the characteristics of TCM, hoping to provide a reference for future research.

Evaluation methods of clinical efficacy of traditional Chinese medicine / 中国中药杂志

Clinical efficacy is the basis for the development of traditional Chinese medicine(TCM), and the evaluation of clinical efficacy of TCM has always been the focus of attention. The technical and methodological difficulties in the evaluation process often restrict the generation of high-level evidence. Therefore, methodological research should be deepened and innovative practice should be carried out to study the application of scientific research methods in the evaluation of the advantages of TCM. After more than ten years of development, the clinical efficacy evaluation of TCM, on the basis of the initially classic placebo randomized controlled trials, has successively carried out a series of meaningful attempts and explorations in N-of-1 trials, cohort studies, case-control studies, cross-sectional studies, real world studies, narrative medicine studies, systematic evaluation, and other aspects, laying the foundation for the transformation of TCM from "experience" to "evidence". This paper focused on the clinical efficacy evaluation of TCM, summarized the main connotation and development status of efficacy evaluation indicators, standards, and methods, and put forward corresponding countermeasures and suggestions for the problems of indicator selection, standard formulation, and methodology optimization in the research process. It is clear that scientific and objective evaluation of the efficacy of TCM is an urgent problem to be solved at present.

Systematic review of efficacy and safety of Compound Danshen Injection combined with Western medicine in treatment of vascular dementia / 中国中药杂志

To evaluate the efficacy and safety of Compound Danshen Injection combined with Western medicine in the treatment of vascular dementia. Databases of Cochrane Library, PubMed, EMbase, CNKI, SinoMed, VIP, Wanfang Data were electronically retrieved for collecting randomized controlled trial(RCT)about vascular dementia treated with Western medicine alone or combined with Compound Danshen Injection from the year of database establishment to January 2020. Two researchers independently screened out li-teratures, extracted data, and evaluated the risk of bias for inclusion in the study. Meta-analysis was conducted using RevMan 5.3 software. A total of 5 RCTs were included, involving 588 patients, with 299 in treatment group and 289 in control group. Meta-analysis results showed that compared with Western medicine alone, Compound Danshen Injection combined with Western medicine was better in the effective rate(RR=1.23,95%CI[1.14,1.33],P<0.000 01), MMSE score(MD=3.54,95%CI[3.01,4.06],P<0.000 01), ADL score(MD=11.49,95%CI[8.05,14.93],P<0.000 01), the level of CRP(MD=-0.72,95%CI[-1.25,-0.20],P=0.007) and the level of IL-6(MD=-7.64,95%CI[-9.65,-5.63],P<0.000 01). Adverse reactions mainly included rash and skin prick, which did not affect the treatment effect. Based on the findings, the combination of Compound Danshen Injection in the treatment of vascular dementia could improve the effective rates, relieve the mental state damage and improve the daily living ability, with mild adverse reactions and a low incidence. However, due to the low quality of the included literatures, high-quality and large-scale randomized controlled trials are needed for further verification.

Differential analysis of different study types in clinical safety evaluation of Xuebijing Injection / 中国中药杂志

This study aimed to comprehensively analyze and compare the differences of different clinical study types currently published in the safety evaluation of Xuebijing Injection. Six databases, namely the Cochrane Library, PubMed, EMbase, CNKI, VIP and Wanfang database, were electronically retrieved to collect all types of studies on the safety of Xuebijing Injection, including randomized controlled trials, case-controlled studies, cohort studies, systematic reviews, and centralized monitoring studies of clinical safety(hospital), in order to comprehensively and objectively evaluate the safety of Xuebijing Injection, and analyze the differences of different research results. A total of 211 literatures were included, involving a total of 46 384 patients treated with Xuebijing Injection, and 423 adverse reactions(ADRs) occurred. They included 191 randomized controlled trials, 3 cohort studies, 15 systematic reviews, and 2 centralized monitoring studies of clinical safety(hospital), and the incidence of adverse reactions was 2.54%(common), 2.31%(common), 0.95%(occasionally), and 0.50%(occasionally). More than half of the 423 cases of ADRs occurred in skin and adnexal system(151 cases) and gastrointestinal system(65 cases), including such manifestations as rash, skin itching, nausea and vomiting, diarrhea. The degree of ADRs was mild. Randomized controlled trials showed that the incidence of ADR was the highest when Xuebijing Injection was used for malignant tumor and multiple organ failure. And the systematic evaluation showed that the incidence of ADR was the highest when Xuebijing Injection was used for spontaneous peritonitis of liver cirrhosis. In conclusion, different study types could lead to significant differences in the results of drug safety evaluation. Sample size, study type, and quality control are the main factors for biased results. Due to large sample size and high-quality, centralized monitoring studies become the better clinical safety evaluation model of drugs at present, and full life cycle management could more objectively reflect drug safety and guide clinical rational drug use.

