Study on hospital exemption clause of advanced therapy medicinal products in EU and its enlightenment to China / 中国药房

OBJECTIVE To study the hospital exemption clause of advanced therapy medicinal products in the EU， and to provide policy recommendations for improving the regulatory system of cell and gene therapy （CGT） products in China. METHODS Through literature review and investigation of the official websites of EU member states， this study compared the differences in the application and implementation of the hospital exemption clause among member states from the perspectives of “non-conventional” definition， manufacturing standards， and pharmacovigilance requirements； the potential issues of hospital exemption clauses in practice were analyzed to propose policy recommendations based on the regulatory status of CGT in China. RESULTS & CONCLUSIONS EU has provided patients with rare diseases， who lack effective treatment or better therapy plans， with the opportunity to obtain new treatments through the hospital exemption clause， which has effectively improved the accessibility of medicines for patients. However， there still are certain disparities in the provisions of hospital exemption clause among EU member states. For instance， some member states have not explicitly defined “unconventional” circumstances； each member state has different requirements regarding production quality standards and pharmacovigilance requirement. Additionally， in the practical implementation of hospital exemption clause， issues such as poor transparency of information and a lack of certain restrictive conditions persist. Therefore， considering the current landscape and regulation of China’s CGT， it is recommended that China explore the clinical translational application of low-risk CGT in “unconventional” situations， strengthen the management of clinical translational application in terms of production quality standards and pharmacovigilance requirement. At the same time， it is necessary to further standardize the investigator initiated trials， and pay attention to the balance between clinical application and drug registration and marketing， thereby guiding the sustained and healthy development of China’s CGT.

Study on hospital exemption clause of advanced therapy medicinal products in EU and its enlightenment to China / 中国药房

OBJECTIVE To study the hospital exemption clause of advanced therapy medicinal products in the EU， and to provide policy recommendations for improving the regulatory system of cell and gene therapy （CGT） products in China. METHODS Through literature review and investigation of the official websites of EU member states， this study compared the differences in the application and implementation of the hospital exemption clause among member states from the perspectives of “non-conventional” definition， manufacturing standards， and pharmacovigilance requirements； the potential issues of hospital exemption clauses in practice were analyzed to propose policy recommendations based on the regulatory status of CGT in China. RESULTS & CONCLUSIONS EU has provided patients with rare diseases， who lack effective treatment or better therapy plans， with the opportunity to obtain new treatments through the hospital exemption clause， which has effectively improved the accessibility of medicines for patients. However， there still are certain disparities in the provisions of hospital exemption clause among EU member states. For instance， some member states have not explicitly defined “unconventional” circumstances； each member state has different requirements regarding production quality standards and pharmacovigilance requirement. Additionally， in the practical implementation of hospital exemption clause， issues such as poor transparency of information and a lack of certain restrictive conditions persist. Therefore， considering the current landscape and regulation of China’s CGT， it is recommended that China explore the clinical translational application of low-risk CGT in “unconventional” situations， strengthen the management of clinical translational application in terms of production quality standards and pharmacovigilance requirement. At the same time， it is necessary to further standardize the investigator initiated trials， and pay attention to the balance between clinical application and drug registration and marketing， thereby guiding the sustained and healthy development of China’s CGT.

Analysis on the Pricing and Reimbursement Strategy of Orphan Drugs in Typical European Countries and Its Enlighten-ment to China / 中国卫生经济

The pricing and reimbursement of orphan drugs are related to the accessibility of patients,and are of great significance to the prevention and guarantee of rare diseases.European countries have formed special standards and paths for health technology evaluation,and established special payment funds and diversified risk-sharing agreements,which have effectively improved the accessibility of orphan drugs.Based on this,it selected typical European countries to compare the orphan drug pricing and reimbursement methods.Then,it put forward some suggestions"building orphan drug health technology evaluation accelerated program,exploring the health of orphan drug classification security mechanism,and attaining supply incentives and development incentives through orphan drug pricing and adjustment",to optimize the basis for the orphan drug market access mechanism to provide reference.

