SOP_24-Clinical Data Management, Paper or Electronic Format-Procedures
Title Clinical Data Management, Paper or Electronic FormatCode SOP-24Pages 8History of Validated VersionsDateVersion Pages Description of Change dd/mm/yyyyHistory of SOP ImplementationVersion Datedd/mm/yyyydd/mm/yyyy Version Datedd/mm/yyyy Version DateApproval of Site SOPSignature Datedd/mm/yyyyTable of Contents1. Policy2. Objectives3. SiteResponsibilities3.1. Research Centre Director3.2. Sponsor-Investigator or Investigator / Qualified Investigator3.3. Person Responsible for the Site SOPs4. Procedures4.1. Generalities4.2. Confidentiality and Direct Access to Clinical Data4.3. Collection and Capture of Clinical Data4.4.Quality Control and Modifications to Clinical Data4.5.Processing of Clinical Data4.6. Storage of Clinical Data5.References6. AppendixAppendix 1 – Site Specific Instructions1. PolicyWithin the framework of the principles inherent in Good Clinical Practice (GCP) of the International Conference on Harmonisation (ICH) and those adhered to by Health Canada, as well as regulations of the FDA, this standard operating procedure (SOP) describes the management of clinical study data in terms of collection and entry into case report forms (CRFs), wether paper or electronic format.This SOP concerns all institutional personnel working in clinical research and should be adhered to by all personnel working on clinical studies involving human subjects.2. ObjectivesOne of the objectives of this operating procedure is to define the different stages of management of clinical data entered onto the CRFs, whether on paper or electronically.This SOP describes the stages of collection, capture and storage of data, as well as quality control and corrections to clinical data collected during the study.The other objective is to ensure that the collection, follow-up, control and confidentiality of all clinical data entered in a CRF, paper or electronic, conform to the principles of the ICHand the laws and regulations in force (to be completed). In order to achieve this goal, it is imperative that the system used for applicable capture and processing of data is validated, and that the databases in which clinical data are stored accurately represent the subject’s data.3. Site Responsibilities3.1 The Research Centre Director or his delegate is responsible for:3.1.1 Approving or updating site SOPs that will be used in the institution according tointernal institutional validation procedures;3.1.2 Informing members of the Ethics Committee that this site SOP will be implementedwithin the institution;3.1.3 Implementing and managing this site SOP within the institution;3.2 The Sponsor-Investigator or Investigator/Qualified Investigator is responsible for:3.2.1 Ensuring that, during the clinical study, the research team, which will be underhis/her supervision will comply with this site SOP.3.3 Under the supervision of the Research Centre Director or his delegate, the personresponsible for site SOPs should:3.3.1 At the time of implementation of each SOP ensure that clinical study personnel at theinstitution are trained in procedures and comply with this SOP.3.3.2 In the event that an SOP is modified, provide training for institutional clinical studypersonnel regarding the change(s) and ensure their compliance with any changes.4. Procedures4.1 GeneralitiesThe sponsor-investigator, who is responsible for the management of clinical data for the study, should:4.1.1In accordance with the ICH, employ appropriately qualified individuals to supervisethe overall conduct of the study, to handle and verify data, to conduct statisticalanalyses, and to prepare the study reports, ICH 5.5.1;4.1.2In the case where management of clinical data is performed directly by a servicewithin the institution, develop instructions according to the recommendations madeby the Society for Clinical Data Management (SCDM) and The Good Clinical DataManagement Practices;4.1.3Manage authorizations for access to clinical data within the clinical research unit,whether physical or electronic access to the clinical study data;4.1.4 Ensure the protection and security of clinical study data;4.1.5Ensure adherence to applicable regulatory requirements regarding confidentiality ofthe identity of subjects and their data by using unambiguous identification codes thatallows identification of all data reported for each subject, ICH 5.5.5;4.1.6 Precisely enter the data from the CRFs as required by the protocol. This data shouldcorrespond at every point with the data and source documents for all subjectsparticipating in the clinical study;4.1.7Ensure that the electronic system used for clinical data management is valid andcomplies with regulatory requirements, ICH 5.5.3a, FDA and MSSS;4.1.8Retain the original or a certified copy of the certified data backup as well as an audittrail, ICH 5.5.3.F and 5.5.4;4.1.9Ensure that clinical study reports are prepared and provided to regulatoryagency(ies) as required by the applicable regulatory requirement(s), ICH 5.22;4.1.10Ensure that a summary of the study results is provided to the ethics committee, ICH4.13;4.1.11Safeguard the blinding, if any (during data capture and processing), ICH5.5.3g.4.2. Confidentiality and Direct Access to Clinical Data4.2.1 A document identifying persons authorized to access, enter or correct clinical data inthe CRFs, should be retained with the essential study documentation, as describedin ICH-GCP, section 8.3 Essential Documents for the Conduct of a Clinical Trialpoint 8.3.24, and the document of the MSSS, Cadre global de gestion des actifsinformationnels - Volet sécurité, a. 4.1.2, par. 3.. Moreover, the MSSS documentstates that a control mechanism should be set up for tracking entry/exit of personsaccessing the site.4.2.2 This document should be updated according to the roles and responsibilitiesdelegated by the sponsor-investigator or the investigator/qualified investigator, asdescribed in SOP 03.4.3. Collection and Clinical Data Capture4.3.1All clinical study information should be recorded, processed, and stored in a waythat allows its accurate reporting, interpretation and verification, ICH 2.10.4.3.2In order to ensure the integrity and tracking of all clinical data, a procedure forcollecting, capturing, controlling, verifying, correcting and processing data should beestablished while respecting the fact that the study is blinded, if applicable, ICH5.5.3g .4.3.3Two methods can be used for the data capture: single or double data entry, this isdependant on type of CRF used and the location where it is carried out (site, CRO, etc). The method of capture is defined by the investigator or the sponsor-investigator in the protocol or other document.4.3.4 A system for tracking data entry and modification should be available for the periodof document retention according to the regulations in force.Paper CRFs:4.3.5Paper CRFs should be filled out according to SOP 25.Any modification made to