OBJECTIVE To further standardize the technical operations and management processes throughout therapeutic drug monitoring （TDM）， clarify the clinical value of TDM implementation， improve the scientific validity and reliability of monitoring results， and provide a solid reference basis for the formulation and optimization of clinical individualized precision dosing regimens. METHODS The Guidelines for the Management of Therapeutic Drug Monitoring were formulated in accordance with the latest definition of guidelines by the Institute of Medicine of the National Academies and the standard guideline development methodology of the World Health Organization， and in compliance with the requirements of the appraisal of guidelines for research and evaluation. A modified Delphi method was adopted to establish the research question system； evidence-based medicine research methods were applied to systematically search multiple databases to screen the latest and most comprehensive evidence. Evidence was graded and evaluated based on the evidence grading system of the Chinese Evidence-Based Medicine Center， and the grading criteria for recommendation strength from the Oxford Centre for Evidence-Based Medicine were used to determine the recommendation strength. The recommendation opinions were formed through multidisciplinary expert consensus. RESULTS The Guidelines for the Management of Therapeutic Drug Monitoring cover four core modules， including TDM application indications， technical procedures， result interpretation and clinical application， and quality control， involving 18 primary research questions， 34 secondary research questions， and yield 82 recommendations. CONCLUSIONS The guidelines systematically standardize the key technical links and management requirements of the whole TDM process， provide scientific and operable standardized tools， help improve the standardization level of TDM work， promote the translation of monitoring results into clinical decision-making， and provide strong support for precision personalized medicine and ensuring the safety and rationality of medication use.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs， and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization （WHO）， strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States， and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions； research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center， and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions， including topic selection， evaluation implementation， evidence evaluation， and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs， which can effectively guide the high-quality and high-efficient development of this work， enhance the standardized output and transformation application value of evaluation evidence， and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.

OBJECTIVE To provide standardized guidance for the clinical application and management of biosimilars， and promote their widespread and rational use in clinical treatment. METHODS The design， planning， and drafting process as well as the full report of Evidence-based Guideline for the Management of Clinical Application of Biosimilars in China （2024 Edition） followed the WHO Handbook for Guideline Development （2nd edition）， which fully considered the best current evidence from evidence-based medicine， multidisciplinary expert experience， and patient preferences and values. Grading of Recommendations Assessment， Development， and Evaluation （GRADE） approach was adopted to evaluate the quality of evidence and determine the strength of recommendations. RESULTS & CONCLUSIONS Evidence-based Guideline for the Management of Clinical Application of Biosimilars in China （2024 Edition） presented 10 recommendations including 7 strong recommendations and 3 weak recommendations. The recommendations covered the entire process of clinical application and management of biosimilars. Medical institutions and relevant health regulatory departments can refer to this guideline for the scientific management of the extrapolation of unapproved indications of biosimilars. Healthcare providers can refer to this guideline for pre-treatment assessments， patient education， pre-treatment regimen before administration， and dosage regimen adjustments. Multidisciplinary medical teams can refer to this guideline to provide pharmacovigilance and patient management throughout the treatment process.