Analysis of constraints and policy recommendations for the development of pediatric drugs in China:Based on the perspective of pharmaceutical enterprises / 中国卫生政策研究

Objective:To provide a basis for improving the design and implementation of policies for ensuring the supply of pediatric drugs in China.Method:Based on the perspective of pharmaceutical enterprises,reviewed literature and conducts questionnaire surveys to identify the constraints in the development of pediatrict drugs throughout the entire drug lifecycle,and analyzes the constraints'concentration and urgency.Result:The main constraints include:difficulty in conducting clinical trials for children;the current registration and approval rules lack consideration for the specificity of pediatric drugs and specific requirements for application materials;lack of implementation rules and measures in the implementation process of incentive policies for pediatric drug production;The market interest mechanism of pediatric drugs is not yet perfect.Among them,research and development and payment for use are currently relatively concentrated issues.Discussion and suggestions:It is recommended that China fully utilize existing clinical trial data of pediatric and broaden sources,take multiple measures to increase investment in pediatric drug R&D;Develop special guidelines for pediatric drug application and encourage adult drug registration to submit pediatric research plans;Explore the optimization path of pediatrict drug production and supply based on typical cases;Provide more space for pediatric drugs in the rules of drug use and payment.

Mycoplasma infection of cancer cells enhances anti-tumor effect of oxidized methylcytidines.

Oxidized methylcytidines 5-hydroxymethyl-2'deoxycytidine (5hmdC) and 5-formy-2'deoxycytidine (5fdC) are deaminated by cytidine deaminase (CDA) into genome-toxic variants of uridine, triggering DNA damage and cell death. These compounds are promising chemotherapeutic agents for cancer cells that are resistant to pyrimidine derivative drugs, such as decitabine and cytarabine, which are inactivated by CDA. In our study, we found that cancer cells infected with mycoplasma exhibited a markedly increased sensitivity to 5hmdC and 5fdC, which was independent of CDA expression of cancer cells. In vitro biochemical assay showed that the homologous CDA protein from mycoplasma was capable of deaminating 5hmdC and 5fdC into their uridine form. Moreover, mycoplasma infection increased the sensitivity of cancer cells to 5hmdC and 5fdC, whereas administration of Tetrahydrouridine (THU) attenuated this effect, suggesting that mycoplasma CDA confers a similar effect as human CDA. As mycoplasma infection occurs in many primary tumors, our findings suggest that intratumoral microbes could enhance the tumor-killing effect and expand the utility of oxidized methylcytidines in cancer treatment.

Participation of pharmacists and patients in web-based pharmaceutical care consultation based on MEDICODE.

BACKGROUND: The participation of providers and patients in medical communication is the core element of shared decision making. Furthermore, web-based pharmaceutical care consultation is increasingly necessary, welcomed and popular. OBJECTIVE: This study aimed to analyze the participation of pharmacists and patients in web-based pharmaceutical care consultation, so as to form the promotion strategy for both parties' participation. METHODS: Data of pharmacist-patient encounters was obtained from the online platform 'Good Doctor Website' from March 31, 2012 to June 22, 2019. MEDICODE was employed to analyze the participation of pharmacists and patients in web-based pharmaceutical care consultation using dialogue ratio, the preponderance of initiative, and dialogical roles (information provider, listener, instigator and participant). RESULTS: This study included 121 pharmacist-patient encounters which discussed 382 specifically named medications. On average, 3.75 specific themes were discussed per medication. Among the 29 specific themes observed, 16 were initiated primarily by patients and 13 by pharmacists, 22 were primarily monologue, 6 were primarily dialogue, and 1 was a combination of the two. Pharmacists and patients were information providers or listeners in most content theme categories, such as possible main effect, possible adverse effect, instructions, warnings, adherence, designation, and observed adverse effect. CONCLUSIONS: Pharmacists and patients exchanged less drug-related information in web-based pharmaceutical care consultation. The exchange had more patient-dominated behaviors and more of a monologue. Furthermore, pharmacists and patients were mainly information providers or listeners in communication. The participation of both parties was insufficient.