theclinical data before capture should be justified and authorized by the investigator or his delegate. The process of modification should correspond to the procedure described in SOP 25. The CRF should be signed and dated by the investigator or his delegate, as described in the delegations/signatures document SOP 03 and in section 8.3 item 8.3.24 in ICH-GCP.4.3.6Data entry onto paper CRFs is carried out according to the method of double dataentry by two people. Comparison of the two entries and correction of errors can be made by a third person.4.3.7If clinical data is captured directly by the research team, only those authorized bythe investigator can then enter the CRF data into the database. This delegation of tasks will be documented, as described in SOP 03.4.3.8In the case where capture of clinical data is made by an external organization(CRO), as defined by the protocol, a copy of the CRF should retained by the investigator.Electronic CRFs:4.3.9Installation of an electronic system should be validated within the infrastructure ofthe clinical research unit, in order to ensure its reliability and precision, as well as its expected performance, ICH 5.5.3a. and FDA Guidance for Industry: Computerized System used in Clinical Trials.4.3.10 Only persons authorized by the sponsor-investigator or the investigator/qualifiedinvestigator and those who have an authenticated identification have access to the electronic data management system. Measures of protection, detection and correction should be in place (electronic signature or secure electronic signature).4.3.11In the case of online data entry, both methods of data entry are applicable.4.3.12 The sponsor-investigator or the investigator/qualified investigator should ensure thatthose using the clinical data processing system are trained in the use of the electronic system and follow the instructions described in Appendix 1 of SOP 02.4.3.13If, as stipulated in the protocol, clinical data are transferred to another system, thetransfer should be validated and secure.4.4 Quality Control and Modifications to Clinical Data4.4.1 In order to ensure the integrity of the data, the sponsor-investigator should establishquality control systems so that studies are conducted in accordance with theprotocol, with GCP and with the regulatory requirements.4.4.2 Quality control should be applied to each stage of data handling to ensure that alldata are reliable and have been processed correctly, ICH 5.1.3.4.4.3 In order to decrease errors during the data capture process (single or double),interactive quality controls can be established, whether it is for paper or electronicCRFs.4.4.4 In order to ensure coherence of the data within the same CRF, other quality controlsshould be applied once data capture is completed.4.4.5 Once the contents of a CRF are confirmed, all modifications made to the data byauthorized persons should be justified and documented.4.4.6 These modifications can be requested and documented on paper or electronicallyusing the Data Clarification Form (DCF), prepared by the research team or by theCRO in charge of data capture at the time the clinical study was initiated. Theseforms should be re-examined and signed by the investigator/qualified investigator orhis delegate. The original document should be retained by the sponsor/sponsor-investigator and a copy should be retained by the investigator/qualified investigator,ICH 8.3.15.4.4.7 A tracking system (paper or electronic) of all data modifications should be retainedfor 25 years in the case of clinical studies using an investigational product oraccording to the regulations in force for clinical studies without investigationproducts. This system should be accessible in the event of an audit and inspection.4.5 Clinical Data ProcessingProcessing of clinical data should be described in the protocol or in the statistical analysis plan.If the sponsor/sponsor-investigator uses electronic data processing systems at the site or at a remote site, he should ensure that the data processing is performed in accordance with study methodology such as blinding, if applicable, ICH 5.5.3 g4.5.1 The sponsor may consider establishing an independent data-monitoring committee(IDMC) to assess the progress of a clinical study, including safety data and thecritical efficacy endpoints at certain intervals, and to recommend to the sponsorwhether to continue, modify, or stop a study, ICH 5.5.2.4.5. The IDMC should have written operating procedures and maintain written records ofthe minutes of all their meetings, ICH 5.5.2.4.5.3 The sponsor-investigator can perform interim statistical analyses, while the study isbeing conducted, if so stipulated in the protocol.4.6 Storage of Clinical Data4.6.1 For any clinical study, the investigator/qualified investigator should ensure that theclinical data (paper or electronic) are protected against the effects of time andagainst all accidental destruction.4.6.2 In the case of a clinical study using a drug or medical device, paper or electronicCRFs, like all other source documents, should be retained for the necessary storageperiod required by Canadian regulations, C.05.012 (4), of 25 years.4.6.3 In the case of a clinical study without a drug or medical device, the period ofretention should comply with the schedule of storage of documents submitted by theinstitution to the provincial authorities. (Loi sur les archives. L.R.Q., chap. A-21.1 art.8, 9 and 35) (Recueil de règles de conservation des documents des établissementsde santé et services sociaux, section 4, dossier X1-0350, dossier de l’usager).4.6.4 The same period of document retention applies to the identification of thedocuments for archiving to, the recording of the information and to the assurancethat the archiving department has been informed that a medical file is related to aclinical study and that this file cannot be purged.5.ReferencesHealth Canada, Guidance for Industry, Good Clinical Practice: Consolidated guideline, ICH Topic E6, 1997.Food and Drug Administration (FDA), Electronic Records; Electronic Signatures Final Rule.21 CFR Part 11, Federal Register Vol. 62, No 54, March 20, 1997.Food and Drug Administration (FDA), Guidance for Industry: Computerized systems used in clinical trials, April 1999,Quebec, Archives Act (R.S.Q., A-21.1 a. 8, 9 and 35).Quebec, An act respecting access to documents held by public bodies and the protection of personal information (R.S.Q., A-2.1).Ministère de la santé et des services sociaux (MSSS), Cadre Global de Gestion des Actifs Informationnels appartenant aux organismes du réseau de la santé et des services sociaux : Volet Sécurité, septembre 2002.SCDM, Good Clinical Data Management Practices, Version 3, September 2003.SOP-02 Organizing a Site for Clinical Research.SOP-03Research Team: Role Definitions, Responsibilities and Task DelegationSOP-25 How to Fill In a Case Report Form and Modify DataSOP-26 Security and Confidentiality of DataAPPENDIX 1 INSTRUCTIONS SPECIFIC TO THE SITE (EXAMPLES)1. Filing System2. Location of Filing System3. Annual Approval or Revision4. Specific Responsibilities of the Institution5. Procedures6. References7. Appendices。