Objective:To explore the clinical characteristics of mirtazapine-related thrombocytopenia.Methods:The diagnosis and treatment of a patient with mirtazapine-related thrombocytopenia who was admitted to the Aerospace Center Hospital was reported, and the main clinical data (gender, age, indications of mirtazapine use, dosage of mirtazapine, combined medication, platelet count before and after medication, time from application of mirtazapine to thrombocytopenia occurrence, clinical treatment and prognosis, etc.) of the case and similar cases collected by searching relevant databases (up to August 31, 2023) were analyzed by descriptive statistic method.Results:A total of 9 patients were enrolled in the analysis, including 4 males and 5 females; the age ranged from 28 to 74 years, with a median age of 52 years. The indication of medication was depression in 8 patients, and 1 had no record. The daily dose of mirtazapine was 15 mg in 4 patients, 30 mg in 3 patients, and no record in 2 patients. Two patients were treated with mirtazapine alone, 6 patients were treated with mirtazapine combined with other drugs, and it was not recorded in 1 patient. The time from the application of mirtazapine to occurrence of thrombocytopenia in the 9 patients ranged from 2 to 28 days, with a median time of 8 days. The severity of thrombocytopenia was grade 1, 3, and 4 in 3, 3, and 2 patients, respectively; 1 patient had no relevant record. Of the 5 patients with severe thrombocytopenia, 3 developed bleeding, and 1 had skin ecchymosis. The results of drug-dependent antiplatelet antibody test in 2 patients were positive. Nine patients stopped mirtazapine treatment after diagnosis of thrombocytopenia, 6 patients did not receive special intervention, and 3 patients were given symptomatic treatments. After drug withdrawal for 2-43 days with the median time of 9 days, platelet counts returned to the reference range in 7 patients, platelet count increased in 1 patient, and platelet count was unknown but skin symptom was improved in 1 patient.Conclusions:Mirtazapine-related thrombocytopenia usually occurs within 10 days of treatments, which can be improved after drug withdrawal. It is suggested to monitor the blood routine before and after the application of mirtazapine.

Pre-marketing clinical trials may fail to detect rare or delayed adverse drug reactions (ADRs) due to insufficient sample size and short follow-up periods. Therefore, continuous post-marketing safety evaluation is necessary. Evidence generation relies on discovering ADR signals and conducting studies to verify specific risks. Integrating evidence from multiple sources through methods like meta-analysis can further enhance the comprehensiveness and reliability of drug safety evaluations. Additionally, risk management in clinical practice should be emphasized by developing standardized clinical guidelines and establishing decision support systems to facilitate the dissemination and application of evidence, ensuring its practical use. Constructing an evidence ecosystem not only helps identify and understand potential medication safety issues, but also enhance the scientific and practical aspects of risk management, ultimately reducing patient harm from ADRs.

Objective:To explore the clinical characteristics of mirtazapine-related thrombocytopenia.Methods:The diagnosis and treatment of a patient with mirtazapine-related thrombocytopenia who was admitted to the Aerospace Center Hospital was reported, and the main clinical data (gender, age, indications of mirtazapine use, dosage of mirtazapine, combined medication, platelet count before and after medication, time from application of mirtazapine to thrombocytopenia occurrence, clinical treatment and prognosis, etc.) of the case and similar cases collected by searching relevant databases (up to August 31, 2023) were analyzed by descriptive statistic method.Results:A total of 9 patients were enrolled in the analysis, including 4 males and 5 females; the age ranged from 28 to 74 years, with a median age of 52 years. The indication of medication was depression in 8 patients, and 1 had no record. The daily dose of mirtazapine was 15 mg in 4 patients, 30 mg in 3 patients, and no record in 2 patients. Two patients were treated with mirtazapine alone, 6 patients were treated with mirtazapine combined with other drugs, and it was not recorded in 1 patient. The time from the application of mirtazapine to occurrence of thrombocytopenia in the 9 patients ranged from 2 to 28 days, with a median time of 8 days. The severity of thrombocytopenia was grade 1, 3, and 4 in 3, 3, and 2 patients, respectively; 1 patient had no relevant record. Of the 5 patients with severe thrombocytopenia, 3 developed bleeding, and 1 had skin ecchymosis. The results of drug-dependent antiplatelet antibody test in 2 patients were positive. Nine patients stopped mirtazapine treatment after diagnosis of thrombocytopenia, 6 patients did not receive special intervention, and 3 patients were given symptomatic treatments. After drug withdrawal for 2-43 days with the median time of 9 days, platelet counts returned to the reference range in 7 patients, platelet count increased in 1 patient, and platelet count was unknown but skin symptom was improved in 1 patient.Conclusions:Mirtazapine-related thrombocytopenia usually occurs within 10 days of treatments, which can be improved after drug withdrawal. It is suggested to monitor the blood routine before and after the application of mirtazapine.