Introduction of Australian post-market reviews of pharmaceutical benefits scheme subsidized medicines and its implication to China / 中国药房

OBJECTIVE To provide a reference for strengthening the post-admission management of drugs on the medicare formulary in China. METHODS The basic situation， implementation process and effect of post-market reviews （PMR） were introduced after marketing approval of the Australian pharmaceutical benefits scheme （PBS） subsidized medicines. The suggestions were put forward for post-admission management of medicare formulary drugs in China. RESULTS & CONCLUSIONS PMR system exemplified Australia’s concept of life-cycle management of medicines on the PBS catalogue； as a mechanism for managing the admission and adjustment of PBS medicines， it provided a continuous evaluation of medicines in the PBS catalogue； the process mainly included two types： the pre-initiation process of PBS drug review and the PBS drug review process， involving steps such as drug selection， determination of review scope， and implementation management. Through PMR， Australia had completed the review of multiple medicines in nine treatment areas including diabetes， childhood asthma and Alzheimer’s disease in the PBS catalogue. The author suggests that China can improve the post-admission review of medicines at the institutional level （clarifying the selection criteria and methods of the review object， main procedures and responsible parties， and ensuring the transparency of the review process）； specify the National Healthcare Security Administration or the third-party organization until a special technical organization is established to take charge of this work； at the same time， further improve the construction of data collection and monitoring systems.

Introduction and enlightenment of foreign remote inspection mode of pharmaceutical production / 中国药房

OBJECTIVE To provide reference for the construction of remote inspection mode of pharmaceutical production in China. METHODS By combing the guidance documents of remote inspection and related pilots issued abroad， the experience of constructing remote inspection mode of pharmaceutical production was summarized. RESULTS & CONCLUSIONS Typical foreign countries and regions have carried out remote inspection pilots all over the world， and clearly defined the application situation， implementation process， inspection techniques and related points for attention of remote inspection of pharmaceutical production. In terms of application， the European Union pointed out four specific applicable situations， including travel restrictions， while the United States stipulated that remote inspection was applicable to pre-approved inspection and so on. In terms of the implementation process， the United States developed a four-step method of remote inspection， while the European Union has defined the specific implementation process of remote inspection in more detail. In comparison， Japan paid more attention to the remote inspection process of production documents. In terms of inspection techniques， the European Union used 360° cameras， Matterport 3D technology and document review software to realize the remote inspection of production sites and production documents. In terms of attention points for remote inspection， the United States required that access rights should be set for information sharing to avoid information disclosure. Both the European Union and the United States required inspectors to be trained and equipment inspected before remote inspection. It is suggested that China should formulate unified guidelines for remote inspection of pharmaceutical production， clarify the applicable situations， and formulate the implementation process of remote inspection of pharmaceutical production with reference to the opinions of drug manufacturers. In addition， intelligent remote inspection technology can be used in combination with the information construction level of drug manufacturers， and remote inspection training program can be formulated to cultivate professional remote inspection team.

Isoliquiritigenin induces HMOX1 and GPX4-mediated ferroptosis in gallbladder cancer cells / 中华医学杂志(英文版)

BACKGROUND@#Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated.@*METHODS@#The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry.@*RESULTS@#ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 .@*CONCLUSION@#ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC.

Experience and enlightenment of generic drug substitution promotion policy in drug use in typical foreign countries / 中国卫生政策研究

Objective:From the link of drug use to improve China's generic drug substitution promotion policy to provide suggestions.Methods:Literature research method was used to explore the ideas and typical measures of promoting generic drug substitution in Europe,the United States,Japan and other countries.Combined with the existing problems in the process of generic drug substitution in China,specific suggestions were put forward to improve the promotion policy of generic drug substitution in the process of drug use in China.Results and conclusions:Through the experience research of Europe,the United States,Japan and other countries,it is found that typical countries outside the region have formed the idea of"accepting generic drugs-scientific and reasonable substitution-continuous feedback and improvement"in the process of promoting generic drug substitution.It is suggested that China incorporate the opinions of doctors and patients into the generic drug substitution decision-making,establish generic drug substitution rules based on risk,strengthen the real-world data research and monitoring and evaluation of generic drug substitution,strengthen the disclosure of generic drug information and policy publicity,further improve the promotion policy of generic drug substitution in the drug use process in China,and promote the alternative use of generic drugs.

