简述临床监查员的工作职责和工作作业流程.doc

1、 简述临床监查员工作职责和工作流程。
1） 临床监查员工作职责：
广义来说，是从事临床实验组织工作一种行业，也就是说，在临床实验进行过程中，申办者通过监查员对实验中心进行定期访视，以保证明验受试者权益及隐私。同步保证明验按照GCP、实验方案、原则操作程序及现行管理法规法律对的执行。从一种项目，从拿到国家临床批件开始，到整顿出临床实验所必要资料上交给注册部门，这中间所有环节，都是一种监查员所需要涉及，涉及基地和研究者筛选，费用调研，方案草案制定，实验详细实行过程中所牵涉一系列问题，实验成果材料整顿，等等。
狭义上临床监查员工作普通是负责上面所说那些环节中间一某些，而其中最核心是去医院检查项目执行状况，涉及资料完整性，内容真实性，时间逻辑性，医生合伙性等，发现实验中所存在各种不同问题，涉及坏问题例如不良反映、好问题例如新适应症等。
2）临床监查员工作内容和程序整顿
CRA重要有如下工作：
1、拟定实验方案，负责与总部沟通；
2、临床实验质量控制（通过co-monitoring、SDV等方式）；
3、增进入组速度；
4、收集新实验信息。
5、数据、文献分析。
CRA详细工作如下：
工作序号
工作项目
重要工作内容
临床实验启动阶段
1
制定临床
研究筹划
在临床实验启动前，临床监查员应制定科学、可行、全面而详细临床研究筹划。涉及：临床进度总体时间安排；临床启动筹划； 临床监查筹划； 临床记录筹划；临床总结筹划；临床费用预算； 也许浮现问题及解决办法。
2
准备研究
者手册
通过查阅有关专业文献资料，临床监查员负责编写研究者手册。重要内容涉及：背景资料；化学资料；药学资料； 药理毒理学资料；临床及对照药有关资料、有关文献等。
3
选取临床单位（涉及牵头单位）
拜访拟定各临床单位，并考察其：合伙态度、团队精神；人员资格、数量、工作经验；实验场合、床位；临床实验检查仪器和设备；日门诊量等。在充分考察上述条件基本上，选定牵头和临床参加单位。
4
选取记录单位
通过各种渠道详细理解并核算：记录单位资质条件（专业基本及人员配备构成等）；合伙态度；工作效率；工作程序等。在充分考察上述条件基本上，选定临床记录单位。
5
起草临床方案并设计CRF表
 监查员独立或会同重要研究者拟定临床方案（草案）； 监查员依照临床方案设计CRF表（草案）。
6
召开临床协调会
与各临床中心协商拟定临床协调会召开时间和地点；拟定会议工作安排及分工；准备临床协调会有关资料（技术资料、会议签到表、准备研究者签名样张等）；召开协调会并讨论临床方案及有关问题。
7
修订临床方案及CRF表
依照临床协调会意见，由监查员负责修订临床方案及CRF表，并经重要研究者批准后拟定。
8
申请伦理委员会通过
准备伦理委员会开会资料，涉及：临床研究批件；临床研究方案；CRF表；临床研究者手册；知情批准书样本； 临床样品检查报告单。　　将上述资料整顿并提交牵头医院伦理委员会，同步缴纳一定伦理委员会征询费用，即可申请伦理委员召开会议并讨论通过。
9
SFDA备案
准备如下有关备案资料： 临床研究方案；临床研究参加机构名称及研究者姓名；伦理委员会审核批准书；知情批准书样本。将上述资料整顿齐备后，提交国药局及各临床单位所在地省级药监局备案。
10
订立临床研究合同
监查员起草与各临床中心研究合同，并经公司和医院双方批准后订立合同。
11
印制正式CRF表
临床监查员同印刷厂家一起印制并校对正式三联无炭复写CRF表。
12
准备临床样品
依照临床实验类型（随机或双盲等）筹划临床样品数量和包装形式；做筹划购买对照药物；设计各种规格临床研究用样品标签；设计各种大小临床样品包装盒；协助记录专家编制随机表；协助记录专家对临床样品编盲；填写盲底交接登记表。
13

