临床定位是药品在拟定目标适应证中预期的治疗作用,临床定位准确是新药研发成功和上市后临床合理用药的关键.在中药新药临床定位时,需要从研究药物、目标疾病、已有治疗措施和审评要求等维度评估合理性.临床定位的方法与依据包括人用经验、中医药理论、基础研究和临床试验等.以临床价值为导向,选定合理的临床定位,才能真正体现中药的疗效,提高中药新药的研发质量和成功率.

It was pointed out in Opinions on Promoting the Inheritance, Innovation and Development of Traditional Chinese Medicine issued by the State Council in 2019 that 100 varieties of traditional Chinese medicine(TCM) with unique curative effects should be screened out within about three years. Due to the multi-component and multi-target mechanisms of TCM varieties, it is difficult to directly and simply evaluate their multi-dimensional clinical value using methods applicable to chemical or biological agents. The heterogeneity of outcomes for similar TCM makes it difficult to determine the advantages of similar products. The fuzzy comprehensive evaluation method that is developed on the basis of core outcome set and fuzzy mathematics for clinical efficacy evaluation of TCM may solve these problems. This study developed a fuzzy comprehensive evaluation model for the clinical efficacy evaluation of Chinese patent me-dicines for coronary heart disease and angina pectoris, and selected the previous normative studies with complete or incomplete data for verifying the model application. The results showed that original studies with complete data failed to evaluate and compare the comprehensive efficacy of different interventions. The original research only mentioned the advantages and disadvantages of different interventions in different aspects. The comprehensive clinical efficacy of three different interventions obtained through fuzzy comprehensive evaluation was all graded as level Ⅱ. The original research with incomplete data drew the same conclusions as the fuzzy comprehensive evaluation, and the results of fuzzy comprehensive evaluation can provide more comprehensive information. Therefore, the fuzzy comprehensive evaluation shows the products with overall advantages of clinical efficacy, which may become a feasible method for the screening of TCM.

目的 探讨中药临床研究联合用药安全性评价方法,以满足临床安全、有效用药的需求.方法 从中药临床研究入手,分析中药临床研究联合用药安全性存在的问题,并对其关键问题提出适当的建议.结果 中药联合用药安全性评价体系需要建设和完善.结论 中药联合用药的安全性评价需要从研发早期开始,贯穿临床试验至上市后评价的药品全生命周期;重视研究设计和风险-获益评估,搭建研究设计-监测评价-分析预测-风险管理的动态研究模式,建立多学科的综合评估体系.

中药新药研发与临床研究是对科学性与操作性具有较高要求,受到政策法规、疾病研究进展、科学技术创新与发展深度影响的领域,需要“政产学研用”的系统协作.合同研究组织作为药物研究生态链中的一环,在新药研发,特别是临床研究中发挥着重要作用.本文从致力于中医药临床研究的合同研究组织近20年的实践经验出发,对取得成功的经验与案例及遇到的挑战与困难进行讨论,以期能够抛砖引玉,有益于促进中药新药研发与临床研究的健康发展.

目的 探讨尪痹片联合甲氨蝶呤片治疗类风湿关节炎(RA)患者的有效性和经济学.方法 选择病情处于活动期的RA患者360例,随机分为试验组与对照组,每组180例.试验组选用尪痹片联合甲氨蝶呤片,对照组选用甲氨蝶呤片,进行有效性评价,运用药物经济学的成本-效果分析方法对各组进行评价及敏感性分析.结果 试验组较对照组的疾病活动度降低,疾病控制更好,差异有统计学意义(P<0.05).试验组成本为947.54元,对照组成本为142.87元,对照组的各项药品C/E和总成本C/E低于试验组.每增加一个疗效单位,试验组疗效-成本最高的指标是疾病活动度评价(DAS28评分),每提高1分消耗2299.06元,疗效-成本最低的指标为ACR20,每提高1％消耗63.56元.敏感性分析结果与基础分析一致.结论 尪痹片联合甲氨蝶呤片治疗RA可以提高临床疗效,虽然需要增加成本,但是增量成本-效果分析结果表明,增加疗效产生的费用具有成本-效果优势.

