Preliminary Discussion on Post-marketing Comprehensive Evaluation Indicator System of Ancient Famous Classical Formula Preparations / 中国实验方剂学杂志

The construction of the comprehensive evaluation index system of the famous classical formula preparations after the marketing has both theoretical and practical significance. In this study， literature related to the post-marketing comprehensive evaluation of traditional Chinese medicine（TCM） compound preparations was retrieved from China National Knowledge Infrastructure（CNKI）， China Science and Technology Journal Database（VIP）， Wanfang Data Knowledge Service Platform（WanFang） and SinoMed from January 1， 2000 to April 30， 2022. CiteSpace 6.1.R2， a scientometrics software， was used to visualize the keywords involved， and to analyze the dynamic evolution trend and research hotspots in this field. Then， the existing comprehensive post-marketing evaluation index system of TCM compound preparations was screened and extracted， and the research status was systematically analyzed by mathematical statistics. It was found that there were problems such as the generalized boundaries between assessment dimensions and assessment elements， the lack of data sources for individual evaluation indexes， unset weight of some index system and insufficient application degree. In addition， according to the characteristics of famous classical formulas， the authors discuss the importance of evidence evaluation based on combination of disease and syndrome， pharmacovigilance of famous classical formulas preparations， and whole-process quality control of famous classical formulas， and put forward the construction strategy of comprehensive post-marketing evaluation of the famous classical formula preparations， which is oriented by clinical value， centered on evidence evaluation， and guaranteed by the whole-process quality control.

Key points of post-marketing evaluation of classic traditional Chinese medicine prescriptions based on combination of disease and syndrome / 中国中药杂志

Classic prescriptions, hospital preparations and famous traditional Chinese medicine(TCM) experience prescriptions are the main sources of new drug development and innovation. The multi-components and multi-targets treatment characteristics of TCM are advantages, but at the same time, broad indications, unclear clinical positioning and lack of evidence-based evidence support are the key problems affecting the play of TCM efficacy and restricting its promotion and application. The hot in recent research was to how to break through the bottleneck, precise clinical positioning, highlight the advantages of the classic TCM prescriptions, and complete the transformation from clinical practice, clinical research to clinical evidence, but at the same time, it is also the difficulty. The clinical research model of the combination of disease and syndrome can fully reflect the ancient medical case evidence of classic TCM prescriptions, the historical experience of human used and the characteristics of syndrome differentiation and treatment, and highlight the advantages of Chinese medicine. At the same time, under the modern disease classification system and research mode, is conducive to established the standardized clinical evidence report and evaluation system, is conducive to promote the integration of clinical research evidence, and avoids excessive attenuation of information. Based on the previous work of our team, the intention of this study was to make a comment about the key points of the post-marketing evaluation of the classic TCM prescriptions under the combination of disease and syndrome and includes key points:(1)With the syndrome as the carrier, connected with the classical prescription and clinical diseases, focused on the clinical positioning on macroscopically.(2)The combination of syndrome visualization, standardization and pharmacological molecular basis, focus on clinical precise positioning in microscopic.(3)Innovating therapeutic effect evaluation methods, reflecting the curative effect characteristics based on syndrome differentiation.(4)The combination of "randomized controlled evidence-based studies" and "real world evidence-based evaluation", focusing on clinical advantages, fully evidence-based evidence.(5)Make full use of clinical registration studies and pay attention to safety.

Application of objective performance criteria in post-marketing evaluation schemes of traditional Chinese medicine / 中国中药杂志

Traditional Chinese medicines(TCMs) have certain limitations in the clinical research design in their post-marketing evaluation, so that randomized controlled programs cannot be strictly implemented in some studies, while the objective performance criteria is a reasonable external controlled research method that has been gradually recognized at home and abroad in recent years in addition to randomized controlled trial(RCT) method. It is more mature in medical devices, surgery and other research fields, but there is no relevant report in the field of post-marketing evaluation of Chinese patent medicines. In this paper, the application prospect of the objective performance criteria and the problems were discussed in the field of post-marketing evaluation of TCM. The characteristics of as TCM are more consistent with the scope of the objective performance criteria, the application of the objective performance criteria in post-marketing evaluation of Chinese patent medicines, especially in single arm research, can break through the limitations of existing conventional clinical research methods, and improve the level of evidence, with good feasibility and advantages. However, in the application process, we should pay attention to the key issues such as the selection of index, research population, follow-up period and the reference selection, to ensure the quality of research. This research group has carried out some exploration and practice in the field of post-marketing evaluation of TCM injections by using single arm combined with the objective performance criteria, hoping to establish the key technology in this field, and provide certain research and design reference for the secondary development of Chinese patent medicines.

