简述临床监查员的工作职责和工作流程

1、1、 简述临床监查员的工作职责和工作流程。1） 临床监查员的工作职责：广义的来说，是从事临床试验组织工作的一个行业，也就是说，在临床试验进行的过程中，申办者通过监查员对试验中心进行定期访视，以保证试验受试者的权益及隐私。同时确保试验按照GCP、试验方案、标准操作程序及现行管理法规法律正确执行。从一个项目，从拿到国家的临床批件开始，到整理出临床试验所必须的资料上交给注册部门，这中间的所有环节，都是一个监查员所需要涉及的，包括基地和研究者的筛选，费用的调研，方案草案的制定，试验具体的实施过程中所牵涉的一系列问题，试验结果材料的整理，等等。狭义上的临床监查员的工作一般是负责上面所说的那些环节中间的一

2、部分，而其中最核心的是去医院检查项目的执行情况，包括资料的完整性，内容真实性，时间的逻辑性，医生的合作性等，发现试验中所存在的各种不同的问题，包括坏的问题比如不良反应、好的问题比如新的适应症等。2）临床监查员工作内容和程序整理CRA主要有以下的工作：1、确定试验方案，负责与总部沟通；2、临床试验的质量控制（通过co-monitoring、SDV等方式）；3、促进入组速度；4、收集新的试验信息。5、数据、文件分析。 CRA具体工作如下：工作序号工作项目主要工作内容临床试验启动阶段1制定临床研究计划在临床试验启动前，临床监查员应制定科学、可行、全面而详细的临床研究计划。包括：临床进度总体时间安排；

3、临床启动计划；临床监查计划；临床统计计划；临床总结计划；临床费用预算；可能出现的问题及解决方法。2准备研究者手册通过查阅相关专业文献资料，临床监查员负责编写研究者手册。主要内容包括：背景资料；化学资料；药学资料；药理毒理学资料；临床及对照药相关资料、相关文献等。3选择临床单位（包括牵头单位）拜访拟定各临床单位，并考察其：合作态度、团队精神；人员资格、数量、工作经验；试验场所、床位；临床试验检查仪器和设备；日门诊量等。在充分考察上述条件的基础上，选定牵头和临床参加单位。4选择统计单位通过多种渠道详细了解并核实：统计单位资质条件（专业基础及人员配备组成等）；合作态度；工作效率；工作程序等。在充分考

4、察上述条件的基础上，选定临床统计单位。5起草临床方案并设计CRF表监查员独立或会同主要研究者拟定临床方案（草案）；监查员根据临床方案设计CRF表（草案）。6召开临床协调会与各临床中心协商确定临床协调会召开时间和地点；拟定会议工作安排及分工；准备临床协调会相关资料（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相关问题。7修订临床方案及CRF表根据临床协调会意见，由监查员负责修订临床方案及CRF表，并经主要研究者同意后确定。8申请伦理委员会通过准备伦理委员会开会资料，包括：临床研究批件；临床研究方案；CRF表；临床研究者手册；知情同意书样本；临床样品检验报告单。将上述资

5、料整理并提交牵头医院伦理委员会，同时缴纳一定伦理委员会咨询费用，即可申请伦理委员召开会议并讨论通过。9SFDA备案准备以下相关备案资料：临床研究方案；临床研究参加机构名称及研究者姓名；伦理委员会审核同意书；知情同意书样本。将上述资料整理齐备后，提交国药局及各临床单位所在地省级药监局备案。10签订临床研究协议监查员起草与各临床中心研究协议，并经公司和医院双方同意后签订协议。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准备临床样品根据临床试验类型（随机或双盲等）计划临床样品数量和包装形式；做计划购买对照药品；设计各种规格临床研究用样品标签；设计各种大小临床样

6、品包装盒；协助统计专家编制随机表；协助统计专家对临床样品编盲；填写盲底交接记录表。13发放临床样品将临床药品发放各临床中心并填写交接记录；同时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，对其进行相关药政法规及临床方案和CRF表知识培训；对各临床中心提出的问题进行答疑。15获得各中心临床检测正常值范围对所有临床研究中涉及的临床实验室检查均要取得各中心正常值范围；对各中心不同正常值范围进行调查核实；将此正常值范围表提交临床统计单位。16拟定招募受试者广告如采用，则监查员应负责起草及处理张贴招募受试者广告相关事宜。临床试验进行阶段17制定访视计划制