临床研究报告英文简称
临床试验相关名词及解释(中英文)1.临床试验（Clinical Trial）：指任何在人体（病人或健康志愿者身上）进行药品的系统性研究，以证实或揭示研究药品的作用、不良反应及／或试验用药品的吸收、分布、代谢和排泄，目的是确定研究药品的疗效与安全性。
2.试验方案（Protoco1）：叙述试验的背景、理论基础和目的，试验设计、方法和组织，包括统计学考虑、试验执行和完成的条件。
方案必须由参加试验的主要研究者、研究机构和申办者签章并注明日期。
3.研究者手册（Investigator's Brochure）：是有关试验用药品在进行人体研究时已有的临床与非临床资料。
4.知情同意（Informed Consent）：指向受试者告知一项试验的各个方面情况后，受试者自愿确认其同意参加该项临床试验的过程，须以签名和注明日期的知情同意书作为文件证明。
5.知情同意书（Informed Consent Form）：是每位受试者表示自愿参加某一试验的文件证明。
研究者必须向受试者说明试验性质、试验目的、可能的受益和危险、可供选用的其他治疗方法以及符合《赫尔辛基宣言》规定的受试者的权利和义务等，使受试者充分了解后表达其同意。
6.伦理委员会（Ethics Committee）：由医学专业人员、法律专家及非医务人员组成的独立组织，其职责为核查临床试验方案及附件是否合乎道德，并为之提供公众保证，确保受试者的安全、健康和权益受到保护。
该委员会的组成和一切活动不应受临床试验组织和实施者的干扰或影响。
7.研究者（Investigator)：实施临床试验并对临床试验的质量和受试者的安全和权益的负责者。
研究者必须经过资格审查，具有临床试验的专业特长、资格和能力。
在多中心临床试验中，由一名主要研究者对临床试验实施总负责，并作为各试验中心间的协调人。
8.协调研究者（Coordinating Investigator)：在多中心临床试验中负责协调各参加中心的研究者的工作的一名研究者。
国际药物注册标准词汇
国际药物注册英语词汇互译FDA（food and drug adminisration）：（美国）食品药品监督管理局NDA（new drug application）：新药申请ANDA（abbreviated new drug application）：简化新药申请EP（export application）：出口药申请（申请出口不被批准在美国销售的药品）treatment IND：研究中的新药用于治疗abbreviated（new）drug：简化申请的新药DMF（drug master file）：药物主文件（持有者为谨慎起见而准备的资料，可以包括一个或多个人用药物在制备、加工、包装和贮存过程中所涉及的设备、生产过程或物品。
只有在DMF持有者或授权代表以授权书的形式授权给FDA，FDA在审查IND、NDA、ANDA时才能参考其容）holder：DMF持有者CFR（code of federal regulation）：（美国）联邦法规PANEL：专家小组batch production：批量生产；分批生产batch production records：生产批号记录post or pre-market surveillance：销售前或销售后监督informed consent：知情同意（患者对治疗或受试者对医疗试验了解后表示同意接受治疗或试验）prescription drug：处方药OTC drug（over—the—counter drug）：非处方药U.S. public health service：美国卫生福利部NIH（national institute of health）：（美国）全国卫生研究所animal trail：动物试验accelerated approval：加速批准standard drug：标准药物investigator ：研究人员；调研人员preparing and submitting：起草和申报submission：申报；递交benefit(s)：受益risk（s）：受害drug product：药物产品drug substance：原料药established name：确定的名称generic name：非专利名称proprietary name：专有名称；INN（international nonproprietary name）：国际非专有名称narrative summary: 记叙体概要adverse effect：副作用adverse reaction：不良反应protocol：方案archival copy：存档用副本review copy：审查用副本official compendium：法定药典（主要指USP、 NF）．USP（the united state pharmacopeia）：美国药典（现已和NF合并一起出版）NF（national formulary）：（美国）国家药品集official＝pharmacopeial = compendial：药典的；法定的；官方的agency：审理部门（指FDA）sponsor：主办者（指负责并着手临床研究者）identity：真伪；鉴别；特性strength：规格；规格含量（每一剂量单位所含有效成分的量）labeled amount：标示量regulatory specification：质量管理规格标准（NDA提供）regulatory methodology：质量管理方法（FDA用于考核原料药或药物产品是否符合批准了的质量管理规格标准的整套步骤）regulatory methods validation：管理用分析方法的验证（FDA对NDA提供的方法进行验证）Dietary supplement：食用补充品ICH（International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use)人用药物注册技术要求国际协调会议 ICH：Quality-质量Q1A(R2): Stability Testing of New Drug Substances and Products (Second Revision)新原料药和制剂的稳定性试验（第二版）Q1B: Photostability Testing of New Drug Substances and Products 新原料药和制剂的光稳定性试验Q1C: Stability Testing for New Dosage Forms新制剂的稳定性试验Q1D: Bracketing and Matrixing Designs for Stability Testing of DrugSubstances and Drug Products原料药和制剂稳定性试验的交叉和矩阵设计Q1E: Evaluation of Stability Data对稳定性数据的评估处理Q1F: Stability Data Package for Registration Applications in ClimaticZones III and IV在气候带III和IV，药物注册申请所提供的稳定性数据Q2A: Text on Validation of Analytical Procedures分析程序的验证Q2B: Validation of Analytical Procedures: Methodology分析程序的验证：方法学Q3A(R): Impurities in New Drug Substances (Revised Guideline) 新原料药中的杂质（修订版）Q3B(R): Impurities in New Drug Products (Revised Guideline)新制剂中的杂质（修订版）Q3C: Impurities: Guideline for Residual Solvents杂质：残留溶剂指南Q3C(M): Impurities: Guideline for Residual Solvents (Maintenance) 杂质：残留溶剂指南（修改容）Q4: Pharmacopoeias药典Q4A: Pharmacopoeial Harmonisation 药典的协调Q4B: Regulatory Acceptance of Pharmacopoeial Interchangeability 药典互替在法规上的可接受性Q5A: Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin来源于人或者动物细胞系的生物技术产品的病毒安全性评估Q5B: Quality of Biotechnological Products: Analysis of the ExpressionConstruct in Cells Used for Production of r-DNA Derived Protein Products 生物技术产品的质量：源于重组DNA的蛋白质产品的生产中所用的细胞中的表达构建分析Q5C: Quality of Biotechnological Products: Stability Testing ofBiotechnological/Biological Products生物技术产品的质量：生物技术/生物产品的稳定性试验Q5D: Derivation and Characterisation of Cell Substrates Used forProduction of Biotechnological/Biological Products用于生产生物技术/生物产品的细胞底物的起源和特征描述Q5E: Comparability of Biotechnological/Biological Products Subject toChanges in Their Manufacturing Process基于不同生产工艺的生物技术产品/生物产品的可比较性Q6: Specifications for New Drug Substances and Products新原料药和制剂的质量规格Q6A: Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances质量规格：新原料药和新制剂的检验程序和可接收标准：化学物质Q6B: Specifications: Test Procedures and Acceptance Criteria forBiotechnological/Biological Products质量规格：生物技术/生物产品的检验程序和可接收标准Q7: Good Manufacturing Practices for Pharmaceutical Ingredients 活性药物成份的GMPQ7A: Good Manufacturing Practice Guide for Active PharmaceuticalIngredients活性药物成份的GMP指南Q8: Pharmaceutical Development药物研发Q9: Quality Risk Management质量风险管理ICH：Safety-安全S1A: Guideline on the Need for Carcinogenicity Studies of Pharmaceuticals 药物致癌性研究需要的指南S1B: Testing for Carcinogenicity of Pharmaceuticals药物致癌性的检验S1C: Dose Selection for Carcinogenicity Studies of Pharmaceuticals 药物致癌性研究之剂量选择S1C(R): Addendum: Addition of a Limit Dose and Related Notes 附录：极限剂量和有关注释的的补充S2A: Guidance on Specific Aspects of Regulatory Genotoxicity Tests forPharmaceuticals受法规管辖的药物基因毒性检验的特定方面的指南S2B: Genotoxicity: A Standard Battery for Genotoxicity Testing forPharmaceuticals基因毒性：药物基因毒性检验的标准S3A: Note for Guidance on Toxicokinetics: The Assessment of SystemicExposure in Toxicity Studies毒物代动力学指南的注释：毒性研究中的全身性暴露量的评估S3B: Pharmacokinetics: Guidance for Repeated Dose Tissue DistributionStudies药物代动力学：重复剂量的组织分布研究指南S4: Single Dose Toxicity Tests单剂量毒性检验S4A: Duration of Chronic Toxicity Testing in Animals (Rodent andNon-Rodent Toxicity Testing)动物体慢性毒性持续时间的检验（啮齿动物和非啮齿动物毒性检验）S5A: Detection of Toxicity to Reproduction for Medicinal Products 药物对生殖发育的毒性的检验S5B(M): Maintenance of the ICH Guideline on Toxicity to Male Fertility: An Addendum to the Guideline on Detection of Toxicity to Reproduction for Medicinal Products对男性生殖能力的毒性的指南的变动：药物对生殖发育的毒性的检验指南增加了一个附录S6: Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals 生物技术生产的药物的临床前安全评价S7A: Safety Pharmacology Studies for Human Pharmaceuticals人用药的安全药理学研究S7B: The Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization(QT Interval Prolongation) By Human Pharmaceuticals药物延迟心室复极化（QT间期）潜在作用的非临床评价S8: Immunotoxicology Studies for Human Pharmaceuticals人用药免疫毒理学研究M3(M): Maintenance of the ICH Guideline on Non-Clinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals药物的对人临床试验的非临床安全研究指南的变动E-Efficacy（有效）E1: The Extent of Population Exposure to Assess Clinical Safety for Drugs Intended for Long-Term Treatment of Non-Life-Threatening Conditions对用于无生命危险情况下长期治疗的药物进行临床安全评估的族群暴露量围E2A: Clinical Safety Data Management: Definitions and Standards forExpedited Reporting临床安全数据管理：速报制度的定义和标准E2B(R): Revision of the E2B(M) ICH Guideline on Clinical