Expert consensus on off-label drug use in the three Northeastern provinces of China（solid tumors and hematology） / 中国药房

OBJECTIVE To provide theoretical basis for the rational use of drugs in medical institutions， assist in improving the quality of pharmaceutical services， and thus meet clinical drug demands. METHODS Adopting consensus meetings， Liaoning Pharmaceutical Association，Jilin Pharmaceutical Association and Heilongjiang Pharmaceutical Association collaborated with clinical and pharmaceutical experts in the region to compile the expert consensus on off-label drug use in the three Northeastern provinces of China after many votes and discussions by collecting and collating the information related to off-label drug use in medical institutions from the three northeastern provinces of China，and referring to and citing off-label drug use stated in some expert consensus and medication catalog. RESULTS Finally， a total of 198 pieces of off-label drug use information for 70 drugs were included in the two sections of solid tumors and hematological diseases in Consensus of Experts on Drug Use beyond the Instructions in the Three Provinces of Northeast China. CONCLUSIONS Consensus of Experts on Off-label Drug Use in the Three Northeastern Provinces of Northeast China （solid tumors and hematology）offers a theoretical foundation for rational drug use in the treatment of solid tumors and hematological diseases within medical institutions，and has a positive significance in improving the effectiveness and safety of drug treatment.

Recommendations on off-label antibiotics use in PICU / 中国小儿急救医学

Off-label antibiotics use in pediatric intensive care unit is not rare.Off-label antibiotics use is due to indication, age, dosage, frequency, route and method of administration, course of treatment, etc.It is necessary and reasonable for off-label antibiotics use in clinical practice, but there are also some risks.Off-label antibiotics use in clinical practice should follow the corresponding principles and standardized management.Drug treatment decisions should always be made on the basis that the individual child would be ultimately benefit.

Correlation analysis between the judgment of medical damage liability disputes related to off-label drug use and evidence-based evidence / 中国药房

OBJECTIVE To explore wheth er there is a relationship between the judgment results of medical damage liability disputes related to off-label drug use and evidence-based evidence. METHODS By searching for medical damage liability disputes related to off-label drug use up to 2021 on pkulaw.cn ，documents were extracted to record objective factors ，subjective factors and judgment results ；whether there was evidence-based evidence was judged according to Off-label Drug Use List and Evidence-based Evaluation Standards for Off-label Drug Use of Guangdong Pharmaceutical Association ；univariate analysis was adopted to test the relationship between the judgment results and evidence-based evidence. RESULTS A total of 57 cases were included. Cases mainly occurred in the eastern China （63.2％）and tertiary hospitals （64.9％），the main appraisal agency was the appraisal center or institute（61.4％），and the most common type of off-label drug use was overdose drug use （45.6％）. Among the judgment results ， 23 cases（40.4％）of off-label drug use had a causal relationship with medical damage ，most of the responsibility of doctors was secondary responsibility （28.1％），and the actual compensation amount of the most cases were less than 100，000 yuan（54.4％）. There were 25 cases（43.9％）with evidence-based evidence. Univariate analysis found that for off-label drug use the claim amount of the case with evidence-based evidence was significantly higher than that of the case without evidence-based evidence （P＝ 0.040），and there was no significant correlation between evidence-based evidence and the actual compensation amount of the case （P＝0.741），causality determination （P＝0.256），liability type （P＝0.598）or appraisal agency （P≥0.260）. CONCLUSIONS There is no significant correlation between the judgment results of medical damage liability disputes related to off-label drug use and evidence-based evidence ，indicating that there may be certain differences between judicial trials and medical science. The off-label drug use should be regulated by establishing a complete off-label drug use management system and standardizing informed consent procedure for off-label drug use. 1610307322@pku.edu.cn

Retrospective investigation and analysis of off-label drug use for tic disorder in a tertiary women’s and children’s hospital / 药学实践杂志

Objective To analyze the current situation of off-label drug use for tic disorder in a tertiary maternity and child hospital, so as to promote clinical safe and rational drug use. Methods Through the hospital information system, the pediatric outpatient prescriptions diagnosed with tic disorder from July 2019 to August 2020 were selected, and the prescriptions of off-label use was evaluated according to the 2020 off-label drug management regulations. Results A total 1251 pediatric prescriptions diagnosed with tic disorder were collected. The incidence of off-label drug use was 29.58%. The main types of off-label were over-indications and over-age. The main varieties of off-label drug use were risperidone tablets (47.84%) and aripiprazole tablets (43.74%). Conclusion The off-label use of drug for tic disorder in pediatric outpatient department of our hospital is relatively common，and it is necessary to standardize the management of off-label drug use to ensure rational drug use.

