Clinical comprehensive evaluation of recombinant Mycobacterium tuberculosis fusion protein / 中国药房

OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

Exploration of pharmaceutical service model in multidisciplinary diagnosis and treatment of rare diseases in children / 中国药房

OBJECTIVE To explore the pharmaceutical service model in multidisciplinary diagnosis and treatment （MDT） of rare diseases in children. METHODS Clinical pharmacists of West China Second University Hospital （hereinafter referred to as “our hospital”） participated in the process of MDT of children’s rare diseases. Clinical pharmacists took part in the entire diagnosis and treatment process of children and established the MDT pharmaceutical service model of children’s rare diseases by formulating drug treatment plans based on evidence-based practice， improving the accessibility of drugs， pharmaceutical monitoring and drug treatment management. RESULTS From January 2021 to April 2022， clinical pharmacists of our hospital had participated in a total of 39 cases of rare diseases MDT in children， including 21 hospitalized children with rare diseases and 18 outpatient com children with rare diseases， involving a total of 23 rare diseases. Clinical pharmacists completed 45 pharmaceutical zhanglingli@scu.edu.cn rounds and 26 pharmaceutical consultations for rare diseases inpatients， 25 outpatients’ MDT and 5 pharmaceutical outpatient service for outpatients with rare diseases， 38 medication educations for inpatients and outpatients with rare diseases and 25 follow-up services for out-of-hospital patients. There were 24 cases （61.54%） of off-label drug use， involving 13 rare diseases and 16 therapeutic drugs， among which off-label drug use registration of 11 drugs had been completed or was in progress. The temporary purchase evaluations of 3 drugs had been completed； 268 cases of medical insurance drug and high-value drug prescription had been reviewed. CONCLUSIONS Our hospital have primarily established a loop pharmaceutical service model of MDT for children with rare diseases， which covers inpatients and outpatients. The model improves the availability and standardization of clinical application of therapeutic drugs， and diagnosis and treatment level for children with rare diseases in our hospital.

Systematic Review of Methodological Guidelines for Health Technology Assessment at Home and Abroad / 中国药房

OBJECTIVE：To evaluate guidelines f or health technology assessment （HTA）at home and abroad ，and to provide reference for scientific formulation of HTA guidelines in China. METHODS ：Databases including PubMed ，Embase，Guidenlines International Network and 83 official websites from 26 countries governments and academic organizations were searched to collect HTA guidelines from inception to April 2020. Two reviewers independently screened literature and extracted data ，including basic characteristics， content of guideline and assessment content. Then a descriptive analysis was conducted. RESULTS & CONCLUSIONS：A total of 19 guidelines published during 2001 to 2018 were included ，7 guidelines（36.8％）were published in 2015-2020；in addition to 1 guideline from WHO ，14 guidelines （73.7％）were published in Europeand ，2 guidelines（10.5％） in North America and 1 guideline each from South America and Asia （5.3％）. There were 11 guidelines（57.9％）developed by academic organizations and 8 guidelines（42.1％）by health administration ；11 guidelines（57.9％）were evidence-based ，while the others weren ’t evidence- based （42.1％）. The purpose ，content and object of assessment are demonstrated in 19 guidelines；18 guidelines specified the assessment method （94.7％），and 16 guidelines（84.2％）defined the subject of assessment ；14 guidelines （73.7％）specified the HTA assessment process ；12 guidelines（63.3％）mentioned the conflict of interest in HTA assessment process；7 guidelines（36.8％）mentioned the application of assessment results. There are some differences in the formulation methods and contents of HTA guidelines in foreign countries ，but the core contents ar e basically the same. At present ，there is a lack of HTA guidelines in China. We can refer to foreign guidelines，and establish applicable HTA guidelines which aresuitable for national conditions ，so as to provide scientific guidance for HTA research.