Safety DataManagement Data Elements for Transmission of Individual Case Safety Reports个案安全报告送交的临床安全数据管理的数据要素指南（E2B（M））的修订版E2B (M): Maintenance of the Clinical Safety Data Management including: Data Elements for Transmission of Individual Case Safety Reports 临床安全数据管理的变动包括：个案安全报告送交的数据要素E2B(M): Maintenance of the Clinical Safety Data Management includingQuestions and Answers临床安全数据管理的变动，包括问答E2C: Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs临床安全数据管理：已上市药品的周期性安全数据更新报告Addendum to E2C: Periodic Safety Update Reports for Marketed DrugsE2C的附录：已上市药品的周期性安全数据更新报告E2D: Post-Approval Safety Data Management: Definitions and Standards for Expedited Reporting批准后的安全数据管理：速报制度的定义和标准E2E: Pharmacovigilance Planning药物警戒计划E3: Structure and Content of Clinical Study Reports临床研究报告的结构和容E4: Dose-Response Information to Support Drug Registration支持药品注册的剂量－效应资料E5: Ethnic Factors in the Acceptability of Foreign Clinical Data 引入海外临床数据时要考虑的人种因素E6: Good Clinical Practice: Consolidated GuidelineGCP：良好的临床规：统一的指南E7: Studies in Support of Special Populations: Geriatrics对特定族群的支持的研究：老人病学E8: General Considerations for Clinical Trials对临床试验的总的考虑E9: Statistical Principles for Clinical Trials临床试验的统计原则E10: Choice of Control Group and Related Issues in Clinical Trials 临床试验中控制组和有关课题的选择E11: Clinical Investigation of Medicinal Products in the PediatricPopulation小儿科药物的临床调查E12A: Principles for Clinical Evaluation of New Antihypertensive Drugs新抗高血压药物的临床评价原则E14: The Clinical Evaluation of QT/QTc Interval Prolongation andProarrhythmic Potential for Non-Antiarrhythmic Drugs非抗心率失常药物的QT/QTc 间期和致心率失常潜在作用的临床评价Multidisciplinary Guidelines 多学科兼容的指南M1: Medical Terminology医学术语M2: Electronic Standards for Transmission of Regulatory Information (ESTRI)药政信息传递之电子标准M3: Timing of Pre-clinical Studies in Relation to Clinical Trials (SeeSafety Topics)有关临床试验的临床前研究的时间安排M4: The Common Technical Document (See CTD section for complete Status of the guidelines)通用技术文件（见有关CTD章节）M5: Data Elements and Standards for Drug Dictionaries药物词典的数据要素和标准临床试验常用的英文缩略语TTP： time-to-progression 疾病进展时间SAE： severity Adverse Event 严重不良事件AE： Adverse Event 不良事件SOP： Standard Operating Procedure 标准操作规程CRF： Case Report form 病例报告表DLT：剂量限制毒性MTD：最大耐受剂量KPS： Karnofsky Performance Status行为状态评分CR： complete response完全缓解PR： partial response部分缓解SD：病情稳定PD： progressive disease病情进展CTC：常用药物毒性标准IEC： independent ethics committee 独立伦理委员会IRB ： institutional review board 伦理委员会CRA：临床研究助理CRO： Contract Research Organization 合同研究组织DFS： Disease Free Survival 无病生存期OS：（Overall Survival）总生存时间IC： Informed consent 知情同意ADR： Adverse Drug Reaction 不良反应GAP：Good Agricultural Practice 中药材种植管理规GCP：Good Clinical Practice 药物临床试验质量管理规GLP：Good Laboratory Practice 药品实验室管理规GMP：Good Manufacturing Practice 药品生产质量管理规GSP：Good Supply Practice 药品经营质量管理规GUP：Good Use Practice 药品使用质量管理规PI ：Principal investigator 主要研究者CI： Co-inveatigator 合作研究者SI ：Sub-investigator 助理研究者COI ：Coordinating investigtor 协调研究者DGMP：医疗器械生产质量管理规ICF： Informed consent form 知情同意书RCT ： randomized controlled trial, 随机对照试验NRCCT： non-randomized concurrent controlled trial, 非随机同期对照试验EBM： evidence-based medicine 循证医学RCD： randomized cross-over disgn 随机交叉对照试验HCT： historial control trial, 历史对照研究RECIST： Response Evaluation Criteria In Solid Tumors. 实体瘤疗效反应的评价标准QC： Quality Control质量控制UADR： Unexpected Adverse Drug Reaction，非预期药物不良反应。
临床试验数据管理工作技术指南51577
附件临床试验数据管理工作技术指南一、概述临床试验数据质量是评价临床试验结果的基础。
为了确保临床试验结果的准确可靠、科学可信，国际社会和世界各国都纷纷出台了一系列的法规、规定和指导原则，用以规范临床试验数据管理的整个流程。
同时，现代新药临床试验的发展和科学技术的不断进步，特别是计算机、网络的发展又为临床试验及其数据管理的规范化提供了新的技术支持，也推动了各国政府和国际社会积极探索临床试验及数据管理新的规范化模式。
（一）国内临床试验数据管理现状我国的《药物临床试验质量管理规范》（Good Clinical Practice，GCP）对临床试验数据管理提出了一些原则要求，但关于具体的数据管理操作的法规和技术规定目前还处于空白。
由于缺乏配套的技术指导原则，我国在药物临床试验数据管理方面的规范化程度不高，临床试验数据管理质量良莠不齐，进而影响到新药有效性和安全性的客观科学评价。
此外，国内临床试验中电子化数据管理系统的开发和应用尚处于起步阶段，临床试验的数据管理模式大多基于纸质病例报告表（Case Report Form，CRF）的数据采集阶段，电子化数据采集与数据管理系统应用有待推广和普及。
同时，由于缺乏国家数据标准，同类研究的数据库之间难以做到信息共享。
（二）国际临床试验数据管理简介国际上，人用药品注册技术要求国际协调会议的药物临床研究质量管理规范（以下简称ICH E6 GCP）对临床试验数据管理有着原则性要求。
对开展临床试验的研究者、研制厂商的职责以及有关试验过程的记录、源数据、数据核查等都直接或间接地提出了原则性的规定，以保证临床试验中获得的各类数据信息真实、准确、完整和可靠。
各国也颁布了相应的法规和指导原则，为临床试验数据管理的标准化和规范化提供具体的依据和指导。
如：美国21号联邦法规第11部分（21 CFR Part 11）对临床试验数据的电子记录和电子签名的规定（1997年），使得电子记录、电子签名与传统的手写记录与手写签名具有同等的法律效力，从而使得美国食品药品管理局（FDA）能够接受电子化临床研究材料。
(2021年整理)临床英语术语缩写表
（完整）临床英语术语缩写表编辑整理：尊敬的读者朋友们：这里是精品文档编辑中心，本文档内容是由我和我的同事精心编辑整理后发布的，发布之前我们对文中内容进行仔细校对，但是难免会有疏漏的地方，但是任然希望（（完整）临床英语术语缩写表）的内容能够给您的工作和学习带来便利。
同时也真诚的希望收到您的建议和反馈，这将是我们进步的源泉，前进的动力。
本文可编辑可修改，如果觉得对您有帮助请收藏以便随时查阅，最后祝您生活愉快业绩进步，以下为（完整）临床英语术语缩写表的全部内容。
临床研究常用术语缩写表SOP 类型缩写表OP 操作规程Operating Procedures WI 工作指南Work InstructionsTP 模板TemplateFM 批准的标准表格Approved Standard FormsOD 其他文件Other Documents业务部门缩写表/ Functional Area Abbreviation Table: BS 生物统计BiostatisticsBD 业务拓展Business DevelopmentCM 临床监查/运营Clinical Monitoring/OperationDM 数据管理Data ManagementIT 信息技术Information TechnologyMS 医学科学服务Medical Science ServicePM 项目管理Project ManagementQA 质量保证Quality AssuranceRM 记录管理Records ManagementRA 注册事务Regulatory AffairsSM SOP 管理SOP ManagementST 研究中心管理服务Site Management ServiceTR 培训Training试验主文档：（TMF）Trial Master FilePMF 项目管理文件夹Project Management FileCCF 申办方临床研究文件夹Central Clinical File CIF 申办方-研究者文件夹Central Investigator File ISF 研究者文件夹Investigator Site FileBSF 生物统计学文件夹Biostatistics Study File DMSF 数据管理研究文件夹Data Management Study File。
药物临床试验中生物样本管理常见问题及措施建议
药物临床试验中生物样本管理常见问题及措施建议Δ谢江川＊，谢林利，马攀，潘辛梅，曹丽亚，张馨，陈勇川 #（陆军军医大学第一附属医院药学部，重庆 400038）中图分类号 R 951 文献标志码 A 文章编号 1001-0408（2024）05-0524-05DOI 10.6039/j.issn.1001-0408.2024.05.03摘要 目的 为完善药物临床试验生物样本管理相关标准操作规程（SOP ）及生物样本的管理提供参考。
方法 以《药物临床试验质量管理规范》《药物临床试验数据现场核查要点》《人类遗传资源管理条例实施细则》《药物临床试验机构资格认定检查细则》为参照，根据笔者临床试验项目的管理经验，通过统计质控表、申办方上报的方案偏离（PD ），对2016年7月－2023年5月笔者负责管理的药物临床试验项目在生物样本管理方面出现的不规范操作进行分析，并提出生物样本规范化管理的建议。
结果与结论 纳入了60项药物临床试验项目，共发现生物样本管理相关不规范项101条。
生物样本采集、保存、处理为生物样本管理不规范操作发生率最高的环节，不规范项条数分别占总条数的37.62%、25.74%、21.78%。
规范生物样本的管理需多方努力，比如机构办及伦理委员会在项目立项时对试验方案、知情同意书、遗传办申请书中涉及生物样本采集及处理的一致性等进行仔细审核，项目启动时机构办质控员应关注授权的人员是否出席并参加培训，项目开展阶段主要研究者、研究护士、采集人员、处理人员、运送人员、中心实验室相关人员、机构办质控员是否各司其职。
在此基础上，生物样本管理各参与方应做好有效沟通，发现问题及时上报，并针对关键环节进行专项学习。