发放临床样品
将临床药物发放各临床中心并填写交接记录；同步发放临床研究者手册、临床方案、正式CRF表。
14
对研究者进行培训
监查员分别召集各临床中心研究者，对其进行有关药政法规及临床方案和CRF表知识培训； 对各临床中心提出问题进行答疑。
15
获得各中心临床检测正常值范畴
 对所有临床研究中涉及临床实验室检查均要获得各中心正常值范畴；对各中心不同正常值范畴进行调查核算；将此正常值范畴表提交临床记录单位。
16
拟定招募受试者广告
如采用，则监查员应负责起草及解决张贴招募受试者广告有关事宜。
临床实验进行阶段
17
制定访视筹划
 制定访视时间表；制定CRF表收集筹划；将上述筹划明确告知各临床中心。

18

临床质量控制
监查员监查研究者对实验方案执行状况；确认在实验前获得所有受试者知情批准书；理解受试者入选率及实验进展状况；确认入选受试者合格；确认所有数据记录与报告对的完整，所有病例报告表填写对的，并与原始资料一致；所有错误或漏掉均已改正或注明，经研究者签名并注明日期；确认每一受试者剂量变化、治疗变更、合并用药、伴发疾病、失访、检查漏掉等均确认并记录；确认入选受试者退出与失访均已在病例报告表中予以阐明；确认所有不良事件均记录在案，严重不良事件在规定期间内作出报告并记录在案；核算实验用药物按照关于法规进行供应、储藏、分发、收回，并做相应记录；协助研究者进行必要告知及申请事宜；监查并如实记录研究者未能做到随访、未进行实验、未做检查，以及与否对错误、漏掉作出纠正；
监查员每次访视后均要作一书面报告递送研究者，报告应述明监查日期、时间、监查员姓名、监查发现等，并存档。
19
进度调节
依照不同医院进度，经相应临床中心批准后恰当进行病例调节。
20
中期或年度临床进度报告
依照临床进度状况，向SFDA报告中期或年度临床进度状况。
临床实验总结阶段
21
回收CRF表
    监查员回收CRF表，并做专业和技术审核。
22
揭盲
    监查员会同重要研究者、记录专家共同揭盲，并填写揭盲记录。
23
编写记录筹划书
监查员独立或与重要研究者一起共同编写总结大纲；同记录专家一起，依照临床实验目和总结大纲，编写并审核临床记录筹划书。
24
数据录入
记录专家建立数据库；监查员对数据库进行审核；监查员协同并监查数据录入。
25
编写程序
    记录专家编写记录运算程序。
26
记录
运营记录程序，监查员应对浮现问题协同解决；对记录检查发现问题，监查员负责协同研究者进行答疑。
27
记录报告
记录专家出具记录报告；监查员负责对记录报告进行审核并提出详细意见。
28
起草临床大总结和分总结
临床监查员独立或协同研究者起草临床总结；临床总结最后由研究者审核并拟定。
29
临床总结会
依照需要，临床监查员召集各临床中心研究者和记录专家召开临床总结会；会议程序同临床协调会。
30
申报资料完毕
监查员负责将最后定稿临床总结打印校对完毕并装订成上报材料；将定稿临床总结送交注册组。
临床实验结束后
31
向伦理委员会报告
向伦理委员会报告实验结束函；实验结束后严重不良事件报告
32
实验用药销毁
详细记录实验用药物回收、存储；详细记录临床药物销毁办法及通过。
33
文献存档
临床实验中所有文献均需按GCP规定存档，并指定专人负责。
其她工作
34
制定原则操作规程（SOP）
    临床研究每项工作均需制定原则而详细书面规程，即原则操作规程（SOP）。
35
文档管理
严格遵循“No  record，No  action“之原则，对临床中涉及每项工作均进行文献归档管理，并按照GCP规定存储。
36
学习与培训
药政法规学习；专业学习（医学、药学、记录学等）；每个项目临床启动前，临床监查员均需要对该项目涉及各项知识进行学习、培训，并通过考核合格后方可进行该项目临床监查。