Analysis of the safety and efficacy of moxifloxacin in the treatment of severe Mycoplasma pneumoniae pneumonia in children / 中华急诊医学杂志

Objective:To investigate the safety and efficacy of moxifloxacin in children with severe Mycoplasma pneumoniae pneumonia (SMPP).Methods:The patients with SMPP in the Pediatric Intensive Care Unit of Beijing Children's Hospital between January 2017 and April 2020 were retrospectively analyzed. Clinical data were collected to assess therapeutic efficacy, analyze drug safety and summarize positive rate of macrolide-resistant Mycoplasma pneumoniae genes mutation.Results:Thirty-nine children diagnosed SMPP treated with moxifloxacin were included. The positive rate of macrolide-resistant Mycoplasma pneumoniaegenes mutation was 95.2%. In the 39 patients, 6 (15.4 %) were cured, 29 (74.4 %) were effective, 2 (5.1 %) were no response, 2 (5.1 %) were discharged automatically during treatment with moxifloxacin, and the overall response rate was 89.8 %. The situations of consciousness, skin, joint, heart rhythm and gastrointestinal function were carefully observed; Blood routine test, liver and kidney function were closely monitored. There were no adverse drug reactions in the period of medication. No children were discontinued due to adverse reactions.Conclusions:Moxifloxacin can improve efficacy and prognosis for pediatric patients with SMPP. There are no drug adverse reactions during treatment with moxifloxacin, indicating that short-term medication is safe. The application of quinolones in pediatric patients is off-label drug use, and clinical pharmacists should assist clinicians in reducing medical risks.

Common Drugs with Effective Off-Label Uses

The term off-label drug use (OLDU) is utilized broadly in the medical literature. It is a polarizing term since it may be related to incredible advantage or harm to patients. OLDU is defined as drug uses that not included in the indications or dosage regimens listed in the drug labeling. The main issue with off-label use is that there is insufficient information supportsthe use ofthe drug so this review aims to give brief information about some common drugs with effective and useful off-label uses based on scientific study and to encourage the researcher toprovidesufficientinformation for the physician and health care providersaboutoff-label uses to decrease the risk of harm to the patients. There are many drugs with various off-label uses that play an important role clinically such as using atorvastatin in chronic heart failure (CHF) due to its pleiotropic action also it can show a significant reduction in the frequency of hospitalization due to CHF exacerbation. However, that make off-label uses an important is several diseases do not have approved drugs, partly because the diseases are rare or conducting clinical trials and marketing the drug for such diseases may not be gainful.

Off-label drug use in the treatment of rare diseases:the current situation / 国际药学研究杂志

The diagnosis and treatment of rare diseases are a significant social public health work. Due to the low variety and poor accessibility of orphan drug, off-label use is common in the field of rare diseases at home and abroad. Off-label use may be the effective treatment for life-threatening diseases in patients with rare diseases, but it also raises issues related to drug safety and efficacy, medical liability and drug reimbursement, so the supervision of off-label drug use is of particular importance. This article reviews the current situation of off-label drug use and their application in thefield of rare diseases treatment, hoping to arouse widespread concern in society and ensure medication safety for patients with rare diseases through the joint efforts of medical institutions and regulatory agencies.

Investigation and Analysis of the Prescriptions of Outpatient/Emergency Microecological Preparations in 5 Children’s Hospitals / 中国药房