Research on the supply guarantee system of orphan drugs in South Korea from the perspective of accessibility and its enlightenment / 中国药房

OBJECTIVE To systematically introduce the supply guarantee system of orphan drugs in South Korea， and to provide reference for improving the accessibility of orphan drugs in China. METHODS The basic characteristics and practical experience of supply guarantee system of orphan drugs in South Korea were summarized by studying the marketing incentive mechanism， reserve supply mechanism and emergency use mechanism. Then， based on the research on the current situation and existing problems of orphan drug supply in China， specific suggestions were put forward to improve the accessibility of orphan drugs in China. RESULTS & CONCLUSIONS South Korea has effectively improved the accessibility of orphan drugs through orphan drug identification channels and supporting incentive policies， relying on the reserve supply mechanism and the import route for emergency use. Therefore， it is suggested that China should guarantee the normal supply of orphan drugs from three aspects： improving the recognition and incentive policy of orphan drugs， building a full-time management department of orphan drugs， and optimizing the temporary import path.

Framework design of WHO and typical national essential medicine lists and its implications for China / 中国药房

OBJECTIVE To sort out the common presentation forms and components of the framework of domestic and foreign essential medicine lists （EMLs）， in order to provide reference for optimizing the framework of the Chinese EML. METHODS The latest edition of the EMLs of WHO， China， South Africa， India， Malaysia and other typical countries were compared， and the similarities and differences of the presentation form and constituent elements of the list framework were analyzed. RESULTS & CONCLUSIONS The common presentation forms of WHO and typical countries’ EMLs included version， classifications and symbols， of which management ideas， functions， and implementation difficulties varied； common framework elements included target population， hospital levels， drug use conditions， core and supplementary lists and procurement priority. Through comparison， it was found that the information covered by the Chinese EML was relatively thin， and the framework design had not yet fully played the ideal role in guiding clinical rational drug use and optimizing the allocation of health resources， and there was still some room for improvement. It is recommended that China clarify the characteristics and roles of different presentation forms of the EML， and reasonably set the EML framework based on national conditions and development needs； the multi-dimensional drug information should be supplemented， such as clinical use， economy， and policy attributes of drugs in the EML， to ensure the rational use of essential drugs； it is also necessary to add “the level of hospitals” in the framework of the EML， refine the management requirements for the allocation and use of essential medicine， and optimize the resource allocation of hospitals.

Cultivable endophytic fungal community associated with the karst endemic plant Nervilia fordii and their antimicrobial activity.

Endophytic fungi from medicinal plants with specific pharmacological functions attract much attention to provide the possibility of discovering valuable natural drugs with novel structures and biological activities. Nervilia fordii is a rare and endangered karst endemic plant that is used as medicine and food homology in Guangxi, China. These plants have been reported to have antimicrobial, antitumor, antiviral, and anti-inflammatory activities. However, few studies have focused on the diversity and antibacterial activity of endophytic fungi from N. fordii. In the present study, 184 endophytic fungi were isolated from the healthy tissues of N. fordii, and their molecular diversity and antimicrobial activities were analyzed for the first time. These fungi were categorized into 85 different morphotypes based on the morphological characteristics and the similarity between the target sequence and the reference sequence in the GenBank database. With the exception of 18 unidentified fungi, the fungal isolates belonged to at least 2 phyla, 4 classes, 15 orders, 45 known genera, and 45 different species, which showed high abundance, rich diversity, and obvious tissue specificity. All isolates were employed to screen for their antimicrobial activities via the agar diffusion method against Escherichia coli, Staphylococcus aureus, and Candida tropicalis. Among these endophytes, eight strains (9.41%) displayed inhibitory activity against E. coli, 11 strains (12.94%) against S. aureus, and two strains (2.35%) against C. tropicalis, to some extent. In particular, our study showed for the first time that the fungal agar plugs of Penicillium macrosclerotiorum 1151# exhibited promising antibacterial activity against E. coli and S. aureus. Moreover, the ethyl acetate (EA) extract of P. macrosclerotiorum 1151# had antibacterial effects against E. coli and S. aureus with a minimum inhibitory concentration (MIC) of 0.5 mg ml-1. Further research also confirmed that one of the antimicrobial compounds of P. macrosclerotiorum 1151# was methyl chloroacetate and exhibited excellent antibacterial activity against E. coli and S. aureus up to 1.71-fold and 1.13-fold compared with tetracycline (TET) (5 mg ml-1), respectively. Taken together, the present data suggest that various endophytic fungi of N. fordii could be exploited as sources of novel natural antimicrobial agents.