关键词 药物临床试验；生物样本；生物样本管理Common problems and suggestions of biological sample management in drug clinical trials XIE Jiangchuan ，XIE Linli ，MA Pan ，PAN Xinmei ，CAO Liya ，ZHANG Xin ，CHEN Yongchuan （Dept. of Pharmacy ， the First Affiliated Hospital of Army Medical University ，Chongqing 400038，China ）ABSTRACTOBJECTIVE To provide a reference for improving the relevant standard operating procedures （SOP ） and biologicalsample management in drug clinical trials. METHODS According to Good Clinical Practice ， Data On-site Verification Points of Drugs Clinical Trials ， Human Genetic Resources Management Regulations Implementation Rules ， Qualification Examination Rules of Drug Clinical Trials Institution ， based on the experience of managing clinical trials programs ， the irregularities in biological samples management were analyzed by using statistical quality control tables and protocol deviation （PD ） reported by sponsors ， in the context of the quality control of drug clinical trials projects managed by the author from July 2016 to May 2023. The precautions in various aspects of sample management were put forward. RESULTS & CONCLUSIONS A total of 101 biospecimen-related irregularities were found in the 60 drug clinical trials projects. Biological sample collection ， preservation ， and handling were the aspects with the highest incidence of irregular operations in biological sample management ， accounting for 37.62%， 25.74%， and 21.78%， respectively. Regulating the management of biospecimens requires multiple efforts. The institutional office and the ethics committee carefully reviewed the consistency of the protocols ， informed consent ， and genetic office application involving biospecimen collection and handling when the project was initiated. Institutional office quality controllers should pay attention to the attendance and training of authorized personnel at project initiation. The principal investigator ， research nurse ， collector ， handler ， transporter ， relevant personnel of the central laboratory ， and institutional office quality controller have their roles during the project implementation phase. On this basis ， all parties involved in the management of biological samples should do a good job of effective communication ， find problems and report them in time ， and conduct special studies on key aspects.KEYWORDSdrug clinical trials ； biological sample ； biological sample management生物样本（如血浆、血清、尿液、粪便、组织和细胞等）的管理是药物临床试验中非常重要的环节，涵盖生物样本采集、保存、运输、检测以及检测后的处理等，其不仅影响试验的最终结果，而且生物样本及其信息的安全还关系着种族基因信息保密、公众健康、国家安全和社会公共利益[1]。
药物临床试验中的数据管理与质量控制
目前临床试验受试者很多是门诊患者，鉴于我国很多医院门诊病历多由患者自带， 电子病历又未普及的情况，为完整保存临床试验的原始资料，可以设计“研究病历”。
研究病历作为临床试验受试者的源文件（ｓｏｕｒｃｅ ｄｏｃｕｍｅｎｔ）应保存于各临床试验机构。 设计时，应避免研究病历与病例报告表（ｃａｓｅ
ｒｅｐｏｒｔ
药物临床试验中的数据管理与质量控制
张锡玮张君 （辽宁中医药大学附属医院 沈阳 １１００３２）
［摘要］新药临床试验中数据管理与质量控制贯穿于整个临床研究过程。本文从临床试验 准备、临床试验观察期间、临床观察结束三个阶段阐述了数据管理的基本内容、步骤， 以及相关研究人员进行质量控制的职责。 ［关键词］临床试验；数据管理；质量控制
３．２数据库建立与数据录入
数据管理员在进行数据录入前，要了解病例报告表中各项目的内容及编码情况，将 编码工作过程记录于编码本保存。数据库命名应规范、易读、易查找，用适当的程序保
证数据库的保密性，应具有计算机数据库的维护和支持程序口１，保证其正确、完全和保 密。数据库建立后应试运行，以保证其可靠性。数据管理员应根据拟定的统计分析计划
间的逻辑关系，防止研究者的疏忽造成数据偏失，确保数据质量的真实、科学。经核查
准确无误后，监查员需逐份病例填写“监查员审核页”，并完成“数据一致性检查报告”。
３．临床观察结束阶段此阶段数据管理员和统计分析人员负主要责任ｏ
３．１数据移交
经过监查员检查后的病例报告表，由监查员核查签字后，及时送交临床试验数据管 理员。对于完成的病例报告表在研究者、监查员、数据管理员之间的传送应有专门的记 录，收到时应有相应的签名，记录需妥善保存。
３。
由主要研究者、申办者、监查员、数据管理员和生物统计专业人员在揭盲前，对数 据库内容进行盲态核查，其内容包括试验完成情况（含脱落受试者清单）、入选／排除标 准检查、完整性检查、逻辑一致性检查、离群数据检查、时间窗检查、合并用药检查、 不良事件等数据检查。盲态审核后对数据库进行锁定。锁定后的数据文件原则上不可再 做改动。如数据库锁定之后发现问题，经确认后可在统计分析中进行修正，并作记录和 说明。至此，锁定后的数据用于统计分析，并最终得出统计报告。 我院药物临床试验机构成立了“专家指导委员会”和“临床试验质量监察委员会”．
临床试验数据管理工作技术指南
【下载本文档，可以自由复制内容或自由编辑修改内容，更多精彩文章，期待你的好评和关注，我将一如既往为您服务】附件临床试验数据管理工作技术指南一、概述临床试验数据质量是评价临床试验结果的基础。
为了确保临床试验结果的准确可靠、科学可信，国际社会和世界各国都纷纷出台了一系列的法规、规定和指导原则，用以规范临床试验数据管理的整个流程。
同时，现代新药临床试验的发展和科学技术的不断进步，特别是计算机、网络的发展又为临床试验及其数据管理的规范化提供了新的技术支持，也推动了各国政府和国际社会积极探索临床试验及数据管理新的规范化模式。
（一）国内临床试验数据管理现状我国的《药物临床试验质量管理规范》（Good Clinical Practice，GCP）对临床试验数据管理提出了一些原则要求，但关于具体的数据管理操作的法规和技术规定目前还处于空白。
由于缺乏配套的技术指导原则，我国在药物临床试验数据管理方面的规范化程度不高，临床试验数据管理质量良莠不齐，进而影响到新药有效性和安全性的客观科学评价。
此外，国内临床试验中电子化数据管理系统的开发和应用尚处于起步阶段，临床试验的数据管理模式大多基于纸质病例报告表（Case Report Form，CRF）的数据采集阶段，电子化数据采集与数据管理系统应用有待推广和普及。
同时，由于缺乏国家数据标准，同类研究的数据库之间难以做到信息共享。
（二）国际临床试验数据管理简介国际上，人用药品注册技术要求国际协调会议的药物临床研究质量管理规范（以下简称ICH E6 GCP）对临床试验数据管理有着原则性要求。
对开展临床试验的研究者、研制厂商的职责以及有关试验过程的记录、源数据、数据核查等都直接或间接地提出了原则性的规定，以保证临床试验中获得的各类数据信息真实、准确、完整和可靠。
各国也颁布了相应的法规和指导原则，为临床试验数据管理的标准化和规范化提供具体的依据和指导。
如：美国21号联邦法规第11部分（21 CFR Part 11）对临床试验数据的电子记录和电子签名的规定（1997年），使得电子记录、电子签名与传统的手写记录与手写签名具有同等的法律效力，从而使得美国食品药品管理局（FDA）能够接受电子化临床研究材料。
药物临床试验数据管理与统计分析的计划和报告指导原则
附件药物临床试验数据管理与统计分析的计划和报告指导原则一、前言规范的数据管理计划有助于获得真实、准确、完整和可靠的高质量数据；而详细的统计分析计划则有助于保证统计分析结论正确和令人信服。
为保证临床试验数据的质量和科学评价药物的有效性与安全性，必须事先对数据管理工作和统计学分析原则制定详细的计划书。
在试验完成时，对试验中的数据管理和统计分析工作进行全面完整的总结至关重要，通过数据管理报告真实反映临床试验过程中的数据质量和试验样本特征，通过统计分析报告为临床试验总结报告的内容和研究结论提供主要依据。
因此，在药物上市注册时，监管部门将数据管理计划和报告与统计分析计划和报告视为评价临床试验结果的重要文件和依据。
虽然我国《药物临床试验质量管理规范》（Good Clinical Pr actice，GCP）中对药物临床试验数据管理与统计分析进行了原则要求，且国家食品药品监督管理总局已发布的有关药物临床试验及其统计学的相应技术指南也涉及数据管理和统计分析工作的主要环节，但针对数据管理计划和报告、统计分析计划和报告却没有详细的技术规范和指导性建议。
因此，本技术指导原则对此进行了较为详细的介绍和阐述，并提出具体要求，旨在为临床试验的数据管理和统计分析人员提供技术指导，帮助其更好地完成相关工作以达到监管要求。
二、数据管理的计划和报告（一）一般考虑数据管理计划（Data Management Plan, DMP）是由数据管理人员依据临床试验方案书写的一份动态文件，它详细、全面地规定并记录某一特定临床试验的数据管理任务，包括人员角色、工作内容、操作规范等。
数据管理计划应在试验方案确定之后、第一位受试者筛选之前定稿，经批准后方可执行。
通常数据管理计划需要根据实际操作及时更新与修订。
数据管理工作涉及多个单位或业务部门，包括数据管理、临床研究者、统计分析、医学事务、临床监查、临床稽查等单位或部门。
数据管理的职责可分为负责、参与、审核、批准、告知等，各单位/部门在数据管理各步骤的职责不尽相同。
Clinical Safety Data Management临床安全数据管理(E2A)
European Medicines Agency7 Westferry Circus, Canary Wharf, London, E14 4HB, UKTel. (44-20) 74 18 85 75 Fax (44-20) 75 23 70 40E-mail: mail@emea.eu.int http://www.emea.eu.intJune 1995 CPMP/ICH/377/95ICH Topic E 2 AClinical Safety Data Management: Definitions and Standards for Expedited ReportingStep 5NOTE FOR GUIDANCE ON CLINICAL SAFETY DATA MANAGEMENT:DEFINITIONS AND STANDARDSFOR EXPEDITED REPORTING(CPMP/ICH/377/95)APPROVAL BY CPMP November 1994 DATE FOR COMING INTO OPERATION June 1995CLINICAL SAFETY DATA MANAGEMENT: DEFINITIONS AND STANDARDS FOREXPEDITED REPORTINGICH Harmonised Tripartite Guideline1. INTRODUCTIONIt is important to harmonise the way to gather and, if necessary, to take action on important clinical safety information arising during clinical development. Thus, agreed definitions and terminology, as well as procedures, will ensure uniform Good Clinical Practice standards in this area. The initiatives already undertaken for marketed medicines through the CIOMS-1 and CIOMS-2 Working Groups on expedited (alert) reports and periodic safety update reporting, respectively, are important precedents and models. However, there are special circumstances involving medicinal products under development, especially in the early stages and before any marketing experience is available. Conversely, it must be recognised that a medicinal product will be under various stages of development and/or marketing in different countries, and safety data from marketing experience will ordinarily be of interest to regulators in countries where the medicinal product is still under investigational-only (Phase 1, 2, or 3) status. For this reason, it is both practical and well-advised to regard pre-marketing and post-marketing clinical safety reporting concepts and practices as interdependent, while recognising that responsibility for clinical safety within regulatory bodies and companies may reside with different departments, depending on the status of the product (investigational vs. marketed).There are two issues within the broad subject of clinical safety data management that are appropriate for harmonisation at this time:1. the development of standard definitions and terminology for key aspects of clinicalsafety reporting, and2. the appropriate mechanism for handling expedited (rapid) reporting, in theinvestigational (i.e., pre-approval) phase.The provisions of this guideline should be used in conjunction with other ICH Good Clinical Practice guidelines.TERMINOLOGY ASSOCIATED WITH CLINICAL2. DEFINITIONSANDSAFETY EXPERIENCEA. BasicTermsDefinitions for