OBJECTIVE： To investigate the situation and problems of clinical microecological preparations in pediatrics department of China， and to provide reference for rational application of microecological preparations in children. METHODS： Outpatient/emergency prescriptions of microecological preparations during Jan.-Mar. 2019 were retrieved from information system of 5 “Third Grade Class A” children hospitals， and were investigated and analyzed in respects of the type of microecological agents， age distribution， clinical diagnosis， drug combination， off-label medication， etc. RESULTS： A total of 74 210 outpatient/emergency prescriptions were collected， involving 18 kinds of microecological preparations. Among them， Clostridium butyricum combined viable powder ranked first （31 146， accounting for 41.97％）， followed by Brucella yeast powder （14 289， accounting for 19.25％） and Compound Lactobacillus acidophilus tablets （10 281， 13.85％）. The age of children was less than 18 years old， and the proportion of children aged 1-＜3 years old was the highest （33 753， 45.48％）. The most common clinical diagnosis     was digestive tract diseases （54 009， 72.78％）， followed    by respiratory infectious diseases （11 744， 15.83％）. In combination with microecological agents， there were Chinese patent medicine for invigorating the spleen and stomach     （18 546， 24.99％）， antibacterial medicine （10 595， 14.28％） and oral rehydration salt Ⅲ （8 238， 11.10％）. Off-label drug use was found in 19 532 prescriptions （26.32％）， mainly manifesting as super-indications （15 590， 21.01％）， super-usage and dosage （8 098， 14.52％）， super crowd medication （48， 3.91％） was found in a few prescriptions. CONCLUSIONS： There is a high incidence of off-label use of microecological agents in children. Medical staff should standardize prescription behavior and promote rational use of drugs. At the same time， the improvement of the information of children’s medication in drug instructions to ensure the safety and effectiveness of children’s medication should be encouraged.

Practice and Exploration of the Construction of Management System for Off-label Drug Use in Our Hospital / 中国药房

OBJECTIVE： To establish the management system for off-label drug use in a medical institutions， and to standardize the behaviors of off-label drug use and improve the rational drug use. METHODS： Based on evidence-based researches for off-label drug use， management system of off-label drug use was established in our hospital， and off-label drug use management was carried out. The effects of management system were evaluated with the number of records for off-label drug use and pass rate of approval as indexes. RESULTS： Since the year of 2011， the management system for off-label drug use had gradually established and improved in our hospital； the mode of registration and approval for off-label drug use was established by based on a multi-disciplinary team management and quality classification for clinical evidence. Up to 2016， a total of 252 records for off-label use were submitted， among which 159 （accounting for 59.77％） were for pediatrics and 93 （accounting for 34.96％） were for gynecology and obstetrics. Among the submitted records， 181 had passed the examination and approval， and the pass rate was 64.29％. Special prescription comments indicated that the numbers of off-label use medical orders in inpatient medical orders showed a downward trend， and the proportion of recorded medical orders of off-label use had increased from 17.33％ in 2013 to 84.00％ in 2016. CONCLUSIONS： The management system for off-label drug use in medical institutions can effectively improve the clinical understanding of off-label drug use， standardize the behavior of off-label drug use.

Application of quinolones in children with severe infection / 中华急诊医学杂志

Objective To analyze the efficacy and safety of quinolones in children with severe infection. Methods Patients with severe infections treated in the Pediatric Intensive Care Unit of Beijing Children's Hospital from November 2016 to January 2018 were enrolled. The clinical data were collected and analyzed. Results Totally 24 children were treated with quinolones, including levofloxacin, ciprofloxacin and moxifloxacin. Patients with poor initial treatment were treated with levofloxacin or ciprofloxacin on the basis of drug sensitivity for bacterial infections. Moxifloxacin was used to treat Mycoplasma pneumoniae infection in patients poorly treated by macrolides antibiotics or macrolide-resistance gene positive. Among the 24 cases, 1 case (4.2 ％) was cured, 19 cases (79.1 ％) treated effectively, 1 case had no response (4.2 ％), and 3 cases (12.5 ％) discharged automatically during treatment, with a response rate of 83.3 ％. The consciousness, skin, joint and gastrointestinal function were closely observed; blood routine test, liver and kidney function were closely monitored. There were no adverse drug reactions during the period of medication. Conclusions Quinolones can improve efficacy and prognosis for pediatric patients with severe infections. There are no drug related adverse reactions, indicating a safe short-term use. The use of quinolones in children is super-instructive, and clinical pharmacists should assist physicians in doing related work and reduce medical risks.

Ethical Reflections on the Enlightenment of American Off-Label Drug Use to Our Country / 中国医学伦理学

Off-label drug use to some extent meets the clinical medication,achieves the most needed treat-ment of patients and promotes the development of medicine,but there exists certain risks at the same time.Through the analysis of the phenomenon of off-label drug use,from the perspective of medical ethics,this paper proposed that it should adhere to the principles of beneficence and respect,specifically,correcting the motives of off-label drug use,strict review of supporting evidence,ensuring patient's informed consent,strengthening ethical review andintroducing the insurance sharing mechanism,so as to achieve both the guarantee of patient's medication safety and the aversion of medical personnel's practice risks.