Application of add-on-design in post-marketing evaluation of traditional Chinese medicine / 中国中药杂志

Post-marketing evaluation of traditional Chinese medicine(TCM) is an important research stage in the life cycle of a drug, and the add-on-design is a common method for its post-marketing evaluation. This article introduces the basic concept of add-on-design, and points out that it is suitable for use based on the principles of medical ethics when the standard treatment should not be interrupted. The post-marketing evaluation of TCM should be carried out based on human experience and in compliance with regulations and ethics. The clinical values of TCM, such as the therapeutic effect for disease, improvement of disease symptoms, improvement in quality of life, as well as the synergism and toxicity attenuation of combined use of TCM and chemical drugs, should be fully reflected through the clinical trials designed with add-on-design. The key points of add-on-design are accurate clinical positioning, scientific estimation of sample size, and rigorous standard treatment. Standard treatment should be a recognized one, consistent and stable; appropriate and recognized efficacy indicators and targeted safety indicators should be selected; the design and operation of clinical research scheme should meet the requirements of randomization and blind method, with special emphasis on the production of qualified placebo. The add-on-design has the advantages that the rights and interests of the subjects are adequately protected. Besides, the research conclusions are easily put into clinical application. But there are also many difficulties, such as the influence of confounding bias, the "ceiling" effect of clinical efficacy, and the difficulty of interpretation of adverse events. Therefore, a rigorous research quality assu-rance system should be established, and the quality control of evaluation consistency of researchers should be emphasized to ensure strict quality control in the research process.

Thoughts on post-marketing evaluation of classical Chinese patent medicines based on clinical value / 中国中药杂志

Classical Chinese patent medicines(CPMs) are a kind of modern preparation developed from the experience of compatibility and application about ancient prescriptions. Its rich history of human use and reliable clinical efficacy imply the unique theoretical essence and precious value of traditional Chinese medicine(TCM). With the development of evidence-based medicine and the improvement of medical policy, it is particularly urgent to evaluate the clinical values of post-marketing classical CPMs. In this paper, some problems on the clinical value evaluation of CPMs would be described, and it is considered that the simplified evaluation procedures can lead to the lack of evidence for evaluating clinical value of CPMs, causing the difficulty in evaluating the quality of CPM, lack of R&D motivation of enterprises, low content of science and technology, and poor international development. Based on this background, it points out that the clinical value evaluation is the core of the post-marketing evaluation of the classical CPMs, and the eva-luation should be based on the direction of literature research and the latest practice. We should adhere to the research mode of combination disease with syndrome, and select the appropriate type of trials, with clinical efficacy, health economic benefits and safety eva-luation as the main content of the studies, in order to refine the indications and standardize the clinical positioning. Clinical value eva-luation is the basis and main content of post-marketing comprehensive researches on classic and famous CPMs to clarify their clinical value, obtain the conditions for continued marketingand standardize their clinical application, so as to optimize the evidence and quality service of classic and famous CPMs and inherit the core value concept of Chinese medicine.

Exploration and practice of post-marketing survival benefit evaluation of Chinese patent medicine for cancer / 中国中药杂志

Traditional Chinese medicine(TCM) is an important feature of cancer treatment in China. The methods to tap the advantages of TCM, reasonably evaluate and accurately apply Chinese patent medicines have become current research hotspots and difficulties. TCM takes syndrome differentiation and treatment as the core, with the characteristics of overall regulation and multi-targets efficacy. Therefore, the post-marketing survival benefit evaluation of Chinese patent medicines for cancer is different from that in modern medicine. The primary treatment goals in cancer patients include to improve the disease control rate and prolong their survival time. At present, Chinese patent medicines for cancer patients are lacking indepth studies on survival benefit at the post-marketing stage. In addition, the characteristics of individualized treatment with TCM have also increased the complexity of clinical research on TCM. Therefore, it is of certain practical significance and necessity to evaluate the survival benefit of Chinese patent medicines for cancer after marketing. Based on this, in this paper, we first summarized the technical methodological means of survival benefit evaluation at this stage, and then explored the post-marketing survival benefit evaluation of Chinese patent medicines for cancer from three aspects: the evaluation of cancer treatment effect based on survival time and quality of life, treatment-related toxicity and the auxiliary effect of TCM, and the improvement effect for tumor-related symptoms. Based on the practices of early clinical researches, and according to the insufficient efficacy evaluation of current clinical research on Chinese patent medicines, this paper proposed to improve the evaluation system for clinical researches on Chinese patent medicines, establish the evaluation method with TCM characteristics, clarify the dominant population, lay a theoretical foundation for the evaluation of post-marketing survival benefits of Chinese patent medicines for cancer in the future, and promote the modernization process of TCM.

