OBJECTIVE To analyze the development history， current status， and major challenges of central （cloud） pharmacies within China’s close-knit county-level medical communities， and to provide references for improving the overall effectiveness of the primary-level pharmaceutical supply and support system.METHODS Policy documents and practical case data related to central （cloud） pharmacies in county-level medical communities from 31 provinces （autonomous regions and municipalities） in China were collected. A qualitative approach combining policy text analysis and comparative case analysis was employed to longitudinally trace and cross-sectionally compare the development history and current status of central （cloud） pharmacies， identify existing problems， and propose targeted recommendations. RESULTS &CONCLUSIONS The development of central （cloud） pharmacies in China has undergone three stages： initial exploration， pilot expansion and mechanism deepening， and high-level promotion with local responses. While adhering to national policy directives， various regions have conducted diverse explorations in organizational and legal forms， management models， and institutional frameworks. However， several challenges remain， including insufficient policy guidance， an imperfect mechanism for drug coordination and supply security， weaknesses in hardware infrastructure and information technology development， and the need to strengthen statistical monitoring and outcome evaluation systems. It is recommended that the construction of central （cloud） pharmacies should be oriented toward achieving their fundamental functions， improve the institutional framework， adopt differentiated construction models tailored to local conditions， enhance the coordinated drug supply and support system， strengthen information technology infrastructure and professional capacity building， unify evaluation standards， and improve performance assessment mechanisms， so as to elevate the overall effectiveness of the primary-level pharmaceutical supply and support system.

OBJECTIVE To evaluate the cost-utility of iguratimod combined with methotrexate in the treatment of patients with active rheumatoid arthritis （RA） who failed monotherapy with conventional synthetic disease-modifying antirheumatic drugs （csDMARDs）.METHODS A cost-utility analysis was performed. A Markov model was constructed from the perspective of China’s healthcare system with a cycle length of 6 months to simulate the costs and health outcomes [quality-adjusted life years （QALYs）] of iguratimod combined with methotrexate versus different combined csDMARDs regimens over a 30-year time horizon. Efficacy and safety data were synthesized from randomized controlled trials via network meta-analysis. Cost parameters were derived from the Menet Database， published literature and other sources. The discount rate was set at 4.5%， and the willingness-to-pay （WTP） threshold was twice China’s per capita gross domestic product in 2025 （199 330.00 yuan/QALY）. One-way sensitivity analysis， probabilistic sensitivity analysis and scenario analysis were conducted to verify the robustness of the results.RESULTS Compared with methotrexate+sulfasalazine and sulfasalazine+leflunomide， iguratimod+methotrexate was a dominant regimen. Compared with methotrexate+leflunomide， the incremental cost-effectiveness ratio of iguratimod+methotrexate was 60 577.10 yuan/QALY， which was lower than the WTP threshold. Sensitivity analyses and scenario analysis confirmed favorable robustness of the above findings.CONCLUSIONS From the perspective of China’s healthcare system， iguratimod+methotrexate is cost-effective for active RA patients failing csDMARD monotherapy， in comparison with methotrexate+leflunomide， methotrexate+sulfasalazine and sulfasalazine+leflunomide regimens.

A 75-year-old female patient with postoperative colon cancer received fruquintinib (5 mg once daily, 3 weeks on and 1 week off per 4-week cycle). The patient had normal blood pressure in the past, and approximately one week after medication, she developed hypertension with systolic blood pressure 180-190 mmHg and unknown diastolic pressure. The patient′s blood pressure was with adequate control after self-administration of nifedipine sustained-release tablets twice (20 mg/dose). After 3 weeks of fruquintinib treatment, bilateral lower limb edema occurred in the patient, leading to a 1-week drug discontinuation. Upon resuming the medication for 1 day, the patient suddenly developed dyspnea and loss of consciousness. Chest CT revealed signs of heart failure. Laboratory tests showed high-sensitivity cardiac troponin I (hs-cTnI) 0.27 μg/L, creatine kinase (CK)-MB 7.13 μg/L, myoglobin 132.88 μg/L, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) 4 039.8 ng/L. Fruquintinib was discontinued, and the patient received myocardial nutritional support, diuretics, anticoagulants, hepatoprotective agents, and potassium supplementation, etc. On day 2, the patient regained consciousness with hs-cTnI 0.28 μg/L, CK-MB 4.63 μg/L, myoglobin 34.25 μg/L, and NT-proBNP 10 181.3 ng/L. Antiplatelet therapy, diuretics, lipid-lowering agents, and antihypertensive treatment were initiated. On day 3, color doppler echocardiography confirmed myocardial infarction complicated by heart failure. Fruquintinib-induced acute non-ST-segment elevation myocardial infarction with acute heart failure was considered. On day 6 of fruquintinib discontinuation, NT-proBNP decreased to 295.8 ng/L, and all laboratory test parameters normalized on day 9. One month later, repeated tests showed no abnormalities in the myocardial enzyme.