Safety on Chloral Hydrate Oral Solution for Sedative and Hypnotic in Children ：A Systematic Review / 中国药房

OBJECTIVE：To systematically evaluate the safety of Chloral hydr ate（CH）oral solution for sedative and hypnotic in children，and to provide evidence-based reference for clinical use. METHODS ：Retrieved from 9 electronic databases （PubMed， Cochrane Library ，Embase，CINAHL，International Pharmaceuticals ，CNKI，CBM，Wanfang Database ，VIP），3 clinical trial registry platforms （Clinical Trials ，Cochrane Clinical Trial Database ，WHO Clinical Trial Database ）and 18 adverse drug reaction （ADR）monitoring systems （ADR monitoring websites of WHO ，USA，Switzerland，China and other countries/areas/international organizations），during the date of database establishment to March 2019，the reports of randomized controlled trials ，cohort studies，case-control studies ，case series studies ，case reports ， cross-sectional studies and adverse reactions monitoring network of chloral hydrate versus other interventions （blank 85503205。E-mail：chenzhehx@163.com control，placebo or other sedative hypnotics ）for children ’s sedative and hypnotic safety were collected. After data extraction of included literatures met inclusion criteria ，quality mail：zhanglingli@scu.edu.cn evaluation of included s tudies with Cochrane bias risk evaluation manual （RCT），Newcastle-Ottawa scale evaluation tool （Cohort study and case control study ），Australian JBI quality assessment tool （case series study and case report study ），Meta-analysis was performed by Rev Man 5.3 software，or descriptive analysis was conducted. RESULTS ：A total of 54 studies were included ，among which there were 13 RCTs，9 cohort studies ，17 case series studies ，13 case reports ，and 2 reports from ADR monitoring network. Based on the results of RCT and cohort studies ， the incidence of Chloral hydrate oral solution adverse events was 7.25％. There was no statistical significance in the incidence of digestive system [RR ＝0.87，95％ CI（0.14，5.42），P＝0.88]，nervous system [RR ＝0.13，95％ CI（0.01，2.41），P＝0.17]， cardiovascular system [RR ＝2.12，95％ CI（0.08，56.57），P＝0.65] adverse event between Chloral hydrate oral solution and midazolam. The incidence of respiratory system adverse events induced by Chloral hydrate oral solution was higher than that of midazolam [RR ＝3.07，95％CI（1.94，4.86），P＜0.01]. There was no statistical significance in the incidence of digestive system adverse events between Chloral hydrate oral solution and diazepam [RR ＝0.71，95％CI（0.47，1.10），P＝0.13]. There was no statistical significance in the incidence of digestive system ，nervous system and cardiovascular system adverse events between Chloral hydrate oral solution and barbiturates （P＞0.05）. CONCLUSIONS ：Chloral hydrate oral solution is similar to midazolam ， diazepam and barbiturates in terms of digestive ，nervous and cardiovascular systems adverse events ，but the incidence of respiratory system adverse events is higher than midazolam.

Analysis of Medication Therapy Management at Home and Abroad / 中国药房

OBJECTIVE： To descriptively analyze the status quo of medication therapy management （MTM） at home and abroad， and to provide reference for the development of MTM in China. METHODS：Retrieved from PubMed， Embase， Cochrane Library， CNKI， VIP， Wanfang database， CBM，and simultaneously searched Google and Baidu， retrieve time from the database establishment to March 2019， Chinese retrieval words： “medication therapy management”， English retrieval words： “Medication therapy management” “Management”“Medication therapy”“Therapy management”“Medication”“Drug therapy management”， etc. Domestic and foreign MTM literatures were included. Descriptive analysis was conducted in terms of literature publication， research type distribution， disease distribution and the status quo of MTM literatures in women and children. The necessity and feasibility of MTM in the field of women and children were analyzed. RESULTS & CONCLUSIONS： A total of 403 MTM related literatures （344 foreign， 59 domestic） were included. Among them， the foreign MTM literatures had 154 secondary researches and 190 original studies， clinical value， economic value and humanistic value of MTM were studied in repsects of service providers， service objects， service processes， service effects and other parties. Domestic MTM literatures had 37 secondary researches and 22 original researches， which mainly introduced the US MTM， including implementation background， concept， elements， application status， etc.； the significance and prospects of MTM in China were analyzed. Domestic and foreign MTM literatures mostly focused on chronic diseases in the elderly， mainly endocrine and cardiovascular diseases， such as hypertension， diabetes， and kidney disease. 11 studies about women and children MTM were included （women 5 studies and children 6 studies）； 4 of them were review， 5 were cross-sectional studies， and 2 were case reports. The effects of women and children MTM were introduced in the included literatures from the times of interventions， the number of drug-related problems prevention or improvement， the patient’s clinical outcomes， etc. MTM studies have great differences between at home and aboard in terms of the number of literatures， research types and contents. The researches focus on the field of chronic diseases in the elderly， and there is little literature on MTM in the field of women and children. It is necessary to provide MTM services for women and children in the light of the Millennium Development Goals proposed by the United Nations and the increasing problem of women and children medication. It is suggested to use the MTM model to develop women and children chronic disease pharmaceutical service so as to promote the transformation of pharmacists and improve the quality of pharmaceutical care.