Effect of Mirena intrauterine device combined with GNRH-A on endometriosis, sex hormone level and carbohydrate antigen 125.

To investigate the clinical value of Mirena (levonorgestrel intrauterine sustained release system) combined with gonadotropin-releasing hormone agonist (GnRH-a) in patients with endometriosis, 80 patients with endometriosis (March 2019 ~ March 2020) were selected as the research object. According to the "random number table method", they were divided into the control group (treated with GnRH-a) and the observation group (treated with Mirena IUD combined with GnRH-a), with 40 cases included in each group. The total clinical efficacy, sex hormone level, carbohydrate antigen 125 (CA125) level, degree of pain and recurrence rate indexes were compared between the two groups. Results showed that the total effective rate of 92.50% in the observation group was higher than 75.00% in the control group (P < 0.05). Intercourse pain of dysmenorrhea and sexual intercourse pain (VAS) in the two groups were compared before treatment. After treatment, the VAS scores in the two groups decreased, and the VAS scores in the observation group were lower than those in the control group (P<0.05). The levels of E2, FSH, LH and CA125 in the observation group were lower than in the control group (P<0.05). The recurrence rate of 5.00% in the observation group was lower than 20.00% in the control group (P<0.05). In conclusion, Mirena IUD combined with GnRH-a can improve the clinical efficacy of endometriosis, improve ovarian function, effectively regulate serum factors, further alleviate the symptoms of sexual intercourse pain and dysmenorrhea, control the risk of postoperative recurrence and achieve an ideal therapeutic effect.

Effect of Implantation and Fixation of Mirena in the Treatment of Adenomyosis and its Influence on Serum Inflammatory Factors.

This experiment was carried out to analyze the placement and fixation of Mirena in the treatment of adenomyosis (AM) and its influence on the level of serum inflammatory factors in patients. For this purpose, the subjects of this study were 100 AM patients hospitalized in our hospital from June 2019 to June 2021. They were divided into two groups according to the lottery method (n=50 for each group). The control group was treated with intramuscular triptorelin after the operation, and the observation group was treated with Mirena during the operation. Sex hormone indexes, VAS score, uterine volume, serum inflammatory indexes, the total incidence of adverse reactions, WHOQOL-BREF score and recurrence rate were compared between the two groups. Results showed that in the observation group after treatment E2VAS score and uterine volume were lower, serum IL-8 and TNF-A were lower, the whoqOL-BREf score was higher, and the recurrence rate (0) was lower than that in the control group (12.00%). The total incidence of adr in the observation group (4.00%) was lower than in the control group (8.00%). Then intraoperative placement of Mirena can effectively regulate sex hormone indexes of AM patients, reduce uterine volume, relieve dysmenorrhea symptoms, reduce the inflammatory response, improve quality of life, and reduce recurrence rate, without obvious adverse reactions.

Review of international experience about the adjustment procedure of essential medicine list / 中国药房

In order to further consolidate the national essential medicine system and establish and improve the selection and adjustment mechanism of the national essential medicine list ，the Department of Drug Policy and Essential Medicine of the National Health Commission of the People ’s Republic of China recently has issued the Measures for the Administration of the National Essential Medicine List （Revised Draft ）. Under the background that China is in a critical period of improving the management procedures for the adjustment of the essential medicines list ，how to better design the adjustment procedure ，clarify the operation process and material requirements of each link ，ensure social participation and improve work transparency are important problems to be solved. By consulting the official websites of World Health Organization （WHO）and some typical countries with essential medicine system as well as related foreign literature ，the advanced practices of WHO and some typical countries in the adjustment procedures of the essential medicine list were summarized from 6 stages，such as start-up stage ，the material collection and summary stage ，the evaluation stage ，result publicity stage ，relief stage and application and promotion stage. It is suggested that China can learn from the relevant successful international experience ，scientifically set the adjustment cycle ，establish a normalized feedback mechanism with multi-agent participation ，design a standardized material collection process and a scientific and efficient evaluation process ，and improve the transparency and social identity of the publicity of the selection results of essential medicines ， so as to build a more scientific and perfect adjustment procedure of essential medicine list.