To provide auxiliary decision-making support to improve incentive policies for pediatric drug development and approval, we systematically review the current status of research on and approval of anti-epileptic drugs (AEDs) for children at home and abroad, and comprehensively analyze the existing barriers in China’s pediatric AED development and market approval process. Findings reveal that China lags behind some countries and regions included in this comparative study (United State of America, European Union, Japan and Australia, etc.) in terms of research and development (R&D) capability and progress in pediatric AEDs, with significant disparity in the diversity of approved drugs, formulations, and dosage forms. It is recommended that China enhance its policy support for R&D, optimize the drug evaluation and approval system, strengthen the management of drug allocation and utilization, promote rational drug use, reinforce post-marketing incentive policies and help foster a more favorable policy environment for the development and approval of pediatric medications.

A 75-year-old female patient with postoperative colon cancer received fruquintinib (5 mg once daily, 3 weeks on and 1 week off per 4-week cycle). The patient had normal blood pressure in the past, and approximately one week after medication, she developed hypertension with systolic blood pressure 180-190 mmHg and unknown diastolic pressure. The patient′s blood pressure was with adequate control after self-administration of nifedipine sustained-release tablets twice (20 mg/dose). After 3 weeks of fruquintinib treatment, bilateral lower limb edema occurred in the patient, leading to a 1-week drug discontinuation. Upon resuming the medication for 1 day, the patient suddenly developed dyspnea and loss of consciousness. Chest CT revealed signs of heart failure. Laboratory tests showed high-sensitivity cardiac troponin I (hs-cTnI) 0.27 μg/L, creatine kinase (CK)-MB 7.13 μg/L, myoglobin 132.88 μg/L, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) 4 039.8 ng/L. Fruquintinib was discontinued, and the patient received myocardial nutritional support, diuretics, anticoagulants, hepatoprotective agents, and potassium supplementation, etc. On day 2, the patient regained consciousness with hs-cTnI 0.28 μg/L, CK-MB 4.63 μg/L, myoglobin 34.25 μg/L, and NT-proBNP 10 181.3 ng/L. Antiplatelet therapy, diuretics, lipid-lowering agents, and antihypertensive treatment were initiated. On day 3, color doppler echocardiography confirmed myocardial infarction complicated by heart failure. Fruquintinib-induced acute non-ST-segment elevation myocardial infarction with acute heart failure was considered. On day 6 of fruquintinib discontinuation, NT-proBNP decreased to 295.8 ng/L, and all laboratory test parameters normalized on day 9. One month later, repeated tests showed no abnormalities in the myocardial enzyme.

In order to ensure the safety and efficacy of generic drugs for the substitution of narrow therapeutic index(NTI)drugs,and to improve and optimize China's generic drug substitution policy,we searched foreign literature databases and government websites to collect and sort out the typical measures taken by some foreign countries to ensure the safety and efficacy of generic drugs for the substitution of NTI drugs,including R&D registration,generic drug substitution and post-market surveillance.On the basis of comparative analysis,this paper summarizes the practices China can learn from.It can be seen that there are problems and challenges in China's generic drug substitution for NTI drugs,such as unclear targets for bioequivalence studies of NTI drugs,insufficient rational decision-making basis for generic substitution of NTI drugs,and imperfect post-market surveillance system,etc.It is recommended that we should formulate a list of NTI drugs,play the roles of physicians and pharmacists in generic drug substitution,adjust the generic drug substitution for NTI drugs according to the level of risk of drug use,and improve the reporting system for adverse reactions due to generic drug substitution.

OBJECTIVE To provide reference for the application of patient preference information in China by studying the application of patient preference information in the premarketing decision-making of medical products in the United States. METHODS The literature research method was used to explore the general situation， legal basis， and participants of the collection and application of patient preference information in the United States， analyze the application of patient preference information in premarketing decision-making of medical products in detail， and analyze the application status and challenges of patient preference information in China， so as to put forward suggestions. RESULTS & CONCLUSIONS United States has promoted the collection and application of patient preference information through several patient participation projects and legislation. The patient preference information is used to support premarketing decision-making of medical products： providing information for medical product development and design， and assisting clinical trial design in the research and development process； helping to support FDA’s marketing approval decisions， identifying patient groups whose benefits outweigh risks， and included in medical product descriptions in the marketing approval process. The application of patient preference information in China lacks the guidance of higher-level legal documents， and there are no targeted guidance documents. It is suggested that China should learn from the experience of the United States and clearly encourage the research and application of patient preference in higher-level legal documents； develop specific guidance documents for the collection and application of patient preference information； determine the weight and form of patient preference information to be considered in regulatory decision-making according to national conditions.

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.

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.

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.