Analysis on 201 Cases of Off-label Use and Related Factors for Adverse Reactions of Lobaplatin for Injection in a Hospital / 中国药师

Objective:To analyze the off-label use and adverse reactions of lobaplatin for injection to provide reference for the rational use in clinic. Methods:A retrospective review was conducted on the inpatient medical records (201 cases) with lobaplatin for injection from November 2016 to July 2017 in a hospital and analyzed the characteristics of adverse drug reactions/events (ADR/ADE) with the help of SPSS software. The ADRs were performed correlation factor analysis.Results:The off-label ratio of the indication,administration route and solvent for lobaplatin was 89.55%,18.41% and 47.26%,respectively. The rate of adverse events was 63.18%. The main adverse reactions were blood and lymphatic system disorders and hepatobiliary system damage,and the manifestations were lymphocyte decrease(40.80%),hemoglobin(23.88%),white blood cell decrease (19.90%) and platelet decrease (15.92%) and AST increase (10.45%). No grade 5 adverse event happened, however, new adverse reactions,such as palpitation, dyspnea, harshness, etc were shown. The use of 0.9% sodium chloride injection as the solvent for lobaplatin may be a risk factor for ADRs. Conclusion:Most of the medical orders with lobaplatin for injection contain off-label use,and the rate of adverse events is as high as 63.18%. The use of 0.9% sodium chloride injection as the solvent for lobaplatin may be a risk factor for ADRs.

Analysis on the Refused Payment in Medical Insurance Drugs in One Hospital in 2016 / 中国药师

Objective:To analyze the refused payment in medical insurance drugs in our hospital in 2016 to promote the rational drug use.Methods:The refused payment in medical insurance drugs was analyzed , the reasons were summarized and the medication rationality was analyzed as well .Results:There were 372 cases of refused payment in medical insurance drugs in 2016 , and among them, 281 cases were with excessive medication accounting for 75.54％.There were 46 cases of off-label drug use, which accounted for 54.33％in the whole refused sum.The other reasons for the refused payment in medical insurance drugs included contraindication use of medication and violation of ladder medication etc .Conclusion:In the diagnosis and treatment process , doctors should be famil-iar with and follow the medical insurance payment system .The current health insurance payment system also requires a combination of medical technology , pharmacy economics and Chinese patient data .Medicare payment system needs to be improved by information technology.At the same time, pharmacists should play active role , and medical institutions should be encouraged to take effective measures to promote clinical rational drug use , which can promote the maximum normative treatment for each patient .

How to regularize the off-label drug use in children / 中国小儿急救医学

Pediatric information for medication is insufficiency in the instruction due to the absence of clinical study special for children. Off-label drug use is ubiquitous in pediatric clinical works,and likely to medical risks and medical disputes. We should be confronted with the reality to standardize the off-label drug use. The enactment of the law,norms and standards setting,medication information study,and intensive super-vision are the key strategies for off-label drug use in children.

Analysis of related policies in China and abroad on pediatric off-label drug use / 中国小儿急救医学

The problem of off-label drug use is particularly prominent among children. The main rea-son is that children are not routinely tested in drug clinical trials and lack of medication information in chil-dren′s instructions. In view of this,a number of countries have formulated relevant policies to promote the clinical research of children′s drugs,to improve the information of children′s medication in the instructions, and to standardize the pediatric off-label uses. There are no current laws and regulations related on paediatric off-label drug uses in China,we should learn from the experience of other countries,make laws and regula-tions for pediatrics, implement pediatric drug policy,promote pediatric clinical research data to improve, to guide pediatric drug information more scientificly and sufficiently. Only multi-department cooperation can en-sure children′s safety,rational drug use,and promote the healthy growth of children.

Analysis of off-label use of anti-infective drugs in children / 中国小儿急救医学

Off-label use or unlicensed use of anti-infective drugs is most commonly in children both in the outpatient and inpatient settings. Off-label anti-infective drug use is due to dosage,frequency,patient age,indication,route of administration,or contraindications. Off-label use of drugs does not necessarily mean unsafe use. Off-label drug use should be based on high-quality evidence;use within the context of a formal research proposal and exceptional use.