2、盐酸阿比朵尔（Arbidol）制剂已在国内上市，请查询阿比朵尔在抗病毒方面药效学和临床实验有关资料（重要为英文资料）。
l Sensitivity of various influenza virus strains to arbidol. Influence of arbidol combination with different antiviral drugs on reproduction of influenza virus A

Leneva IA，Fediakina IT，Gus'kova TA，Glushkov RG.

AIM：To study antiviral activity of arbidol in relation to various antigenic subtypes of influenza virus isolated from humans；efficacy of arbidol action in combination with adamantanic antiviral drugs，ribavirin and ribamidil on reproduction of influenza virus A (IVA) in cell culture. MATERIAL AND METHODS：The activity of the drugs against viral reproduction was assessed by inhibition of viral antigens expression detected in virus-infected cells using enzyme immunoassay (EIA). RESULTS：Arbidol is just as good as adamantanic drugs，neuraminidase inhibitors，ribavirin and ribamidil by its inhibiting activity in relation to influenza viruses A and B. Arbidol inhibits reproduction of human IVA antigenic strains H1N1，H2N2，H3N2 and remantadin-sensitive and remantadin-resistant strains of influenza virus. Arbidol inhibits reproduction of pathogenic for humans strains of avian influenza virus H5N1 and H9N2，strains H6N1 and H9N2 having internal genes common with H5N1 and H9N2. The inhibiting activity of arbidolin on cell culture viral reproduction enhanced if arbidol was used in combination with amantadine，remantadin，ribavirin and ribamidil. CONCLUSION：Arbidol has a wide spectrum antiviral activity and inhibits reproduction of various antigenic subtypes and remantadin-resistent human IVA，avian viruses H5N1 and H9N2，influenza viruses B and C.

l Arbidol used in the prophylaxis of acute respiratory viral infections and their complications in servicemen

Shuster AM，Shumilov VI，Shevtsov VA，Mar'in GG，Kozlov VN.

The prophylactic action of arbidol to prevent the acute respiratory viral infections and their complications (extra-hospital pneumonia) was studied under conditions of two military collectives during winter and summer time. The data obtained confirm the prophylactic activity of the drug in respect of acute respiratory viral infections. Regardless of the degree of disease epidemic rise among the servicemen who didn't take arbidol the minimal threshold of influenza and other acute respiratory viral infections incidence (10-15%) remained in the experimental group. The incidence of pneumonia decreased. It was connected with decrease in viral-and-bacterial pneumonia. The number of patients with bacterial (generally pneumococcal) pneumonia didn't change.

l Efficacy and safety of arbidol in treatment of naturally acquired influenza

Wang MZ，Cai BQ，Li LY，Lin JT，Su N，Yu HX，Gao H，Zhao JZ，Liu L.

Department of Respiratory Disease，PUMC Hospital，CAMS and PUMC，Beijing 100730，China.

OBJECTIVE：To evaluate the efficacy and safety of Arbidol in the treatment of naturally acquired influenza. METHODS：A randomized，double-blinded，placebo controlled trial was conducted. Subjects were enrolled. The inclusion criteria included：aged 18 to 65 years，presented within 36 hours of onset of influenza symptoms；and had documented temperature of 37.8 degrees C or higher during an influenza outbreak in the community. Individuals were randomly divided Arbidol group (200 mg three times daily for 5 days) or placebo group.