7、定访视时间表；制定CRF表收集计划；将上述计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试验方案的执行情况；确认在试验前取得所有受试者的知情同意书；了解受试者的入选率及试验的进展状况；确认入选的受试者合格；确认所有数据的记录与报告正确完整，所有病例报告表填写正确，并与原始资料一致；所有错误或遗漏均已改正或注明，经研究者签名并注明日期；确认每一受试者的剂量改变、治疗变更、合并用药、伴发疾病、失访、检查遗漏等均确认并记录；确认入选受试者的退出与失访均已在病例报告表中予以说明；确认所有不良事件均记录在案，严重不良事件在规定时间内作出报告并记录在案；核实试验用药品按照有关法规进行供应、储藏

8、、分发、收回，并做相应的记录；协助研究者进行必要的通知及申请事宜；监查并如实记录研究者未能做到的随访、未进行的试验、未做的检查，以及是否对错误、遗漏作出纠正；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、监查的发现等，并存档。19进度调节根据不同医院进度，经相应临床中心同意后适当进行病例调节。20中期或年度临床进度报告根据临床进度情况，向SFDA报告中期或年度临床进度情况。临床试验总结阶段21回收CRF表 监查员回收CRF表，并做专业和技术审核。 22揭盲 监查员会同主要研究者、统计专家共同揭盲，并填写揭盲记录。23编写统计计划书监查员独立或与主要研究者一起

9、共同编写总结大纲；同统计专家一起，根据临床试验目的和总结大纲，编写并审核临床统计计划书。24数据录入统计专家建立数据库；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 统计专家编写统计运算程序。26统计运行统计程序，监查员应对出现的问题协同解决；对统计检验发现的问题，监查员负责协同研究者进行答疑。27统计报告统计专家出具统计报告；监查员负责对统计报告进行审核并提出具体意见。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；临床总结最终由研究者审核并确定。29临床总结会根据需要，临床监查员召集各临床中心研究者和统计专家召开临床总结会；会议程序同临床协调会。30申报

10、资料完成监查员负责将最终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。临床试验结束后31向伦理委员会报告向伦理委员会报告试验结束函；试验结束后的严重不良事件报告32试验用药销毁详细记录试验用药品的回收、存放；详细记录临床药品的销毁方法及经过。33文件存档临床试验中所有文件均需按GCP要求存档，并指定专人负责。其他工作34制定标准操作规程（SOP） 临床研究每项工作均需制定标准而详细的书面规程，即标准操作规程（SOP）。35文档管理严格遵循“Norecord，Noaction“之原则，对临床中涉及的每项工作均进行文件归档管理，并按照GCP要求存放。36学习与培训药政法规学习

11、；专业学习（医学、药学、统计学等）；每个项目临床启动前，临床监查员均需要对该项目涉及的各项知识进行学习、培训，并经过考核合格后方可进行该项目的临床监查。2、盐酸阿比朵尔（Arbidol）制剂已在我国上市，请查询阿比朵尔在抗病毒方面的药效学和临床试验的相关资料（主要为英文资料）。l Sensitivity of various influenza virus strains to arbidol. Influence of arbidol combination with different antiviral drugs on reproduction of influenza virus A

12、Leneva IA, Fediakina IT, Guskova 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 influ

13、enza 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

14、 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 patho

15、genic 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 ribam

16、idil. 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 compli

17、cations in servicemenShuster AM, Shumilov VI, Shevtsov VA, Marin 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 tim

18、e. 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 didnt take arbidol the minimal threshold of influenza and other acute respiratory viral infections incidence

19、 (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 didnt change.l Efficacy and safety of arbidol in treatment of naturally acquir

20、ed influenzaWang 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. METH

21、ODS: 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 i

22、n 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

23、 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 PP

24、i 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

25、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 sim

26、ilar 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 Triall Arbidol hydrochloride Pharmacodynamic study of ant

27、i-influenza virus infectionSun Yan-chi, ZHANG Shu-qin LIU Zhi-yi Liu Jianwei JinyuqinStudy about pharmacodynamics of arbidol hydrochloride on Influenza virus infectionAbstract Objective : To investigate the effects of the anti-influenza virus Arbidol role. Methods vivo, in vitro model of influenza v

28、irus. 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

29、 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 word

30、s : School OfficAuthor : Jinyuqin (1979-), female, masters degree students, research direction : virology; Sun - (1958-) male, masters, professors and research directions : virology, communications authors Tel Fax : E-mail : The goal : Jinyuqin (Rege

31、nerative 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, Changch

32、un 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

33、, 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, 2000,11 (2) : 81-5. 2Gushkov RG, Gus Kovacevic TA, Krylova. Nikolaeva IS.Mechanisms of arbid-ole s immunomodulating actio

34、nJ. Vestn Ross Akad Med Nauk. 1999, (3) : 36-40. 3Drinevskii VP, Osidak LV. Natsina VK et al.Chemotherapeutics for treatment of Influenza and other viral respiratory tractinfaction in child-renJ. AntibiotKhimioter. 1998,43 (9) : 29-34. 4Shumilov VI, Shuster AI. Lobastov SP et al.Efficiency of arbido