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.

Evidence-based Evaluation of Global Existed Diarrhea Guidelines of Children / 中国药房

OBJECTIVE:To evaluate the global existed diarrhea guidelines of children,and provide evidence and methodology reference for clinical practice and the formulation of diarrhea evidence-based guideline of children in China. METHODS:Retrieved from PubMed,Embase,CBM,CNKI,VIP,Wanfang databases and related websites,references included in studies were retrieved additionally from database building to Dec. 2017. The methodological quality of the guideline was evaluated by 2 researchers independently with guideline evaluation toolⅡ(AGREEⅡ). ICC analysis was used to calculate the differences between the evaluation results of 2 researchers and analyze the difference of the guidelines. RESULTS:A total of 1 168 literatures were collected primarily, and 15 guidelines were involved finally,among which 3 guidelines were from USA,2 from British,2 from WHO,each one from Italy,Europe,India,Australia,Malaysia,New South Wales,South Africa and China,respectively. Of 15 guidelines,there were 10 evidence-based guidelines and 5 non-evidence-based guidelines;evidence levels of guidelines and the method of recommendation intensity were different. ICC of 2 researchers were higher than 0.75(P<0.05),indicating good homogeneity among them. The quality of 15 guidelines were not high enough,and the scores of included guidelines in the field of AGREEⅡin descending order were as follows:scope and purpose(84.44%),clarity of presentation(79.82%),stakeholder involvement(45.74%), rigor of development(41.18%), editorial independence (36.39%)and applicability(33.89%). Main prevention and treatment method recommended by guideline included that(1) prevention and treatment of dehydration was the key link in the treatment of children's diarrhea;(2)guidelines generally believed continuous breastfeeding during rehydration could reduce the risk of dehydration in children;(3)zinc preparation was recommended to shorten the course of diarrhea;(4)antibiotics were used rationally, etc. CONCLUSIONS:The quality of global existed diarrhea guidelines of children should be improved. There is no comprehensive diarrhea evidence- based guideline of children in China,and there is a large discrepancy between the situation of pediatric diarrhea therapy in China and WHO standard;it is urgent to establish a standard treatment. It is suggested to formulate high quality pediatric diarrhea guideline in accordance with the national conditions of China,based on standards for international guideline report, comprehensively considering disease burden and characteristics of pediatric diarrhea in China.

Evidence-based Evaluation of Current Global Idiopathic Thrombocytopenia Purpura Guidelines of Children / 中国药房

OBJECTIVE: To evaluate evidence-based guidelines of current global pediatric idiopathic thrombocytopenic purpura (ITP) drug therapy, and to provide evidence-based reference for pediatric ITP diagnosis and treatment, the formulation of guideline in China. METHODS: Retrieved from PubMed, Embase, National Guideline Clearinghouse, Guidelines International Network, TRIP medical database, CBM, CJFD, VIP and WANFANG DATA, etc., the evidence-based treatment guideline involving pediatric ITP were included, and methodological quality of the guideline was evaluated by using AGREE Ⅱ tool. The similarities and differences of the guidelines were analyzed and compared. RESULTS: A total of 7 pediatric ITP evidence-based guidelines were included, among which 2 came from US, 2 came from Italy, 2 came from British and another one came from Malaysia. The quality of 7 guidelines were not good, among which 6 guidelines were recommended as grade B and 1 guideline was recommended as grade C; only one GRADE evidence-based guideline was found. The score of included guideline in the field of AGREE Ⅱ was in descending order as scope and purpose, clarity, rigor of development, stakeholder involvement, applicability, editorial independence. The main recommended drugs of these guidelines were: glucocorticoids, intravenous immunoglobulin, anti-D-immunoglobulin, while some guidelines recommend platelet, rituximab and combined medication. CONCLUSIONS: The quality of evidence-based guidelines of ITP for children is in low level and should be improved. There is no evidence-based guideline of ITP for children in China. It is suggested to develop high quality evidence-based guideline for ITP children in China based on AGREE Ⅱ items.