Urgency of clinical evaluation of traditional Chinese medicine decoction pieces / 中国中药杂志

Decoction piece is the basic unit of traditional Chinese medicine(TCM) prescriptions, and it is also the main material basis for clinical efficacy of TCM. The clinical efficacy of TCM decoction pieces is very important for the overall efficacy of TCM prescriptions. However, the current quality evaluation of TCM decoction pieces mainly focuses on the amount of intrinsic substances and compositions. The basic researches such as toxicology and pharmacology are deeply, but lacking with the evidences from clinical evaluation. Therefore, the current decoction pieces quality evaluation system is difficult to objectively reflect the clinical effect of traditional Chinese medicine, forming the only componential theory or blindly pursuing the large volume and heavy weight of medicine materials. The quality standard of Chinese decoction pieces is biased,with concerns that "TCM will die from Chinese medicine". Therefore, this paper proposes that it is urgent to clinically evaluate the TCM decoction pieces,and regard the clinical evaluation as a starting point and a foothold for the quality evaluation of TCM decoction pieces, based on the origin identification, origin evaluation, product evaluation, content evaluation, and harmful substance detection as an auxiliary support. Finally a new quality evaluation system for TCM decoction pieces with a clinical evaluation as the core is formed, which is composed of six steps, aiming to promote the quality improvement of TCM decoction pieces. Of course, because there is no mature experience in the clinical evaluation of TCM decoction pieces, the quality evaluation system has some challenges such as complex processes and high cost, but it is essential for maintaining the quality of medicinal materials and life safety. Therefore, it is of importance and urgency to construct and implement the quality evaluation system.

A commentary of literature research of traditional Chinese medicine for acute upper respiratory tract infection in children / 中国中药杂志

Acute upper respiratory tract infection is the most common infectious disease in children's respiratory system. The pathogen to the main virus, can account for more than 90% of the primary upper respiratory tract infectio. However, there is no specific anti-viral drugs specifically for the disease, in addition to the existence of excessive, widespread use or even abuse of antibiotics.Long-term clinical practice has confirmed that Chinese medicine is safe and effective in treating acute upper respiratory tract infection in children. The author reviews the literatures of multiple databases, and analyzes the advantages of Chinese patent medicine in the treatment of acute upper respiratory tract infection in children from the perspective of clinical research and experimental basic research. It also puts forward the existing problems and possible research directions of Chinese patent medicine in the treatment of acute upper respiratory tract infection in children.

Efficacy and safety of Lianhua Qingwen capsule for influenza： a systematic review / 中国中药杂志

To evaluate the efficacy and safety of Lianhua Qingwen capsule for influenza. All reports of the randomized controlled trials (RCTs) on Lianhua Qingwen capsule treating influenza were retrieved from database of CNKI, WANFANG DATA, VIP, PubMed, the Cochrane Library by February 2017. The studies were screened according to the inclusion and exclusion criteria, the data were extracted by 2 authors, the quality of the included RCTs was assessed, and meta-analysis was performed using Revman5.3 software. A total of 1 525 patients and 10 studies were included. The results of meta analysis showed that compared with oseltamivir, Lianhua Qingwen capsule was more effective in alleviating flu symptoms, including the time of headaches disappeared [SMD=-0.25,95% CI(-0.48, -0.01)], the time of sore throat disappeared [SMD=-0.53,95% CI（-0.72, -0.34）], the time of cough disappeared [SMD=-0.39,95%CI（-0.57, -0.21）], whole body aches disappeared [ SMD=-0.49, 95% CI (-0.78, -0.21)], the time of weak disappeared [SMD=-0.56,95%CI (-0.82, -0.29)], and the time of abatement of fever [SMD=-3.47,95%CI（-6.27, -0.67）]. Also, there were some statistical significant differences between the two groups except nasal congestion and the time of virus turning negative. Compared with Ribavirin, Lianhua Qingwen capsule was more effective in terms of the rate of temperature effect, [RR=1.53, 95% CI (1.24, 1.90)], the difference between the two groups was statistically significant. Compared with Ankahuangmin capsules, significant differences were found in terms of the he rate temperature effect [RR=1.37, 95%CI (1.19,1.57)]. Current evidence shows that Lianhua Qingwen capsule is more effective and safer than Oseltamivir, Ribavirin and Ankahuangmin capsules. Due to the low quality of the clinical research, the accuracy of this conclusion needs to be conducted to verify.