35、l in prophylaxic and treatment of respiratory viral infections in servicementJ acut. Voen MedZh. 2002,323 (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 cl

36、inical virology M, Beijing : Peoples Medical Publishing House. 1991:563. Received Date : January 12, 2004 Xiu draft Date : March 3, 2004 Publication date : October 20, 2004l Efficacy of arbidol in prophylaxis and treatment of acute respiratory viral infections in servicemenShumilov VI, Shuster AM, L

37、obastov 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 effe

38、ctiveness 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

39、 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 per

40、mitted to decrease the febrile period, to reduce the manifestation of symptoms of intoxication and affection of upper respiratory tract. Clinical TrialREPORT on the program of the estimation of the effectiveness of the medicine of Arbidol in the preventive maintenance and the treatment of influenza

41、and sharp respiratory virus infections in soldiers.Moscow 2002The 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, par

42、ts 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 t

43、he 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 i

44、n 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 expenditu

45、res, connected with the acute respiratory diseases in soldiers. l Approaches and strategies for the treatment of influenza virus infectionsJoseph M Colacino, Kirk A Staschke, and W Graeme LaverInfluenza A and B viruses belong to the Orthomyxoviridae family of viruses. These viruses are responsible f

46、or 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 t

47、o 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

48、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 c

49、omplex 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 clinic

50、al trials or been considered for their clinical utility will be mentioned.REPORT Arbidol in the preventive maintenance of the influenza and other sharp respiratory virus infections in children at the age is older than 6 years.Sharp respiratory infections relate to the number of most extended disease

51、s of man and compose half or more from the total number of acute diseases (Pilar Orine F.J. and co-auth., 1998). As early as 1979 by the World Health Organization (WHO - WORLD HEALTH ORGANIZATION) it was recomended to the scientific research associations focus first priority attention on the develop

52、ment of the effective methods of preventive maintenance and timely diagnostics of respiratory pathology in children. After practically quarter of century the problem of respiratory infections in children became even more urgent. The diseases of the organs of respiration - most frequent pathology in

53、children (Kagans S.YU. and co-auth., 1998), which specifies the expediency to isolate sharp respiratory infections into the separate group of the diseases of respiratory system. The results of epidemiological studies attest to the fact that on the average each child transfers from 3 to 5 episodes OR

54、Z per year (Korovin N.A. and co-auth., 1998). Obtained data clinically base the expediency of using Arbidol with the therapeutic and prophylactic purpose in the categories of children being investigated and are the basis of the guarantee of a data base for further estimated studies in the real pract

55、ice.3、右美沙芬已在国内上市多年，请设计一个观察右美沙芬冶疗咳嗽的临床试验草案，此方案应包括病例入选标准、排除标准、疗效指标、安全性评价指标等。右美沙芬治疗咳嗽的安全性和有效性的随机、双盲、阳性药平行对照、多中心临床再评价研究。临床研究组长单位：临床研究负责人：临床研究参加单位：申报单位：试验负责人：一、 研究题目右美沙芬治疗咳嗽疗效和安全性的多中心、随机双盲、平行对照临床试验二、 研究背景三、 研究目的：考察右美沙芬临床止咳的有效性和安全性。四、 申报单位和研究单位申报单位：地址：试验负责人：临床监查员：临床研究组长单位：地址：试验负责人： 电话： E-mail：参加单位：XXXXXXX

56、X 试验负责人：XXX XXXXXXXX 试验负责人：XXX五、 试验设计：采用多中心，随机双盲、平行对照试验设计。六、 病例选择(一) 入选标准：1. 年龄在18-60岁之间，男女比例适中；2. 临床确诊为有单纯性咳嗽痰少症状者；3. 经实验室检查无严重的心、肝、肾等主要脏器或造血系统疾病，肝肾功能正常的患者；4. 同意参加本试验并签署书面知情同意书者。(二) 排除标准1. 本研究开始前3月内曾参加过其他临床试验；2. 咳嗽伴痰多、哮喘患者；对右美沙芬过敏者；3. 肝肾功能异常，心功能不全，脑部疾患，血液系统疾病者；有精神病史者；4. 药物及/或酒精滥用；5. 孕妇或哺乳期妇女6. 依从性差，不能完成疗程者；7. 其他。（三）病例剔除标准1. 受试期间未按方案用药，无法判定疗效者。2. 受试期间因发生不良反应被迫中断治疗者，不做临床疗效统计，但要纳入不良反应病例统计分析。3. 病例依从性较差者；4. 研究人员认为需退出试验的任何情况。所有退出病例，应真实记录备查，并需进行安全性分析，试验结束时统计脱落率，并分析其原因，尽可能将脱落率