CHINA PH ARMACY Volume 33，Number 4，February 28，2022 Semimonthly Table of Contents Empirical study on the influential factors of the drug complaint and reportin g system in China / 中国药房

OBJECTIVE To improve the drug complaint and reporting system in China ，and to provide reference for improving the social multi-component governance level of the drug safety. METHODS Taking Guangdong province as an example ， literature review ，questionnaire survey ，structural equation model and other methods were used to analyze influential factors of the drug complaint and reporting system ，such as “Internet+”approach，drug quality ，specialized drug knowledge ，complaint and reporting procedures ，complaint and reporting methods ，complaint and reporting motivation ，governmental reward ，administrative review or litigation. RESULTS & CONCLUSIONS A total of 3 375 questionnaires were received ，all of which were valid ；the vast majority of respondents lived in Guangdong province. The results of the empirical analysis of the influential factors of drug complaint and reporting system showed that the path coefficients of “Internet + ”approach and specialized drug knowledge ， complaint and reporting procedures ，complaint and reporting methods were all greater than 0.9，indicating“Internet+”promoted the transformation of the way and behavior of complaint and reporting. It is suggested that the design of the drug complaint and reporting system should not only attract the public to participate in drug complaint and reporting ，but also cultivate the public ’s management capacity through the approach of internet ， standardize professional anti-counterfeiting behavior ， promote the institutional reform of “digital government ”，and appropriately adjust the work responsibilities of drug regulatory department ，so as to reduce the number of drug complaint and reporting in China ，and optimize the drug safety governance system.

Comparative study on the management and implementation of continuing education for licensed pharmacists in 31 provinces of China / 中国药房

OBJECTIVE To provide reference for improving the continuing education management for licensed pharmacists in China. METHODS By searching related policies ，notices and documents of continuing education of licensed pharmacists in various provinces in China ，the retrieval time limit was from the implementation of the licensed pharmacist qualification access system in 1994 to December 31，2021. The organizational structure ，implementation status and problems of continuing education management for licensed pharmacists in 31 provinces were analyzed to put forward the suggestions. RESULTS & CONCLUSIONS At present ， the management subjects of continuing education for licensed pharmacists in China at the national level are still unclear ，and the management subjects of continuing education at the local level are mostly provincial drug administration and （licensed）pharmacist association，and some are pharmaceutical societies ，so the management system needs to be straightened out. At present ，most provinces have selected teaching institutions through public bidding ，basically realize the separation of discipline ，but the openness and transparency of selection standards need to be strengthened. In addition ，there are still some problems ，such as teaching content and methods need to be enriched and optimized ，and insufficient funds guarantee in most areas. It is suggested to clarify the division of responsibilities for the continuing education management of licensed pharmacists in China ，improve the management of teaching institutions ，enrich the teaching contents and forms of continuing education of licensed pharmacists ，and ensure the management funds of continuing education of licensed pharmacists.

CHINA PH ARMACY Volume 33，Number 16，August 30，2022 Semimonthly Table of Contents Analysis of trans-provincia l distribution supervisio n of TCM decoction pieces in accordance with provincial standards from the perspective of benefit and risk / 中国药房