Pre-marketing clinical trials may fail to detect rare or delayed adverse drug reactions (ADRs) due to insufficient sample size and short follow-up periods. Therefore, continuous post-marketing safety evaluation is necessary. Evidence generation relies on discovering ADR signals and conducting studies to verify specific risks. Integrating evidence from multiple sources through methods like meta-analysis can further enhance the comprehensiveness and reliability of drug safety evaluations. Additionally, risk management in clinical practice should be emphasized by developing standardized clinical guidelines and establishing decision support systems to facilitate the dissemination and application of evidence, ensuring its practical use. Constructing an evidence ecosystem not only helps identify and understand potential medication safety issues, but also enhance the scientific and practical aspects of risk management, ultimately reducing patient harm from ADRs.

BACKGROUND: Clinical trial evidence is limited to identify better topical non-steroidal anti-inflammatory drugs (NSAIDs) for treating knee osteoarthritis (OA). We aimed to compare the clinical efficacy and safety of flurbiprofen cataplasms (FPC) with loxoprofen sodium cataplasms (LSC) in treating patients with knee OA. METHODS: This is an open-label, non-inferiority randomized controlled trial conducted at Peking University Shougang Hospital. Overall, 250 patients with knee OA admitted from October 2021 to April 2022 were randomly assigned to FPC and LSC treatment groups in a 1:1 ratio. Both medications were administered to patients for 28 days. The primary outcome was the change of pain measured by visual analog scale (VAS) score from baseline to day 28 (range, 0-10 points; higher score indicates worse pain; non-inferiority margin: 1 point; superiority margin: 0 point). There were four secondary outcomes, including the extent of pain relief, the change trends of VAS scores, joint function scores measured by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and adverse events. RESULTS: Among 250 randomized patients (One patient without complete baseline record in the flurbiprofen cataplasms was excluded; age, 62.8 ± 10.5 years; 61.4% [153/249] women), 234 (93.6%) finally completed the trial. In the intention-to-treat analysis, the decline of the VAS score for the 24-h most intense pain in the FPC group was non-inferior, and also superior to that in the LSC group (differences and 95% confidence interval, 0.414 (0.147-0.681); P <0.001 for non-inferiority; P = 0.001 for superiority). Similar results were observed of the VAS scores for the current pain and pain during exercise. WOMAC scores were also lower in the FPC group at week 4 (12.50 [8.00-22.50] vs . 16.00 [11.00-27.00], P = 0.010), mainly driven by the dimension of daily activity difficulty. In addition, the FPC group experienced a significantly lower incidence of adverse events (5.6% [7/124] vs . 33.6% [42/125], P <0.001), including irritation, rash and pain of the skin, and sticky hair uncovering pain. CONCLUSIONS This study suggested that FPC is superior to LSC for treating patients with knee OA in pain relief, joint function improvement, and safety profile.
Humans ; Female ; Middle Aged ; Aged ; Osteoarthritis, Knee/drug therapy* ; Flurbiprofen/therapeutic use* ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use* ; Pain/drug therapy* ; Treatment Outcome ; Double-Blind Method

Exposure to antineoplastics is a potential health threat. If improperly disposed, it will also cause environmental pollution, which is a medical safety issue worthy of attention. In order to improve the protection awareness of healthcare professionals exposed to antineoplastic drugs (medical personnels, drug transportation staffs, patients and their caregivers, etc.), standardize exposure protection operations, and reduce the risk and harm of occupational exposure, the Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society, the Hospital Pharmacy Professional Committee of Chinese Pharmaceutical Association, the Oncology Society of Chinese Medical Association, the Nursing Branch of China International Exchange and Promotive Association for Medical and Healthcare, and Chinese Pharmacological Society Professional Committee of Drug-induced Diseases formulated the Management guidelines for preventing exposure to antineoplastics, which was published in the 1st issue of Chinese Journal of Cancer Research in 2023. The guideline was developed referring to the World Health Organization handbook for guideline development and other international methodologies and focused on the full-process management of antineoplastics in hospitals. Using the Delphi method, clinical questions and 14 recommendations were formulated. This paper interprets 14 recommendations, hoping to help promote the implementation of the guideline.