Evidence-based Evaluation on the Current Status of Global Antibacterial Use Surveillance / 中国药房

OBJECTIVE:To provide evidence-based basis for the continuous improvement of antibacterial use surveillance in China.METHODS:Retrieving from 3 biomedical literature databases as Medline,Embase,Cochrane Library,48 health administrative departments and academic institutions,relevant literatures on antibacterial surveillance networks/ projects were acquired and extracted,including basic information,data collection,analysis and reporting methods,etc.Descriptive analysis method was adopted to analyze the status quo of global antibacterial surveillance networks/projects.RESULTS:A total of 21 literatures were included,involving 16 antibacterial surveillance networks/projects.Among them,there were 3 international projects and 13 national projects,mainly in European (countries) (56.25％,9/16).Sixteen antibacterial surveillance networks/projects were established to monitor and compare the use of antibacterials,analyze the antibacterial use trend and its correlation with bacterial resistance,and evaluate implementation effect of antibacterial management policy.The responsible agencies were mainly the health administrative departments,and the funding agencies were mainly related government departments.Hospital and community were main surveillance objects.There were 2 surveillance networks/projects for antibacterial use in children,and 6 surveillance networks/projects contained medication data of children.Only Strama in Sweden alone analyzed medication data in children.Fourteen surveillance networks/projects promulgated data collection methods or contents;data collection was mainly based on active reporting and involved the data of drug use/consumption and population/ patient.Except for ESAC-Net,ARPEC,NAUSP,data validation method was not mentioned in other surveillance networks/projects.Data analysis was most common in medical institutions and antibacterial categories,and defined daily dose was the most commonly used statistical indicators of antibacterial consumption.Ten surveillance networks/projects promulgated surveillance reports which were mostly published annually.CONCLUSIONS:Antibacterial surveillance have been widely operated worldwide.But there is a lack of monitoring and analysis of antibacterial use in special population including children.In addition,data validation is the weak link of antibacterial surveillance,so the quality of data collection still need to be improved.

Evidence-based Evaluation of Monitoring System for Global Short Drugs / 中国药房

OBJECTIVE:To systematically evaluate the monitoring system for global short drugs,and provide evidence-based reference and policy recommendations for developing the short drug monitoring in China. METHODS:Relevant literatures pub-lished in PubMed,Embase,CNKI,Wanfang,VIP database from building to Apr. 3rd in 2017 were retrieved by using"Drugs (cheap drugs,essential medicines,emergency drugs) storage""Short drugs""Insufficient supply of drugs""Drug shortage"as Chinese keywords,and"Drug storage""Out-of-stock drug""Stortage of medicine""Stock out of medicine"as English keywords. Literatures about monitoring system for short drugs in Baidu,Google and national or regional health administration websites were collected,and general information,data collection,data validation,data reporting method,feedback and improvement measures of monitoring system were extracted. RESULTS & CONCLUSIONS:Totally 25 literatures were included,20 national or regional health administration websites were retrieved. 11 countries and European Union had established monitoring system for short drugs. The main reporting agencies in each country were different,which were production enterprises,business enterprises and medical in-stitutions. It was mainly reported by network. Data validation was mainly conducted by specialized departments or groups for short drugs in each country. The monitoring reporting included information of short drugs and discontinued drugs. Countermeasures in each country mainly included looking for alternative drugs,encouraging production,temporary import,looking for new or other sources of raw materials and speeding up the approval of short drugs. Besides, precautions included implementation relevant laws and guidelines for short drugs,and increasing the cooper-ation with non-government departments,etc. Monitoring sys-tem for short drugs needs to be further improved in China. Itis suggested to establish monitoring and early warning platform for short drugs,and hierarchical intervention mechanism,improv-ing relevant laws and developing guidelines on managing short drugs.