BACKGROUND:Although we have made tremendous medical advances in recent decades in modern antibiotics and supportive therapies, the treatment of sepsis has not experienced such rapid advancement. Xuebijing injection (XBJ) is a Chinese prescription consisting of Carthamus tinctorius, Radix paeoniae rubra, Ligusticum wallichii, Radix salviae miltiorrhizae and Radix angelicae sinensis. Clinical experience suggests that XBJ may provide a solution in the management of sepsis. However, the safety of this treatment is still controversial. This study aims to detect the occurrence of XBJ-related adverse drug reactions (ADRs) among individuals in clinical practice.METHODS:From the clinical application of XBJ in a real-world setting, patients in 93 hospitals using XBJ were monitored between August 2013 and August 2016. There was no limit on the treatment course and dosage. From data obtained in interviews or telephone follow-ups with hospitalized patients, the circumstances of patients' adverse events (AEs) during the course of drug treatment and during the 7 days after drug withdrawal were recorded and encoded by MedDRA18.0. The likelihood of ADRs was determined by the criteria of the Uppsala Monitoring Centre. Statistical analyses were performed by SAS9.2 software.RESULTS:In total, 31,913 participants enrolled, and none were lost to follow-up. AEs (suspected ADRs) occurred in 234 participants. ADRs occurred in 96 participants, and the incidence was 0.3%. The ADRs with the top three frequencies were skin pruritus (0.116%), erythra (0.066%) and chest tightness (0.044%). There was no significant relationship between ADRs and solvents (P=0.149), route of administration (P=0.640), unhealthy addiction (P=0.069), allergy (P=0.535), first use of XBJ (P=0.161) or dosage (P=0.743). There was a significant relationship between ADRs and irrigating syringe (P<0.0001) and fluid dripping too quickly (P=0.019).CONCLUSIONS:This large-scale survey of hospitalized patients found that the incidence of ADRs was occasional (0.3%), while most of the ADRs were relatively mild or non-serious. XBJ should be administered rationally and according to its instructions to prevent the occurrence of ADRs.

Ethnopharmacological relevance: Xuebijing injection (XBJ), a Chinese patent medicine that was approved for treating sepsis in China in 2004, consists of Carthamus tinctorius L. (Carthami Flos, hong hua), Paeonia lactiflora Pall. (Paeoniae Radix Rubra, chi shao), Ligusticum chuanxiong Hort. (Chuanxiong Rhizoma, chuan xiong), Salvia miltiorrhiza Bge. (Salviae Miltiorrhizae Radix Et Rhizoma, dan Shen) and Angelica sinensis (Oliv.) Diels (Angelicae Sinensis Radix, dang gui). Aim of the study: This study aimed to assess the efficacy and safety of XBJ combined with routine treatment (RT) for treating sepsis through systematic review and meta-analysis. Materials and methods: Databases including Embase, PubMed, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Database (VIP) and the Wanfang database were searched from inception to June 6, 2017 to collect relevant RCTs comparing XBJ combined with RT and RT alone for sepsis. The primary clinical outcomes were 28-day mortality and mortality during treatment. The secondary outcomes of our study included APACHE II scores, WBC counts, body temperature, and adverse events or reactions. We excluded low-quality studies (Jadad score < 3) and calculated risk ratios (RR) for primary outcomes with fixed effects models. We assessed quality of evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. Results: We identified 1602 records, and 16 RCTs (1144 patients) were included. Moderate-quality evidence suggested that combined therapy reduced 28-day mortality (934/1144, RR 0.62, 95% CI 0.51-0.76 P < 0.000 01, I-2 = 0%), APACHE II scores (792/1144, MD -3.53, 95% CI -4.49 to -2.54; P < 0.000 01, I-2 = 59%) and body temperature (362/1144, MD -0.43, 95% CI -0.55 to -0.31; P < 0.000 01, I-2 = 0%). Very low-quality evidence showed that WBC count improved with combined medication at high dosages (one study included, 40/1144, MD -8.00, 95% CI -10.18 to -5.82), but there was no reduction at moderate dosages (230/1144, MD -2.38, 95% CI -5.01 to 0.25; P = 0.08, I-2 = 70%). However, moderate-quality evidence indicated positive results with low dosages (142/1144, MD -2.88, 95% CI -3.79 to -1.96; P < 0.000 01, I-2 = 0%). Nevertheless, due to the insufficient number of studies and the poor quality of the current evidence, more studies of dose-effect relationships and safety concerns of XBJ are needed. Low-quality evidence showed no risk difference for mortality during treatment (210/1144, RR 0.65, 95% CI 0.36-1.17; P = 0.15, I-2 = 0%). Conclusions: This study suggested that supplementation with XBJ in addition to regular treatment may improve the 28-day mortality rate, APACHE II scores, WBC count and body temperature of sepsis patients without serious adverse events, but it may not reduce mortality during treatment, revealing a specific, remote effect of traditional Chinese medicine. However, given the high risk of bias and the low quality of the included trials, we may be unable to draw any conclusions about its routine use. Rigorously designed, multicentre, large-scale, methodologically sound trials are warranted.

