The interleukin-6 (IL-6) pathway plays a crucial role in various rheumatic diseases. Tocilizumab, a biologic targeting IL-6 receptor, has been widely used in clinical practice, though it\'s officially approved in China for only three indications. To address clinical challenges associated with the off-label use of tocilizumab in treating rheumatic diseases, the Committee of Chinese Primary Health Care Foundation for Rheumatologists and Immunologists engaged multidisciplinary experts and highlight 12 related clinical issues. We aggregated the drug specifications, the guidelines for clinical management of rheumatic diseases and the evidence from clinical research. Recommendations were formed through voting with the consensus conference method incorporating the Oxford evidence-based medicine criteria to evaluate the strength of evidence and recommendations. We have formulated 10 recommendations for off-label use of tocilizumab related to giant cell arteritis, polymyalgia rheumatica, Takayasu arteritis, systemic sclerosis, adult-onset Still\'s disease, rheumatoid arthritis, and juvenile idiopathic arthritis. This consensus aims to provide references for the rational use of tocilizumab in clinical practice and enhance pharmacovigilance monitoring.
白细胞介素-6（IL-6）通路参与多种风湿性疾病，靶向IL-6受体的生物制剂托珠单抗临床使用广泛，但在国内仅获批3种适应证。为规范临床托珠单抗超说明书用药治疗风湿性疾病，中国初级卫生保健基金会风湿免疫学专业委员会组织国内相关专业的专家就调研的12个临床问题，检索国内外药品说明书、风湿性疾病指南共识及临床研究等证据，采用牛津大学循证医学中心分级系统进行证据评价和推荐强度分级，并经共识专家组讨论、投票，最终形成10条推荐意见，涉及巨细胞动脉炎、风湿性多肌痛、大动脉炎、系统性硬化病、成人斯蒂尔病、类风湿关节炎和幼年特发性关节炎，旨在为临床医师提供合理用药依据并为药学部门管理提供参考。.

Trigeminal neuralgia is characterized by severe, lightning-like attacks of pain, which are mandatory for the diagnosis. The pain typically occurs on one side and is often triggered by simply touching the face, chewing or talking. In acute exacerbations, this can also hinder food and fluid intake, resulting in a life-threatening clinical picture. A distinction is made between classical, secondary and idiopathic trigeminal neuralgia. For the diagnosis of trigeminal neuralgia, the medical history and imaging procedures are key for classification. The only active substances approved for the treatment of trigeminal neuralgia in Germany are carbamazepine and phenytoin, which is why off-label drugs often need to be used if there is no or insufficient effect or inacceptable side effects. Cooperation between research and clinical practice to improve the care of affected patients is therefore essential.
UNASSIGNED: Die Trigeminusneuralgie ist durch heftige, blitzartige Schmerzattacken gekennzeichnet, die für die Diagnose obligatorisch sind. Typischerweise treten die Schmerzen einseitig auf, oft werden sie durch einfache Berührungen des Gesichts, Kauen oder Sprechen ausgelöst. Dies kann bei akuten Exazerbationen auch die Nahrungs- und Flüssigkeitsaufnahme behindern, sodass es zu einem lebensbedrohlichen Krankheitsbild kommen kann. Es wird zwischen der klassischen, der sekundären und der idiopathischen Trigeminusneuralgie unterschieden. Für die Diagnose der Trigeminusneuralgie ist die Anamnese entscheidend, für die Einteilung sind es bildgebende Verfahren. Die einzigen in Deutschland zugelassenen Wirkstoffe zur Behandlung der Trigeminusneuralgie sind Carbamazepin und Phenytoin, weshalb häufig bei fehlendem oder unzureichendem Wirkeffekt bzw. bei inakzeptablen Nebenwirkungen Off-label-Medikamente eingesetzt werden müssen. Eine Zusammenarbeit von Forschung und klinischer Praxis zur Verbesserung der Versorgung betroffener Patienten ist daher essenziell.