OBJECTIVE To provide ideas for solving the dispute of trans-provincial distribution of traditional Chinese medicine （TCM） decoction pieces in accordance with provincial standards （hereinafter referred to as “local TCM decoction pieces”）. METHODS Through simulation scenarios and collecting actual cases ，the conditions of trans-provincial distribution of local TCM decoction pieces were listed ；the official websites were searched or relevant personnel of drug supervision were interviewed；the current situation of trans-provincial distribution supervision of local TCM decoction pieces in China were sorted out. Based on the stakeholder theory ，the benefits and risks of main stakeholders were discussed to put forward relevant suggestions from the perspective of benefit /risk balance. RESULTS & CONCLUSIONS The conditions of trans-provincial distribution of local TCM decoction pieces in China included enterprises in B province produced TCM decoction pieces according to the A provincial standards，sold and used them in A province ；enterprises in B province produced TCM decoction pieces according to the B provincial standards ，sold and used them in A province ；enterprises in B province produced TCM decoction pieces according to the C provincial standards ，sold and used them in A province. At present ，there are no clear relevant provisions of national laws about trans-provincial distribution supervision of local TCM decoction pieces. Local regulatory opinions mainly come from the reply of the official website of drug regulatory department to online consultation ，and only Shandong ，Shanghai，Liaoning and Jiangxi have issued replies or normative documents. Totally 41.9％，38.7％ and 32.3％ of the provinces respectively allow the trans-provincial distrbution of local TCM decoction pieces in the above 3 conditions；in addition ，32.3％，16.1％ and 22.6％ provinces have unclear regulatory attitudes towards the 3 conditions. The benefits and risks analysis of relevant stakeholders shows that it is more in line with the scientific regulatory concept of benefit/risk balance to conditionally allow trans-provincial distribution of local TCM decoction pieces ，but the regulatory effect depends on the scientificity of the regulatory strategy. It is suggested that the drug regulatory departments clarify the relationship between the national and local standards for TCM decoction pieces and dingrl375@163.com differentiate the varieties of collection ；clear the regulatory requirements for trans-provincial distribution of local TCM decoction pieces by issuing high-level legal d ocuments；enrich regulatory measures and means ，and gradually adjust the requirements of trans-provincial distribution of local TCM decoction pieces .

Economic evaluation of nivolumab combined with ipilimumab in the first-line treatment of unresectable malignant pleural mesothelioma / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of nivolumab combined with ipilimumab in the first-line treatment of unresectable malignant pleural mesothelioma （MPM）. METHODS From the perspective of healthcare system ，a partitioned survival model were developed ，the cost-effectiveness of nivolumab combined with ipilimumab （dual-immunotherapy plan ）versus chemotherapy in the first-line treatment of unresectable MPM by cost-utility analysis. Clinical trial data were collected from CheckMate 743 study. Direct medical cost included drug costs ，disease management cost and cost of treatment of adverse reactions. Costs and utilities were discounted at an annual rate of 5％. The willingness to pay threshold was 3 times of gross domestic product （GDP）per capita in 2021 [242 928 yuan/QALY（quality-adjusted life year ）]. Scenario analysis was used to analyze and compare the two regimens under the scenario of complimentary drug for patients in dual-immunotherapy group. The robustness of the findings was evaluated by one-way sensitivity analysis and probabilistic sensitivity analysis. RESULTS Baseline analysis results showed that total cost of dual-immunotherapy regimen was higher than that of chemotherapy regimen ，and the utility was also better than that of chemotherapy plan ；the incremental cost-effectiveness ratio （ICER）was 417 122.2 yuan/QALY，which was higher than the willingness to pay threshold ；the dual-immunotherapy regimen was not cost-effective compared to the chemotherapy regimen. Under the scenario of complimentary drug ，the cost of dual-immunotherapy was 327 454.5 yuan，ICER was 75 664.1 yuan/QALY，which was lower than the willingness to pay threshold and resulted in a reversal of the baseline analysis. One-way sensitivity analysis showed that under the health states of progression free survival and progressive disease ，utility value and the price of nivolumab had a greater impact on the ICER value. Probabilistic sensitivity analysis showed that the results of baseline analysis were robust. CONCLUSIONS At a 163.com willingness to pay threshold of 3 times of GDP per capita in nivolumab combined with ipilimumab is not cost-effective compared with chemotherapy regimen in the first-line treatment of unresectable MPM. However ，if patients receive complimentary drugs ，the dual-immunotherapy regimen is cost-effective.