Risk and prevention of off-label drug uses / 中国小儿急救医学

Pediatric off-label drug use is common especially at critical care and emergency field. Off-label drug use has its rationality and necessity. However, its risks must be taken seriously and actively prevented. We should concern the risks of off-label prescriptions and prevent them in advance. Standardizing the implementation plan and procedures of clinical off-label drug use from national regulations to medical institutions could make benefits for both patients and physicians. It will improve medication safety eventually.

Pharmaceutical Analysis of Judicial Precedents Involving Off-label Drug Use / 中国药学杂志

OBJECTIVE: To analyze 13 judicial precedents involving off-label drug use and explore the legal interpretation on off-label drug use in China in order to provide experience for establishment of off-label drug use and clinical application. METHODS: Based on the law databases (China Judgements Online, Chinalawinfo, Jufaanli, Itslaw), 13 cases were searched and screened involving legal off-label drug use. The relationship was investigated and discussed between different results and characteristics of the 13 cases. RESULTS: In 13 cases, there are 2 cases probably reasonable for off-label use, 2 cases unreasonable but not correlated with patients′ outcomes, 9 unreasonable and with a causal relationship with patients′ outcomes. In the 9 unreasonable cases, there are 4 cases without sufficient evidence, 3 cases without informed consent, 1 case lack of monitoring after off-label use, 1 case with idiosyncratic reaction, and 1 case not consistent with the label of the drug used. CONCLUSION: Major deficiencies of off-label drug use in China are without sufficient evidence, lack of informed consent and with uncompleted system on off-label drug use. Establishing more completed and detailed system, investigating enough clinical evidence, better informed consent and monitoring after off-label use are important measurements to ensure safety on off-label drug use.

Present Situation and Countermeasures of Conflict between Off-label Drug Use and Judicial Evaluation / 中国药房

OBJECTIVE:To provide suggestions for standardizing and protecting the off-label drug use. METHODS:Accord-ing to the field interviews with pharmacists and lawyers,the present situation of off-label drug use in judicial practice at home and abroad,and relevant countermeasures were put forward. RESULTS & CONCLUSIONS:At present,there was no mechanism for off-label drug use in the laws and regulations in China;there was only"special circumstances"statement in sporadic terms,while lacking explanation. In judicial practice of medical disputes,judges had different identifications in various references,such as the le-gality of routine and guidelines,teaching medical materials,clinical pathways,and internal regulations of medical institutions pre-pared by authoritative departments. Meanwhile,the judicial environment of hearing cases by identification made the off-label drug use had impartial adjudication. Legislation in 6 countries,including America,allows reasonable off-label drug use;FDA required off-label drug use must be for the benefit of patients rather than clinical trials,and it also should protect the patient's right to know. China should establish the authority specification of off-label drug use,providing scientific identification procedures,protect the patient 's informed consent by law. Medical institutions should develop relevant management system and processes to regulate medical prac-tices and ensure off-label drug use in line with the interests of doctors and patients.

Multi-center Survey on Off-label Drug Use of Ambroxol Hydrochloride Injection / 中国药房

OBJECTIVE:To investigate off-label drug use of Ambroxol hydrochloride injection,and to provide reference for further evidence-based evaluation on rationality and standardized management of off-label drug use. METHODS:All medical orders for inpatients receiving Ambroxol hydrochloride injection were selected from 10 hospitals of Guangdong province during Apr. 2014 to Mar. 2015. Situation of drug use in different categories of departments was summarized,the incidence of off-label administation route and off-label dosage were analyzed;according to drug package inserts,prescription daily dose(PDD)and drug utilization in-dex(DUI)were calculated for each category of department,and the degree of off-label dosage was evaluated. RESULTS:A total of 761 821 person·day who used Ambroxol hydrochloride injection was included. Off-label drug use occurred in each category of departments,and the incidence of off-label drug use was 62.10%. The incidence of off-label administration route was 40.51%, mainly atomization inhalation;the incidence of it was the high-est in gynecology and obstetrics department(92.70%).The in-cidence of off-label dosage was 36.30%,and the incidence of it was the highest in cardiothoracic surgery department (85.36%). Departments whose PDDs were higher than the drug package inserts were cardiothoracic surgery department,ICU,surgical department,cardiovascular medicine department,emer-gency department,department of internal medicine and pediatrics department.CONCLUSIONS:Off-label drug use of Ambroxol hy-drochloride injection is common,and the effectiveness,safety and necessity remain controversial,which need to be proved by multi-center randomized controlled prospective trial.