"Access to Essential Medicine":Introduce of China's Proposal at the 67th World Health Assembly / 中国药房

OBJECTIVE:To provide reference for the proper understanding of the content of"Access to Essential Medicine"resolution proposed by China at the 67th World Health Assembly(WHA),policy making and implication of the resolution in Chi-na. METHODS:Through descriptive analysis,the proposal background,approving process and resolution content of the"Access to Essential Medicines"resolution were introduced;the potential impact and effect of the resolution were analyzed. RESULTS:"Ac-cess to Essential Medicine"included"urging member states"and"requesting director-general",20 items."Urging member states"covered 11 items,including national medicine policy,essential medicine selection,medicine related health systems research,inter-national exchanges and cooperation,children's essential medicine accessibility,essential medicine related education,training and public recognition,obstacle recognition and strategy development,essential medicine management system and monitoring mecha-nism,flexible use of the existing policy."Requesting director-general"covered 9 items and put forward the support WHO needed to realize"urging member states"and effect evaluation after the resolution. CONCLUSIONS:"Access to Essential Medicine"is great significance to maintain human health,especially people's health in developing countries,safeguard the rights and interests of peo-ple's basic drug use and promote rational drug use. The approval of"Access to Essential Medicine"at WHA represents China's in-ternational discourse right on improving the basic medical service among basic population,and highlights China's magnitude of a great nation.

Analysis of Global National Drug Policies on Rational Pediatric Drug Use / 中国药房

OBJECTIVE:To evaluate evidence situation and implementation of global national drug policies on rational pediatric drug use,and to provide decision-making reference for setting up national drug policies for rational pediatric drug use which adapt to the situation of China.METHODS:By retrieving domestic and foreign related database,scanning drug management websites of WHO,the European Union as well as many countries and regions.A pre-designed data extraction form was used to collect information of the policies of rational pediatric drug use.The information was summarized and analyzed.RESULTS:A total of 45 literatures were included,involving WHO and the European Union,the United States,Canada,Britain,Ireland,Holland,Germany,Spain,France,Australia,New Zealand,China,India,Korea,Japan,South Africa and many other countries and regions.The main points of concern for the national policies of rational pediatric drug use in all countries included promoting the development of clinical trials of children's drugs,formulating and promoting essential medicine list for children,formulating and promoting standard treatment guideline of national pediatric formulary,etc.,and promoting pediatric drug monitoring after the listing.The United States,the European Union and Japan had enacted national laws and regulations on pediatric drug clinical trials;WHO,South Africa and India had developed pediatric essential medicine list;WHO,Britain and China had established pediatric formulary.CONCLUSIONS:It is suggested that the relevant departments should refer to the experiences of the United States and the European Union and other countries and regions to establish national drug policies which adapt to pediatric disease burden and drug use in China

Meta-analysis of the Efficacy and Safety of Anti-vascular Endothelial Growth Factor Inhibitor in the Treat-ment of Retinopathy of Prematurity / 中国药房

OBJECTIVE:To systematically review the efficacy and safety of anti-vascular endothelial growth factor(VEGF)in-hibitors in the treatment of retinopathy of prematurity (ROP),and provide evidence-based reference for clinic. METHODS:Re-trieved from PubMed,EMBase,Cochrane Library,CJFD,VIP,CBM and Wangfang Database,randomized controlled trials (RCT) about VEGF inhibitors (test group) versus laser photocoagulation treatment (control group) in the treatment of ROP were collected. Meta-analysis was performed by using Rev Man 5.1 software after data extraction and quality evaluation by Cochrane re-viewers manual 5.1.0. RESULTS:Totally 5 RCTs were included,involving 381 infants and 754 eyes.Results of Meta-analysis showed that the recurrence rate of ROP [RR=0.23,95%CI(0.13,0.42),P0.05). CONCLUSIONS:Intravitreal VEGF inhibitors have better efficacy than laser photocoagulation in the treatment of ROP,but the optimal dose and safety need further verification by large-sam-ple and well-designed RCT.