RESULTS：Totally 232 individuals were recruited and received medication and follow-up. All of them were qualified to be analyzed for safety as intent-to-treat population (ITT) (113 Arbidol，109 placebo). Twenty-two (9.48%) were during follow-up or refused to continue the trial，and 210 completed as scheduled and identified as PP population (102 Arbidol，108 placebo). Totally 125 individuals were identified as influenza-infected through laboratory test，which was defined as PPi population (59 Arbidol，66 placebo). In PPi population，the cumulative alleviation proportion of Arbidol group was significantly higher than that of placebo group. The median duration of illness was 72.0 hours (95% confident interval (CI) 66.00-78.00 hours) in Arbidol group and 96.0 hours (95% CI 87.46-104.54 hours) in placebo group. The median area under the curve (AUC) of decreased total score were significantly higher in Arbidol group than in placebo group，which were 780.00 and 684.00 score-hours respectively. For PP population，similar results were seen. Adverse events reported were similar in Arbidol group and in placebo group. The main adverse events were gastrointestinal symptoms and increased transaminase.

CONCLUSION：Arbidol was effective and well tolerated in the treatment of early naturally acquired influenza.
Clinical Trial

l Arbidol hydrochloride Pharmacodynamic study of anti-influenza virus infection

Sun Yan-chi，ZHANG Shu-qin LIU Zhi-yi Liu Jianwei Jinyuqin

Study about pharmacodynamics of arbidol hydrochloride on Influenza virus infection

Abstract Objective ：To investigate the effects of the anti-influenza virus Arbidol role. Methods vivo，in vitro model of influenza virus. Application for a certain concentration of hydrochloric acid in vitro Arbidol role in the influenza A virus subtype H1N1 infection of host cells. To investigate the use of CPE and the cell viability was measured by MTT assay；hydrochloric acid in vivo application for the treatment of influenza virus infection in mice Arbidol model Index changes in the lung. Arbidol hydrochloride results in vivo，In vitro anti-influenza viruses have the same effect. Conclusion Arbidol hydrochloride is a good anti-virus drugs.

Keywords ：Arbidol hydrochloride；The influenza virus；Pharmacodynamics "Key words ：School Offic

Author ：Jinyuqin (1979-)，female，master's degree students，research direction ：virology；Sun - (1958-) male，master's，professors and research directions ：virology，communications authors Tel:，Fax ：，E-mail ： The goal ：Jinyuqin (Regenerative Medicine Institute of Science Laboratory at Jilin University，Jilin，Changchun 130021) Sun - (Regenerative Medicine Institute of Science Laboratory at Jilin University，Jilin，Changchun 130021) Shuqin (Regenerative Medicine Institute of Science Laboratory at Jilin University，Jilin，Changchun 130021) Shu-qin LIU Zhi-yi (Regenerative Medicine Institute of Science Laboratory at Jilin University，Jilin，Changchun 130021) Liu Jianwei (Regenerative Medicine Institute of Science Laboratory at Jilin University，Jilin，Changchun 130021) Yan Qi (Changchun College of Respiratory Medicine，Jilin，Changchun 130021)

References ：
[1] Zhong Bin，Wang Sheng，，Sun et al. influenza in Thailand have anti-influenza virus activity of mouse model et al. Biotechnology Communications，,11 (2) ：81-5.
[2]Gushkov RG，Gus Kovacevic TA，Krylova. Nikolaeva IS.Mechanisms of arbid-ole 's immunomodulating action[J]. Vestn Ross Akad Med Nauk. 1999，(3) ：36-40.
[3]Drinevskii VP，Osidak LV. Natsina VK et al.Chemotherapeutics for treatment of Influenza and other viral respiratory tractinfaction in child-ren[J]. AntibiotKhimioter. 1998,43 (9) ：29-34.
[4]Shumilov VI，Shuster AI. Lobastov SP et al.Efficiency of arbidol in prophylaxic and treatment of respiratory viral infections in servicement[J] acut. Voen MedZh. ,323 (9) ：51-3,96.
[5] Wen-dong. Cell proliferation was measured by a colorimetric method，and quickly decay et al. The chemistry of life，1994,14 (6) ：44-6.
[Du Ping Zhu Guan，editor et al. Modern clinical virology [M]，Beijing ：People's Medical Publishing House. 1991:563.
Received Date ：January 12，
Xiu draft Date ：March 3，
Publication date ：October 20，

l Efficacy of arbidol in prophylaxis and treatment of acute respiratory viral infections in servicemen