Systematic review of effectiveness and safety of pudilan Xiaoyan oral liquid in treating pediatric suppurative tonsilitis / 中国中药杂志

The review aims to assess the effectiveness and safety Pudilan Xiaoyan oral liquid in treating pediatric suppurative tonsillitis systematically through searching relevant electronic database and collecting relevant literature. Meta-analysis was performed with the RevMan 5.3 software. Eighteen RCTs of 1 883 patients of pediatric suppurative tonsillitis were included. Meta-analysis showed that： compared with the application of antibiotics alone, combined with Pudilan can effectively improve the treatment of pediatric suppurative tonsillitis in efficacy rate and shorten the time of recovering normal temperature, the time of tonsil purulent discharge and can also reduce the extinction time of sore throat, antiadoncus or congestion subsided and appetite recovery. There was no severe adverse reaction during the treatment. Compared with the application of antibiotics alone, combined with Pudilan may be more effective and safe in the treatment of pediatric suppurative tonsillitis, which can not be strongly proved at present for lack of studies with high quality.

Lanqin oral liquid for the treatment of chronic pharyngitis：systematic review and Meta-analysis of randomized clinical trials / 中国中药杂志

To systematically assess the effectiveness and safety of lanqin oral liquid for the treatment of chronic pharyngitis. Databases including PubMed, Embase, The Cochrane Library, SinoMed, CNKI, VIP and Wanfang Data were electronically searched in March 2017 for randomized controlled trials(RCTs) on Lanqin oral liquid for the treatment of chronic pharyngitis. Two authors independently screened literature, extracted data, and assessed the risk of bias of included studies. Then, meta-analysis was performed by RevMan 5.3 software. Thirteen RCTs were included with a total of 1 642 patients. The results of meta-analysis showed that the efficiency of lanqin oral liquid were significantly higher than those of conventional therapy or other treatments; Besides, lanqin oral liquid could significantly increase the amount of IL-2 further more, lanqin oral liquid could significantly reduce the amount of TNF-α. Safety of lanqin oral liquid was not concerned by any RCT. Current evidence indicates that the efficiency of lanqin oral liquid was better than conventional therapy or other treatments. Due to the poor quality of the included studies, the above conclusion should be verified by more RCTs of high quality.

Huoxiang Zhengqi formulas for treatment of gastrointestinal type cold：a systematic review and Meta-analysis / 中国中药杂志

This systematic review aims to evaluate the efficacy and safety of Huoxiang Zhengqi formulas in treating gastrointestinal type cold. Seven electronic databases,including CNKI, WanFang Data, Vip, SinoMed, PubMed, Cochrane Library, Embase will be searched from the inception of the study until March 2017.All randomized controlled trials that evaluate the treatment of Huoxiang Zhengqi formulas for gastrointestinal type cold will be eligible. The methodological quality will be assessed using the Cochrane risk of bias tool for randomized clinical trials and Review Manager 5.3 software is used for analyzing the data.The results are： eight RCTs and 680 patients are included .Meta-analysis are performed according to the stratification of the treatment strategy. Eight studies report clinical efficacy, among them four studies show Huoxiang Zhengqi formulas are better than western medicine(RR and 95%,1.2[1.08, 1.33]), another four studies showHuoxiang Zhengqi formulas in conjunction with conventional treatment are better than conventional treatment(RR and 95%, 1.32[1.20,1.46]).About symptom remission rate, one study shows the treatment group effect is better than the control group from the following clinical symptoms：chills,fever,bowel diarrhea,the effect of treating sore throat itchy is same with western medicine treatment.No adverse reactions are found about Huoxiang Zhengqi formulas in this study.Current evidence shows that Huoxiangzhengqi formulas are better than Western medicine group and western medicine routine treatment group from clinical efficacy. Limited by the quantity and quality of studies, more large-scale and rigorously designed randomised controlled trials with large sample size are warranted to clarify the conclusions.