the terms adverse event (or experience), adverse reaction, and unexpected adverse reaction have previously been agreed to by consensus of the more than 30 Collaborating Centres of the WHO International Drug Monitoring Centre (Uppsala, Sweden). [Edwards, I.R., et al, Harmonisation in Pharmacovigilance. Drug Safety 10(2): 93-102, 1994.] Although those definitions can pertain to situations involving clinical investigations, some minor modifications are necessary, especially to accommodate the pre-approval, development environment.The following definitions, with input from the WHO Collaborative Centre, have been agreed:1. Adverse Event (or Adverse Experience)Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.An adverse event (AE) can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.2. Adverse Drug Reaction (ADR)In the pre-approval clinical experience with a new medicinal product or its new usages, particularly as the therapeutic dose(s) may not be established:all noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions.The phrase "responses to a medicinal products" means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility, i.e., the relationship cannot be ruled out.Regarding marketed medicinal products, a well-accepted definition of an adverse drug reaction in the post-marketing setting is found in WHO Technical Report 498 [1972] and reads as follows:A response to a drug which is noxious and unintended and which occurs at dosesnormally used in man for prophylaxis, diagnosis, or therapy of disease or for modification of physiological function.The old term "side effect" has been used in various ways in the past, usually to describe negative (unfavourable) effects, but also positive (favourable) effects. It is recommended that this term no longer be used and particularly should not be regarded as synonymous with adverse event or adverse reaction.3. Unexpected Adverse Drug ReactionAn adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g., Investigator's Brochure for an unapproved investigational medicinal product). (See section III.C.)B. Serious Adverse Event or Adverse Drug ReactionDuring clinical investigations, adverse events may occur which, if suspected to be medicinal product-related (adverse drug reactions), might be significant enough to lead to important changes in the way the medicinal product is developed (e.g., change in dose, population, needed monitoring, consent forms). This is particularly true for reactions which, in their most severe forms, threaten life or function. Such reactions should be reported promptly to regulators.Therefore, special medical or administrative criteria are needed to define reactions that, either due to their nature ("serious") or due to the significant, unexpected information they provide, justify expedited reporting.To ensure no confusion or misunderstanding of the difference between the terms "serious" and "severe," which are not synonymous, the following note of clarification is provided: The term "severe" is often used to describe the intensity (severity) of a specific event (as in mild, moderate, or severe myocardial infarction); the event itself, however, may be of relatively minor medical significance (such as severe headache). This is not the same as "serious," which is based on patient/event outcome or action criteria usually associated with events that pose a threat to a patient's life or functioning. Seriousness (not severity) serves as a guide for defining regulatory reporting obligations.After reviewing the various regulatory and other definitions in use or under discussion elsewhere, the following definition is believed to encompass the spirit and meaning of them all:A serious adverse event (experience) or reaction is any untoward medicaloccurrence that at any dose:indeath,• resultslife-threatening,• isNOTE:T he term "life-threatening" in the definition of "serious" refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe.• requires inpatient hospitalisation or prolongation of existing hospitalisation,• results in persistent or significant disability/incapacity, or• is a congenital anomaly/birth defect.Medical and scientific judgement should be exercised in deciding whether expedited reporting is appropriate in other situations, such as important medical events that may not be immediately life-threatening or result in death or hospitalisation but may jeopardise the patient or may require intervention to prevent one of the other outcomes listed in the definition above. These should also usually be considered serious.Examples of such events are intensive treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalisation; or development of drug dependency or drug abuse.C. Expectedness of an Adverse Drug ReactionThe purpose of expedited reporting is to make regulators, investigators, and other appropriate people aware of new, important information on serious reactions. Therefore, such reporting will generally involve events previously unobserved or undocumented, and a guideline is needed on how to define an event as "unexpected" or "expected" (expected/unexpected from the perspective of previously observed, not on the basis of what might be anticipated from the pharmacological properties of a medicinal product).As stated in the definition (II.A.3.), an "unexpected" adverse reaction is one, the nature or severity of which is not consistent with information in the relevant source document(s). Until source documents are amended, expedited reporting is required for additional occurrences of the reaction.The following documents or circumstances will be used to determine whether an adverse event/reaction is expected:1. For a medicinal product not yet approved for marketing in a country, a company'sInvestigator's Brochure will serve as the source document in that country. (See section III.F. and ICH Guideline for the Investigator's Brochure.)2. Reports which add significant information on specificity or severity of a known,already documented serious ADR constitute unexpected events. For example, an event more specific or more severe than described in the Investigator's Brochure would be considered "unexpected". Specific examples would be (a) acute renal failure as a labeled ADR with a subsequent new report of interstitial nephritis and (b) hepatitis with a first report of fulminant hepatitis.3. STANDARDS FOR EXPEDITED REPORTINGA. What Should be Reported?1. Single Cases of Serious, Unexpected ADRsAll adverse drug reactions (ADRs) that are both serious and unexpected are subject to expedited reporting. This applies to reports from spontaneous sources and from any type of clinical or epidemiological investigation, independent of design or purpose. It also applies to cases not reported directly to a sponsor or manufacturer (for example, those found in regulatory authority-generated ADR registries or in publications). The source of a report (investigation, spontaneous, other) should always be specified.Expedited