Conception and practice of "three dimensions and four stages" clinical orientation method for post-marketing evaluation of traditional Chinese medicine / 中国中药杂志

The article summarized the relevant researches on the clinical orientation of Chinese patent medicines, and put forward the post-marking principle and strategies of the clinical orientation. The principle could be illustrated by four criteria: overall design, step-by-step implementation, from easiness to hardness, gradual concentration. The strategies were as follows: first carrying out the projects with little cost of money and time, and then the projects requiring much cost of money and time, so that the possibility of fai-lure would be put forward at an early stage to reduce the loss caused by research failure as much as possible by consolidating the research projects with less investment at the early stage and gradually increasing the research projects with more investment at the later stage. On this basis, the "three dimensions and four stages" key technology was proposed for the post-marketing clinical orientation of traditional Chinese medicine. Medicines, diseases and patients were the "three dimensions", so we should understand the features and interaction of the target indications, symptoms and population to establish a three-dimensional clinical positioning coordinate system. "Four stages" were the four steps of clues analyzing, hypothesis orientation, preliminary verification and clinical validation. Each latter stage should be started after full completion of the former one, and the latter stage results shall be used to validate and revise the former clinical orientational hypothesis, continuously forming a feedback circle. Based on the sufficient verification of previous study, prospective clinical trials were implemented at last to get the best evidence-based evidence of clinical orientational hypothesis.

Study on precise mechanism of Chinese patent medicine from perspective of activating data / 中国中药杂志

Traditional Chinese medicine(TCM) syndrome differentiation and treatment has a characteristic and advantageous efficacy in the prevention and treatment of major diseases(no matter for new or sudden infectious diseases or major chronic diseases). At present, the clinical application by Western medicine disease's name, stage, classification and other indications limits the role of TCM syndrome differentiation and treatment, and makes TCM difficult to play its advantages. Therefore, the therapeutic value and social value attribute of Chinese patent medicine after being launched in the market cannot be effectively demonstrated, or even generalized as adjuvants. Under the circumstances, it is difficult to put forward precise positioning different from chemical drugs, with fewer high-level and high-quality evidence-based evidences for precise positioning. The research on the pathological links and therapeutic mechanism of its effect on diseases is also less systematic. The development of biotechnology, such as genomics, has brought medicine into the era of precision, providing ideas and technical support for the exploration of syndrome biomarkers and the analysis of therapeutic mechanism with them as parameters. Digital China Think Tank Forum once mentioned that the development of sequencing technology provides 100% of human genetic code, while only 3% can understand it. Block data 4.0: activation data in the era of artificial intelligence puts forward the concept of activation data, which can be regarded as a theoretical hypothesis for big data, provides a new cognitive thinking and solution for increasingly prominent data paradox between bioinformation explosion and clinical big data, and is a bridge between cross-border data association and fusion. After deeply mining the dominant and recessive value of clinical data and histological data, we can make the pathogenesis of syndrome differentiation and treatment from dark knowledge to clear knowledge. Therefore, with Chinese patent medicine as the guide, the research on the efficacy and mechanism of precise positioning of traditional Chinese medicine after marketing is carried out, and the precise system of "syndrome, disease, function, pathological link and biological connotation" is constructed, which provides a powerful basis and support for increasing the scientific and technological content of varieties.