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.

OBJECTIVE:To assess the efficacy and safety of Xuebijing injection for the treatment of severe acute pancreatitis ( SAP ).METHODS:An extensive search of related literatures from the Cochrane Library, EMBASE, China Biology Medicine ( CBM ), CNKI, VIP and Wanfang data up to March 2014 was performed. Randomized controlled trials ( RCTs ) regarding Xuebijing injection for the treatment of SAP were collected regardless of languages. Jadad scale was taken for quality evaluation of the included studies by two researchers. The patients in control group were given conventional treatment, and those of the Xuebijing group were given Xuebijing injection on the top of conventional treatment. The Cochrane Collaboration RevMan 5.2 software was used for data analysis regarding the effect of Xuebijing injection on the mortality, incidence of complication, effective rate, the length of stay in hospital, and the safety of the drug in patients with SAP.RESULTS:A total of 15 published reports meeting the inclusion criteria were enrolled. The methodological quality of the trials was low. Meta analysis showed that the mortality in Xuebijing group was significantly lower [ odds ratio ( OR ) = 0.37, 95% confidence interval ( 95%CI ) = 0.17 - 0.77, P = 0.008 ], and the incidence of complication was also significantly decreased ( OR = 0.26, 95%CI = 0.14 - 0.45, P < 0.000 01 ) as compared with those of control group. The effective rate in Xuebijing group was significantly higher than that of the control group [ relative risk ( RR ) = 0.85, 95%CI = 0.80-0.91, P < 0.000 01 ]. The length of stay in hospital in Xuebijing group was significantly shorter than that of the control group [ mean difference ( MD ) = -5.28, 95%CI = -6.69 to -3.86, P < 0.000 01 ]. Adverse reactions of Xuebijing injection were reported in 2 studies. The adverse reaction in one study was headache and nausea, which were relieved by adjusting the speed of intravenous infusion, and mild rash was reported in another case, and it disappeared after the withdrawal of Xuebijing.CONCLUSIONS:The currently available evidence shows that Xuebijing injection may have some therapeutic effect on SAP. Because of the low methodological quality of the included trials, multi-center and high-quality RCTs with large sample sizes are needed to provide stronger evidence.

To learn about the economic studies on traditional Chinese medicines in domestic literatures, in order to analyze the current economic assessment of traditional Chinese medicines and explore the existing problems. Efforts were made to search CNKI, VIP, Wanfang database and CBM by computer and include all literatures about economic assessment of traditional Chinese medicines published on professional domestic journals in the systematic assessment and quality evaluation. Finally, 50 articles were included in the study, and the systematic assessment and quality evaluation were made for them in terms of titles, year, authors' identity, expense source, disease type, study perspective, study design type, study target, study target source, time limit, cost calculation, effect indicator, analytical technique and sensitivity analysis. The finally quality score was 0.74, which is very low. The results of the study showed insufficient studies on economics of traditional Chinese medicines, short study duration and simple evaluation methods, which will be solved through unremitting efforts in the future.

At present, diabetes is a chronic disease of great cost and heavy burdens. The International Diabetes Federation has repeatedly warned that by 2025, the global number of diabetics would rise to 333 million from 194 million in 2003. Although the occurrence of diabetes in developing countries is lower, China has a large population, so that the number of cases is increased. At the same time, more people have prediabetes, a growing health concern where a large percentage of the patients develop full type 2 diabetes. In addition, the patients of diabetes easily incur complications such as blindness, kidney failure, and cardiovascular diseases that can seriously affect the patients’ quality of life and cause great economic burdens to family and society. Therefore, effective interventions for prediabetes are needed to prevent or delay the occurrence and development of diabetes.