BACKGROUND: Despite being a global public health concern, there is a research gap in analyzing implementation strategies for managing off-label drug use in children. This study aims to understand professional health managers\' perspectives on implementing the Guideline in hospitals and determine the Guideline\'s implementation facilitators and barriers.
METHODS: Pediatric directors, pharmacy directors, and medical department directors from secondary and tertiary hospitals across the country were recruited for online interviews. The interviews were performed between June 27 and August 25, 2022. The Consolidated Framework for Implementation Research (CFIR) was adopted for data collection, data analysis, and findings interpretation to implement interventions across healthcare settings.
RESULTS: Individual interviews were conducted with 28 healthcare professionals from all over the Chinese mainland. Key stakeholders in implementing the Guideline for the Management of Pediatric Off-Label Use of Drugs in China (2021) were interviewed to identify 57 influencing factors, including 27 facilitators, 29 barriers, and one neutral factor, based on the CFIR framework. The study revealed the complexity of the factors influencing managing children\'s off-label medication use. A lack of policy incentives was the key obstacle in external settings. The communication barrier between pharmacists and physicians was the most critical internal barrier.
CONCLUSIONS: To our knowledge, this study significantly reduces the implementation gap in managing children\'s off-label drug use. We provided a reference for the standardized management of children\'s off-label use of drugs.

Patients with cancer may be given treatments that are not officially approved (off-label) or recommended by guidelines (off-guideline). Here we present a data science framework to systematically characterize off-label and off-guideline usages using real-world data from de-identified electronic health records (EHR). We analyze treatment patterns in 165,912 US patients with 14 common cancer types. We find that 18.6% and 4.4% of patients have received at least one line of off-label and off-guideline cancer drugs, respectively. Patients with worse performance status, in later lines, or treated at academic hospitals are significantly more likely to receive off-label and off-guideline drugs. To quantify how predictable off-guideline usage is, we developed machine learning models to predict which drug a patient is likely to receive based on their clinical characteristics and previous treatments. Finally, we demonstrate that our systematic analyses generate hypotheses about patients\' response to treatments.

Sjögren\'s syndrome (SjS) is one of the most prevalent rheumatic diseases. Off-label drug use is very common in the clinical practice of the treatment of SjS. In order to establish evidence-based justifications and systematically evaluate the off-label drug use in SjS treatment, the Committee of Chinese Primary Health Care Foundation for Rheumatologists and Immunologists referred to published guidelines, consensus statements, and case series, and reevaluated the outcomes of the randomized controlled trials about the marketed immunosuppressive drugs treating SjS. The single-item breakdown of the Sjögren\'s tool for assessing response (STAR) which was proposed in 2022 was employed as the outcome. The committee established the corresponding clinical questions based on the population, intervention, comparison, and outcome (PICO) principle, and then carried out evidence retrieval, and synthesized meta-analysis using the grading of recommendations, assessment, development, and evaluation (GRADE) methodology. Finally, 21 recommendations addressing twelve clinical questions were formed which included two strong recommendations, fourteen weak recommendations, and five consensus-based recommendations. The overarching objective of the guideline is to provide clinicians with a rational basis for medication selection and to offer guidance to pharmacy departments for management purposes.
干燥综合征（SjS）是最常见的风湿免疫病之一，临床实践中普遍存在超说明书用药现象。为此，中国初级卫生保健基金会风湿免疫学专业委员会组织专家通过循证查证及系统评价超药品说明书用药治疗SjS的依据，除参考已公开发布的指南、共识、诊疗规范等外，还对已上市的免疫抑制药物治疗SjS的随机对照试验进行再评估，采用2022年提出的评价SjS治疗应答新工具（STAR）的单项分解条目作为结局，设计相应的临床问题，依据人群、干预、对照和结局（PICO）原则完成证据检索、荟萃分析及推荐意见分级的评估、制订及评价（GRADE）分级与推荐，最终形成针对12个临床问题的21条推荐意见，包括2条强推荐、14条弱推荐和5条基于共识的推荐，旨在为临床医师提供合理用药依据并为药学部门管理提供参考。.

The study aimed to develop international consensus recommendations on the safe use of lumen-apposing metal stents (LAMSs) for on- and off-label indications.
Based on the available literature, statements were formulated and grouped into the following categories: general safety measures, peripancreatic fluid collections, endoscopic ultrasound (EUS)-biliary drainage, EUS-gallbladder drainage, EUS-gastroenterostomy, and gastric access temporary for endoscopy. The evidence level of each statement was determined using the Grading of Recommendations Assessment, Development, and Evaluation methodology.International LAMS experts were invited to participate in a modified Delphi process. When no 80% consensus was reached, the statement was modified based on expert feedback. Statements were rejected if no consensus was reached after the third Delphi round.
Fifty-six (93.3%) of 60 formulated statements were accepted, of which 35 (58.3%) in the first round. Consensus was reached on the optimal learning path, preprocedural imaging, the need for airway protection and essential safety measures during the procedure, such as the use of Doppler, and measurement of the distance between the gastrointestinal lumen and the target structure. Specific consensus recommendations were generated for the different LAMS indications, covering, among others, careful patient selection, the preferred size of the LAMS, the need for antibiotics, the preferred anatomic location of the LAMS, the need for coaxial pigtail placement, and the appropriate management of LAMS-related adverse events.
Through a modified international Delphi process, we developed general and indication-specific experience- and evidence-based recommendations on the safe use of LAMS.