Expert consensus on the design and implementation of clinical safety centralized monitoring study of Chinese medical injection / 中国中药杂志

Along with the increase of clinical application, the safety of traditional Chinese medicine gained more and more attentions. In particular, the safety evaluation of Chinese medical injections has become a mandatory task should be completed by pharmaceutical companies under the supervision of China Food and Drug Administration(CFDA). Due to the weak foundation of previous studies, the safety issues of Chinese medical injections have not been fully understood, and lack of scientific and rational risk management programs. Clinical safety centralized monitoring(CSCM) is an important method for post-market safety evaluation of Chinese medicine. Due to the lack of appropriate norms and procedures, the quality of similar research is uneven, and the results vary. Combined with practical experience with experts' suggestions, we developed this expert consensus on the design and implementation of CSCM from three stages (design, implementation and report) with 20 technical points, which will provide technical support for future CSCM studies.

Guizhi Fuling capsule / pill treatment for chronic pelvic inflammatory disease：a systematic review of randomized clinical trials / 中国中药杂志

This systematic review aims to systematically evaluate the efficacy and safety of Guizhi Fuling Capsule/Pill on the treatment of chronic pelvic inflammatory disease. We searched CNKI datebases,WanFang,SinoMed,PubMed,Embase,The Cochrane Library from the inception to February 2017,to collect randomized controlled trials（RCTs）of Guizhi Fuling Capsule/Pill in treating chronic pelvic inflammation disease.Two reviewers independently screened literature,extracted date and assessed the risk of bias of included studies.Then,the risk assessment of included references was evaluated according to criteria recommended by Cochrane Handbook 5.3.A total of 30 RCTs involving 3 586 patients were finally included.30 studies reported the clinical efficacy,the result of meta-analysis showed that：compared with the western medicine group,Guizhi Fuling (capsule,pill) combined with western medicine could significantly improve the clinical efficacy [RR=1.20,95%CI（1.16,1.23）];3 studies reported recurrence rate,the result of meta-analysis showed that：compared with the western medicine,Guizhi Fuling (capsule,pill) combined with western medicine could decrease the recurrence rate [RR=0.33,95%CI（0.18,0.62）]; Their secondary indicators mainly included hs-CRP, plasma viscosity ratio and tumor necrosis factor and fibrin,the result of meta-analysis showed that： Guizhi Fuling (capsule,pill) combined with western medicine was better than western medicine in terms of anti-inflammatory and improving blood circulation.17 studies reported adverse reactions,most of the adverse events were the irritation of gastrointestinal tract. The result showed that： compared with the western medicine group, the incidence of adverse reactions in Guizhi Fuling (capsule,pill) combined with western medicine group is low.Guizhi Fuling（capsule,pill） did not increase the adverse reactions. The available evidence suggests that： Guizhi Fuling（capsule, pill） compared with the western medicine group, Guizhi Fuling (capsule,pill) combined with western medicine was more effective than the western medicine group in terms of clinical efficacy, recurrence rate, anti-inflammatory and plasma viscosity.Due to the limited quality and quantity of included studies,more high quality RCTs are needed to verify the above conciusion.

Establish research model of post-marketing clinical safety evaluation for Chinese patent medicine / 中国中药杂志

The safety of Chinese patent medicine has become a focus of social. It is necessary to carry out work on post-marketing clinical safety evaluation for Chinese patent medicine. However, there have no criterions to guide the related research, it is urgent to set up a model and method to guide the practice for related research. According to a series of clinical research, we put forward some views, which contained clear and definite the objective and content of clinical safety evaluation, the work flow should be determined, make a list of items for safety evaluation project, and put forward the three level classification of risk control. We set up a model of post-marketing clinical safety evaluation for Chinese patent medicine. Based this model, the list of items can be used for ranking medicine risks, and then take steps for different risks, aims to lower the app:ds:risksrisk level. At last, the medicine can be managed by five steps in sequence. The five steps are, collect risk signal, risk recognition, risk assessment, risk management, and aftereffect assessment. We hope to provide new ideas for the future research.