Post-marketing pharmaco-economics evaluation of Jinye Baidu Granules / 中国中药杂志

To evaluate the economy and applicability of Jinye Baidu Granules in the treatment of acute upper respiratory tract infection, a randomized, double-blind, positive drug parallel control clinical trial was conducted in this study. Stratified block random, double-blind and double simulation test was used. The experimental group took Jinye Baidu Granules, 10 g/time, three times a day, and Compound Shuanghua Granules placebo, 6 g/time, four times a day. The control group took Compound Shuanghua Granules, 6 g/time, 4 times a day, and Jinye Baidu Granules placebo, 10 g/time, 3 times a day. The course of treatment was 5 days. The total cost of this study included direct medical cost and indirect medical cost. The incremental cost-effect analysis method was used for evaluation. Treeage Pro software was used to build a pharmaco-economics model and make statistical analysis. Patients from 10 hospitals were divided into experimental group(304 cases) and control group(302 cases). The baseline values of age, sex ratio, clinical symptoms and signs scores, and important physical examination indexes of the two groups were compared. After 5 days of treatment, the cost per capita of the experimental group was(388.06±94.17) Yuan, and that of the control group was(378.47±95.46) Yuan. The cost of direct medical treatment per capita was(271.24±54.11) Yuan for the experimental group and(264.88±112.71) Yuan for the control group. The average cost of indirect medical treatment was(116.82±82.75) Yuan in the experimental group and(113.59±87.77) Yuan in the control group, with no significant difference in the cost of medical treatment per capita, the cost of direct medical treatment per capita and the cost of indirect medical treatment per capita between both groups. The results of incremental cost-effect analysis based on the total score difference in symptoms and signs after 5 days of treatment showed that ICER=23.39 Yuan/score, which was less than the willingness to pay 100 Yuan/score determined through expert interviews. The experimental group had economic advantages over the experimental group, with the economic probability of 53%. Sensitivity analysis supported the robustness of the results. The results of incremental cost-effect analysis based on the total recovery rate of symptoms and signs showed that compared with the experimental group, the control group had lower cost, better effect and absolute economic advantage, with a corresponding probability of 55%. Based on the above results, it is concluded that there is no significant difference in economic outcome between Jinye Baidu Gra-nules and Compound Shuanghua Granules in the treatment of acute upper respiratory tract infection.

Post-marketing Re-evaluation of Tongxiening Granules () in Treatment of Diarrhea-Predominant Irritable Bowel Syndrome: A Multi-center, Randomized, Double-Blind, Double-Dummy and Positive Control Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy and safety of Tongxiening Granules (, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea (IBS-D).@*METHODS@#A randomized, double-blind, double-dummy, and positive parallel controlled clinical trial was conducted from October 2014 to March 2016. Totally 342 patients from 13 clinical centers were enrolled and randomly assigned (at the ratio of 1:1) to a treatment group (171 cases) and a control group (171 cases) by a random coding table. The patients in the treatment group were administered orally with TXNG (5 g per time) combined with pinaverium bromide Tablet simulator (50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator (5 g per time) combined with pinaverium bromide Tablets (50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief (AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire (IBS-QOL), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and the recurrence rate at follow-ups. Safety indices including the adverse events (AEs) and related laboratory tests were evaluated.@*RESULTS@#Primary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set (FAS) and per protocol set (PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group (147/171,86.0%) was higher than the control group (143/171, 83.6%) by FAS (P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups (P>0.05). The recurrence rate at 8-week follow-up was 12.35% (10/18) in treatment group and 15.79% (12/76) in control group, respectively (P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups (P>0.05).@*CONCLUSION@#Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide. (No. ChiCTR-IPR-15006415).

Post-marketing evaluation of Fuganlin Oral Liquid in treatment of acute upper respiratory infection / 中草药

Objective: To evaluate the clinical efficacy and safety of Fuganlin Oral Liquid in treatment of acute upper respiatory infection (AURI) in pratical application. Methods: A multi-centered observational study was conducted. Total 2124 patients were administrated with Fuganlin Oral Liquid for one week, and observed the cure rate and the occurrence rate of complications in different levels, and the safety was evaluated. Results: The total cure rate was 95.12%, and there was no significant difference on it among different dosage and diagnosis groups, while patients (younger than one year old) took Fuganlin Oral Liquid alone had higher cure rate. The occurrence rate of complications was 0.24%, and there was no statistical difference among different dosage, age, and diagnosis groups, while patient took Fuganlin Oral Liquid alone had lower rate than combination therapy. The rateS of adverse events and adverse reaction were 1.37% and 1.04%, there was statistical difference except in different dosage groups. Conclusion: Fuganlin Oral Liquid has high cure rate and low complication rate. It has a good clinical efficacy, especially in young age groups. The efficacy of Qi deficiency group and wind heat syndrome group, even the disease diagnosis group was similar. A few clinical adverse events and adverse reaction was founded, high dosage group was as safe as the low dosage group. Above all, Fuganlin Oral Liquid has widely applied prospect in clinical practice.

Research methods for bioequivalence and its application in Chinese materia medica preparation products / 中草药

Bioequivalence has an important role in the new drug research, development of non-patent medicine, and post-marketing evaluation of drugs and is an essential step in the standardization and modernization of Chinese materia medica (CMM). With the acceleration of modernization of CMM, CMM preparation products made by different manufacturers differ in quality, resulting in different effects. Therefore, it is very important to strengthen the application of bioequivalent study in CMM preparation products to ensure the effectiveness and safety. In this paper, the research methods of the biological equivalence were introduced systematically, and the significance of the "component structure theory" to the study on biological equivalent of the CMM preparations has been elaborated, in order to improve the evaluation system of the biological equivalent for CMM preparations.