In 2018, Chinese Society of Tuberculosis, Chinese Medical Association organized and wrote the Expert consensus on off-label use of antituberculosis drugs, which covered more comprehensively the contents related to off-label use of antituberculosis drugs, and was the basis for clinical workers to exceed the drug instructions for the use of antituberculosis treatment in irreplaceable cases, and was also a good regulation for off-label use, which had a great guiding effect on clinical work. In the last four years, with the reported national and international research results, the anti-tuberculosis treatment drugs have been adjusted and there are more new advances in the use of some drugs. For this reason, Chinese Society for Tuberculosis, Chinese Medical Association has updated the expert consensus on off-label use of antituberculosis drugs. This consensus included isoniazid, rifamycins (rifampicin, rifapentine), fluoroquinolones (levofloxacin, moxifloxacin), linezolid, clofazimine, bedaquiline, delamanid, aminoglycosides (streptomycin, amikacin), and β-lactam antibacterial (imipenem/cilastatin, meropenem), and a total of 13 drugs in 9 categories were reviewed for off-label use, overdose, route of administration and patient populations. The GRADE evidence classification method was used to conduct a systematic evaluation of evidence quality and recommended strength. The revised consensus provides a reference for tuberculosis prevention and control workers in China for standardized drug use and rationalized treatment, and therefore for improved effectiveness and better patient benefits.
2018年中华医学会结核病学分会组织撰写了《抗结核药物超说明书用法专家共识》，较为全面地涵盖了抗结核药物超说明书使用的相关内容，是临床工作者在无可替代情况下超出药物说明书抗结核治疗用药的依据，也是对超说明书用药情况的良好规范，对临床工作具有良好的指导作用。4年来，随着国内外研究成果的不断报道，抗结核治疗药物有所调整，多种药物的使用方法也已有所改进。为此，中华医学会结核病学分会对《抗结核药物超说明书用法专家共识》进行了更新。本共识对异烟肼、利福霉素类药物（利福平、利福喷丁）、氟喹诺酮类药物（左氧氟沙星、莫西沙星）、利奈唑胺、氯法齐明、贝达喹啉、德拉马尼、氨基糖苷类药物（链霉素、阿米卡星）、β-内酰胺类药物（亚胺培南/西司他丁、美罗培南）共9类13种药物的超适应证、超剂量用法、超用药途径、超适用人群等的内容进行了整理与修订，并按照GRADE证据分级方法进行了证据质量分级和推荐强度的系统评价，供我国结核病防治工作者借鉴与参考，以规范用药、合理治疗、提升疗效，更好地实现患者获益。.

In recent years, the emergence of newly detected pathogens and the increase of drug resistant bacterial bring serious challenges for the diagnosis and treatment of infectious diseases. Tetracycline drugs are widely used in clinical practice, and the varieties of these drugs are constantly being updated. However, there is still a lack of guidance documents for the rational clinical application of tetracycline drugs in China. Meanwhile, some healthcare workers have doubts about their pharmaceutical characteristics, timing and methods of clinical application. In order to further standardize the clinical application of tetracycline drugs and provide professional evidence-based medicine suggestions for medical personnel in medical institutions, under the leadership of Hospital Infection Control Branch of Chinese Preventive Medicine Association and Clinical Pharmacology Branch of Chinese Pharmacological Society, experts from areas of infection, respiratory medicine, critical care medicine, emergency, infection control, pharmacy and other disciplines organized a consensus meeting and formulated multidisciplinary expert consensus on the rational use of tetracyclines commonly used in clinical practice. This expert consensus is based on the pharmaceutical characteristics of tetracyclines commonly used in China, the mechanism of action and drug resistance status of tetracyclines, combined with the infection site, pathogen characteristics and bacterial drug resistance. This expert consensus also pays attention to special populations and off-label drug use, and integrates domestic and foreign recommendations and the latest evidence-based medicine evidence, and 17 expert consensus opinions for clinical physicians, pharmacists, and other professionals in medical institutions to refer to were formed. In view of the particularity and complexity of infectious diseases and the individual differences of patients, in order to benefit patients, individualized anti-infection strategies should be implemented.
近年来随着新检出病原体的出现和细菌耐药性的增加，感染性疾病的诊断和治疗面临着严峻挑战。四环素类药物在临床应用广泛，药物品种也在不断更新，我国尚缺乏四环素类药物临床合理应用的指导性文件，部分医务人员对其药学特点和临床应用时机及用法存在疑惑。为进一步规范四环素类药物的临床应用，为各级医疗机构医务人员提供专业的循证医学建议，中华预防医学会医院感染控制分会和中国药理学会临床药理分会牵头，组织感染科、呼吸科、重症医学科、急诊科、感染控制中心、药学部等多个学科领域专家经过共识会议制订了临床常用四环素类药物合理应用多学科专家共识。本专家共识以国内常用的四环素类药物的药学特性为基础，以四环素类药物作用机制和耐药现状为依据，结合感染部位、病原体特点及细菌耐药性，关注特殊人群和超说明书用药，整合国内外指南推荐意见和最新循证医学证据，形成可供医疗机构临床医师、临床药师等专业人员参考的17条专家共识意见。鉴于感染性疾病的特殊性、复杂性及患者的个体差异性，为使患者获益，本专家共识形成的意见需实施个体化的抗感染策略。.