Shumilov VI，Shuster AM，Lobastov SP，Shevtsov VA，Mednikov BL，Piiavskii SA，Litus VI.

The authors present the results of study of arbidolum therapeutic-and-prophylactic effectiveness in acute respiratory viral infections (ARVI) under conditions of military staff with determination of economic expediency. Coefficient of effectiveness of arbidolum prophylactic use was 25% and efficiency index--1.33. In experimental group the ARVI complicated forms were noted in 3% of the patients and in control group--in 5%. Due to decreased expenses on the treatment of non-complicated and complicated ARVI forms the cost of therapy of one servicemen in the first group was 290.6 rubles，in the second group--323 rubles，in the third group--336 rubles and in the fourth group--368 rubles. The results of investigation have shown the significant advantage of arbidolum therapeutic-and-prophylactic use compared with other variants. Its use permitted to decrease the febrile period，to reduce the manifestation of symptoms of intoxication and affection of upper respiratory tract.
Clinical Trial

REPORT on the program of the estimation of the effectiveness of the medicine of "Arbidol" in the preventive maintenance and the treatment of influenza and sharp respiratory virus infections in soldiers.

Moscow

The problem of acute respiratory diseases for the military associations with the high risk of the development of the infections of the respiratory tract is especially urgent. In particular，in the newly formed parts，training centers，parts from the composition of united groupings of troops in the local military conflicts and the peacemaking forces. Under the contemporary conditions respiratory diseases are predominantly the infections of those organized associations，where the conditions determine the activity of the mechanism of the transfer of agents and the heterogeneity of the composition of people. As the starting gear of the making more active of epidemic process with ORZ in the military associations serves their renovation. As proof serve lifts in the annual dynamics of morbidity connected with the calls in VS RF.

Use in the real practice of the developed positions on an improvement in the quality of preventive maintenance and treatment of sharp respiratory infections with the use of arbidol makes it possible to decrease morbidity，to increase the effectiveness of therapeutic measures and to optimize the expenditures，connected with the acute respiratory diseases in soldiers.

l Approaches and strategies for the treatment of influenza virus infections

Joseph M Colacino，Kirk A Staschke，and W Graeme Laver

Influenza A and B viruses belong to the Orthomyxoviridae family of viruses. These viruses are responsible for severe morbidity and significant excess mortality each year. Infection with influenza viruses usually leads to respiratory involvement and can result in pneumonia and secondary bacterial infections. Vaccine approaches to the prophy-laxis of influenza virus infections have been problematic owing to the ability of these viruses to undergo antigenic shift by exchanging genomic segments or by undergoing antigenic drift，consisting of point mutations in the haemagglutinin (HA) and neuraminidase (NA) genes as a result of an error-prone viral polymerase. Historically，antiviral approaches for the therapy of both influenza A and B viruses have been largely unsuccessful until the elucidation of the X-ray crystallographic structure of the viral NA，which has permitted structure-based drug design of inhibitors of this enzyme. In addition，recent advances in the elucidation of the structure and complex function of influenza HA have resulted in the discovery of a number of diverse compounds that target this viral protein. This review article will focus largely on newer antiviral agents including those that inhibit the influenza virus NA and HA. Other novel approaches that have entered clinical trials or been considered for their clinical utility will be mentioned.
REPORT "Arbidol in the preventive mainten