Objective. To summarize the characteristics and analysis of relevant factors and to give references for prevention and further study of liver damage associated with Polygonum multiflorumThunb. (HSW), we provide a systematic review of case reports and case series about liver damage associated with HSW. Methods. An extensive search of 6 medical databases was performed up to June 2014. Case reports and case series involving liver damage associated with HSW were included. Results. This review covers a total of 450 cases in 76 articles. HSW types included raw and processed HSW decoction pieces and many Chinese patent medicines that contain HSW. Symptoms of liver damage occur mostly a month or so after taking the medicine, mainly including jaundice, fatigue, anorexia, and yellow or tawny urine. Of the 450 patients, two cases who received liver transplantation and seven who died, the remaining 441 cases recovered or had liver function improvement after discontinuing HSW products and conservative care. Conclusion. HSW causes liver toxicity and may cause liver damage in different degrees and even lead to death; most of them are much related to long-term and overdose of drugs. Liver damage associated with HSW is reversible, and, after active treatment, the majority can be cured. People should be alert to liver damage when taking HSW preparations.

Objective. To systematically collect evidence and evaluate the effects of Danhong injection (DHI) for unstable angina (UA).Methods. A comprehensive search was conducted in seven electronic databases up to January 2015. The methodological and reporting quality of included studies was assessed by using AMSTAR and PRISMA.Result. Five articles were included. The conclusions suggest that DHI plus conventional medicine treatment was effective for UA pectoris treatment, could alleviate symptoms of angina and ameliorate electrocardiograms. Flaws of the original studies and systematic reviews weaken the strength of evidence. Limitations of the methodology quality include performing an incomprehensive literature search, lacking detailed characteristics, ignoring clinical heterogeneity, and not assessing publication bias and other forms of bias. The flaws of reporting systematic reviews included the following: not providing a structured summary, no standardized search strategy. For the pooled findings, researchers took statistical heterogeneity into consideration, but clinical and methodology heterogeneity were ignored.Conclusion. DHI plus conventional medicine treatment generally appears to be effective for UA treatment. However, the evidence is not hard enough due to methodological flaws in original clinical trials and systematic reviews. Furthermore, rigorous designed randomized controlled trials are also needed. The methodology and reporting quality of systematic reviews should be improved.

Rhizoma Coptidis (Huang Lian in Chinese pinyin) is among the most widely used traditional Chinese herbal medicines and has a profound history of more than 2000 years of being used as a therapeutic herb. The antidiabetic effects of Rhizoma Coptidis have been extensively investigated in animal experiments and clinical trials and its efficacy as a promising antihyperglycemic agent has been widely discussed. In the meantime, findings from modern pharmacological studies have contributed the majority of its bioactivities to berberine, the isoquinoline alkaloids component of the herb, and a number of experiments testing the antidiabetic effects of berberine have been initiated. Therefore, we conducted a review of the current evidence profile of the antihyperglycemic effects of Rhizoma Coptidis as well as its main component berberine and the possible mechanism of actions, in order to summarize research evidence in this area and identify future research directions.

IntroductionTraditional Chinese medicine (TCM) has accumulated some experience in curing stable angina pectoris (SAP) and efficacy has been demonstrated. Chinese patent medicines, known as modern dosage forms of TCM, can attain the desired effect in clinical application only with the guidance of TCM syndrome theory. However, due to their use by a large number of persons with little knowledge of TCM theories and practices, their efficacy and reputation have been seriously affected.Method and analysisTwo common syndrome types of SAP in TCM, ‘qi deficiency and blood stasis’ and ‘qi stagnation and blood stasis’, will be studied in 144 subjects from four TCM hospitals in Tianjin in China using a partial crossover design. The two syndromes will be broken down into six symptom combinations; patients will select a combination of the most distressing to them, and then will be randomised into two groups. Each group, on the basis of routine medication, will be administered one kind of Chinese patent drug: Qishenyiqi Dripping Pills or Compound Danshen Dripping Pills. The treatment characteristics of the two medicines will be evaluated with the COME-PIO method developed by our research team.Ethics and disseminationThis protocol has been approved by the medical ethics committee of Tianjin University of TCM (registration number TJUTCM-EC20130005). The study is safe and reliable.Trial registration numberChinese clinical trials register ChiCTR-TTRCC-14004406.

The practice of traditional Chinese medicine (TCM) has a profound history in many Asian countries. TCM syndrome is a set of characteristic physical signs and symptoms shared by a group of patients. Syndrome diagnosis and treatment assignment according to the identified TCM syndrome is a long-held practice of Chinese medicine. Owing to its distinctive way of interpreting illness and administering care, medical practitioners not well educated in TCM theories and practices are generally incapable of giving out prescriptions for Chinese patent drugs. Currently, the existence of a multitude of Chinese patent drugs marked with largely identical indications is further complicating this situation.