UNASSIGNED: Adults with intellectual disabilities have an increased vulnerability to mental health problems and challenging behaviour. In addition to psychotherapeutic or psychoeducational methods, off-label pharmacotherapy, is a commonly used treatment modality.
UNASSIGNED: The aim of this study was to establish evidence-based guideline recommendations for the responsible prescription of off-label psychotropic drugs, in relation to Quality of Life (QoL).
UNASSIGNED: A list of guidelines was selected, and principles were established based on international literature, guideline review and expert evaluation. The Delphi method was used to achieve consensus about guideline recommendations among a 58-member international multidisciplinary expert Delphi panel. Thirty-three statements were rated on a 5-point Likert-scale, ranging from totally disagree to totally agree, in consecutive Delphi rounds. When at least 70% of the participants agreed (score equal or higher than 4), a statement was accepted . Statements without a consensus were adjusted between consecutive Delphi rounds based on feedback from the Delphi panel.
UNASSIGNED: Consensus was reached on 4 general:the importance of non-pharmaceutical treatments, comprehensive diagnostics and multidisciplinary treatment. Consensus was reached in 4 rounds on 29 statements. No consensus was reached on 4 statements concerning: freedom-restricting measures, the treatment plan, the evaluation of the treatment plan, and the informed consent.
UNASSIGNED: The study led to recommendations and principles for the responsible prescription - aligned with the QoL perspective - of off-label psychotropic drugs for adults with intellectual disabilities and challenging behaviour. Extensive discussion is needed regarding the issues on which there was no consensus to furthering the ongoing development of this guideline.

Off-label medicines use is a common and sometimes necessary practice in many populations, with important clinical, ethical and financial consequences, including potential unintended harm or lack of effectiveness. No internationally recognized guidelines exist to aid decision-makers in applying research evidence to inform off-label medicines use. We aimed to critically evaluate current evidence informing decision-making for off-label use and to develop consensus recommendations to improve future practice and research.
We conducted a scoping review to summarize the literature on available off-label use guidance, including types, extent and scientific rigor of evidence incorporated. Findings informed the development of consensus recommendations by an international multidisciplinary Expert Panel using a modified Delphi process. Our target audience includes clinicians, patients and caregivers, researchers, regulators, sponsors, health technology assessment bodies, payers and policy makers.
We found 31 published guidance documents on therapeutic decision-making for off-label use. Of 20 guidances with general recommendations, only 35% detailed the types and quality of evidence needed and the processes for its evaluation to reach sound, ethical decisions about appropriate use. There was no globally recognized guidance. To optimize future therapeutic decision-making, we recommend: (1) seeking rigorous scientific evidence; (2) utilizing diverse expertise in evidence evaluation and synthesis; (3) using rigorous processes to formulate recommendations for appropriate use; (4) linking off-label use with timely conduct of clinically meaningful research (including real-world evidence) to address knowledge gaps quickly; and (5) fostering partnerships between clinical decision-makers, researchers, regulators, policy makers, and sponsors to facilitate cohesive implementation and evaluation of these recommendations.
We provide comprehensive consensus recommendations to optimize therapeutic decision-making for off-label medicines use and concurrently drive clinically relevant research. Successful implementation requires appropriate funding and infrastructure support to engage necessary stakeholders and foster relevant partnerships, representing significant challenges that policy makers must urgently address.