reporting of reactions which are serious but expected will ordinarily be inappropriate. Expedited reporting is also inappropriate for serious events from clinical investigations that are considered not related to study product, whether the event is expected or not. Similarly, non-serious adverse reactions, whether expected or not, will ordinarily not be subject to expedited reporting.Information obtained by a sponsor or manufacturer on serious, unexpected reports from any source should be submitted on an expedited basis to appropriate regulatory authorities if the minimum criteria for expedited reporting can be met. See section III.B.Causality assessment is required for clinical investigation cases. All cases judged by either the reporting health care professional or the sponsor as having a reasonable suspected causal relationship to the medicinal product qualify as ADRs. For purposes of reporting, adverse event reports associated with marketed drugs (spontaneous reports) usually imply causality. Many terms and scales are in use to describe the degree of causality (attributability) between a medicinal product and an event, such as certainly, definitely, probably, possibly or likely related or not related. Phrases such as "plausible relationship," "suspected causality," or "causal relationship cannot be ruled out" are also invoked to describe cause and effect. However, there is currently no standard international nomenclature. The expression "reasonable causal relationship" is meant to convey in general that there are facts (evidence) or arguments to suggest a causal relationship.Observations2. OtherThere are situations in addition to single case reports of "serious" adverse events or reactions that may necessitate rapid communication to regulatory authorities; appropriate medical and scientific judgement should be applied for each situation. In general, information that mightmaterially influence the benefit-risk assessment of a medicinal product or that would be sufficient to consider changes in medicinal product administration or in the overall conduct of a clinical investigation represents such situations. Examples include:a) For an "expected," serious ADR, an increase in the rate of occurrence which is judgedto be clinically important.b) A significant hazard to the patient population, such as lack of efficacy with a medicinalproduct used in treating life-threatening disease.c) A major safety finding from a newly completed animal study (such ascarcinogenicity).B. Reporting Time Frames1. Fatal or Life-Threatening Unexpected ADRsCertain ADRs may be sufficiently alarming so as to require very rapid notification to regulators in countries where the medicinal product or indication, formulation, or population for the medicinal product are still not approved for marketing, because such reports may lead to consideration of suspension of, or other limitations to, a clinical investigations program. Fatal or life-threatening, unexpected ADRs occurring in clinical investigations qualify for very rapid reporting. Regulatory agencies should be notified (e.g., by telephone, facsimile transmission, or in writing) as soon as possible but no later than 7 calendar days after first knowledge by the sponsor that a case qualifies, followed by as complete a report as possible within 8 additional calendar days. This report must include an assessment of the importance and implication of the findings, including relevant previous experience with the same or similar medicinal products.2. All Other Serious, Unexpected ADRsSerious, unexpected reactions (ADRs) that are not fatal or life-threatening must be filed as soon as possible but no later than 15 calendar days after first knowledge by the sponsor that the case meets the minimum criteria for expedited reporting.3. Minimum criteria for reportingInformation for final description and evaluation of a case report may not be available within the required time frames for reporting outlined above. Nevertheless, for regulatory purposes, initial reports should be submitted within the prescribed time as long as the following minimum criteria are met: an identifiable patient; a suspect medicinal product; an identifiable reporting source; and an event or outcome that can be identified as serious and unexpected, and for which, in clinical investigation cases, there is a reasonable suspected causal relationship. Follow-up information should be actively sought and submitted as it becomes available.ReporttoC. HowThe CIOMS-I form has been a widely accepted standard for expedited adverse event reporting. However, no matter what the form or format used, it is important that certain basic information/data elements, when available, be included with any expedited report, whether in a tabular or narrative presentation. The listing in Attachment 1 addresses those data elements regarded as desirable; if all are not available at the time of expedited reporting, efforts should be made to obtain them. (See section III.B.)All reports must be sent to those regulators or other official parties requiring them (as appropriate for the local situation) in countries where the drug is under development.D. Managing Blinded Therapy CasesWhen the sponsor and investigator are blinded to individual patient treatment (as in a double-blind study), the occurrence of a serious event requires a decision on whether to open (break) the code for the specific patient. If the investigator breaks the blind, then it is assumed the sponsor will also know the assigned treatment for that patient. Although it is advantageous to retain the blind for all patients prior to final study analysis, when a serious adverse reaction is judged reportable on an expedited basis, it is recommended that the blind be broken only for that specific patient by the sponsor even if the investigator has not broken the blind. It is also recommended that, when possible and appropriate, the blind be maintained for those persons, such as biometrics personnel, responsible for analysis and interpretation of results at the study's conclusion.There are several disadvantages to maintaining the blind under the circumstances described which outweigh the advantages. By retaining the blind, placebo and comparator (usually a marketed product) cases are filed unnecessarily. When the blind is eventually opened, which may be many weeks or months after reporting to regulators, it must be ensured that company and regulatory data bases are revised. If the event is serious, new, and possibly related to the medicinal product, then if the Investigator's Brochure is updated, notifying relevant parties of the new information in a blinded fashion is inappropriate and possibly misleading. Moreover, breaking the blind for a single patient usually has little or no significant implications for the conduct of the clinical investigation or on the analysis of the final clinical investigation data. However, when a fatal or other "serious" outcome is the primary efficacy endpoint in a clinical investigation, the integrity of the clinical investigation may be compromised if the blind is broken. Under these and similar circumstances, it may be appropriate to reach agreement with regulatory authorities in advance concerning serious events that would be treated as disease-related and not subject to routine expedited reporting.IssuesE. Miscellaneous1. Reactions Associated with Active Comparator or Placebo TreatmentIt is the sponsor's responsibility to decide whether active comparator drug reactions should be reported to the other manufacturer and/or directly to appropriate regulatory agencies. Sponsors must report such events to either the manufacturer of the active control or to appropriate regulatory agencies. Events associated with placebo will usually not satisfy the criteria for an ADR and, therefore, for expedited reporting.2. Products with More than one Presentation or UseTo avoid ambiguities and uncertainties, an ADR that qualifies for expedited reporting with one presentation of a product (e.g., a dosage form, formulation, delivery system) or product use (e.g., for an indication or population), should be reported or referenced to regulatory filings across other product presentations and uses.It is not uncommon that more than one dosage form, formulation, or delivery system (oral, IM, IV, topical, etc.) of the pharmacologically active compound(s) is under study or marketed; for these different presentations there may be some marked differences in the clinical safety profile. The same may apply for a given product used in different indications or populations (single dose vs. chronic administration, for example). Thus, "expectedness" may be product or product-use specific, and separate Investigator's Brochures may be used accordingly. However, such documents are expected to cover ADR information that applies to all affected product presentations and uses. When relevant, separate discussions of pertinent product-specific or use-specific safety information will also be included.It is recommended that any adverse drug reactions that qualify for expedited reporting observed with one product dosage form or use be cross referenced to regulatory records for all other dosage forms and uses for that product. This may result in a certain amount of overreporting or unnecessary reporting in obvious situations (for example, a report of phlebitis on IV injection sent to authorities in a country where only an oral dosage form is studied or marketed). However, underreporting is completely avoided.Events3. Post-studyAlthough such information is not routinely sought or collected by the sponsor, serious adverse events that occurred after the patient had completed a clinical study (including any protocol-required post-treatment follow-up) will possibly be reported by an investigator to the sponsor. Such cases should be regarded for expedited reporting purposes as though they were study reports. Therefore, a causality assessment and determination of expectedness are needed for a decision on whether or not expedited reporting is required.F. Informing Investigators and Ethics Committees/Institutional Review Boards ofNew Safety InformationInternational standards regarding such communication are discussed within the ICH GCP Guidelines, including the addendum on "Guideline for the Investigator's Brochure." In general, the sponsor of a study should amend the Investigator's Brochure as needed, and in accord with any local regulatory requirements, so as to keep the description of safety information updated.ATTACHMENT 1KEY DATA ELEMENTS FOR INCLUSION IN EXPEDITEDREPORTS OF SERIOUS ADVERSE DRUG REACTIONSThe following list of items has its foundation in several established precedents, including those of CIOMS-I, the WHO International Drug Monitoring Centre, and various regulatory authority forms and guidelines. Some items may not be relevant depending on the circumstances. The minimum information required for expedited reporting purposes is: an identifiable patient, the name of a suspect medicinal product, an identifiable reporting source, and an event or outcome that can be identified as serious and unexpected and for which, in clinical investigation cases, there is a reasonable suspected causal relationship. Attempts should be made to obtain follow-up information on as many other listed items pertinent to the case.Details1. PatientInitialsOther relevant identifier (clinical investigation number, for example)GenderAge and/or date of birthWeightHeight2. Suspected Medicinal Product(s)Brand name as reportedInternational Non-Proprietary Name (INN)Batch numberIndication(s) for which suspect medicinal product was prescribed or testedDosage form and strengthDaily dose and regimen (specify units - e.g., mg, ml, mg/kg)Route of administrationStarting date and time of dayStopping date and time, or duration of treatmentTreatment(s)3. OtherFor concomitant medicinal products (including non-prescription/OTC medicinal products) and non-medicinal product therapies, provide the same information as for the suspected product.4. Details of Suspected Adverse Drug Reaction(s)Full description of reaction(s) including body site and severity, as well as the criterion (or criteria) for regarding the report as serious should be given. In addition to a description of the reported signs and symptoms, whenever possible, attempts should be made to establish a specific diagnosis for the reaction.Start date (and time) of onset of reactionStop date (and time) or duration of reactionDechallenge and rechallenge informationSetting (e.g., hospital, out-patient clinic, home, nursing home)Outcome: information on recovery and any sequelae; what specific tests and/or treatment may have been required and their results; for a fatal outcome, cause of death and a comment on its possible relationship to the suspected reaction should be provided. Any autopsy or other post-mortem findings (including a coroner's report) should also be provided when available. Other information: anything relevant to facilitate assessment of the case, such as medical history including allergy, drug or alcohol abuse; family history; findings from special investigations.5. Details on Reporter of Event (Suspected ADR)NameAddressTelephone numberProfession (speciality)6. Administrative and Sponsor/Company DetailsSource of report: was it spontaneous, from a clinical investigation (provide details), from the literature (provide copy), other?Date event report was first received by sponsor/manufacturerCountry in which event occurredType of report filed to authorities: initial or follow-up (first, second, etc.)Name and address of sponsor/manufacturer/companyName, address, telephone number, and FAX number of contact person in reporting company or institutionIdentifying regulatory code or number for marketing authorisation dossier or clinical investigation process for the suspected product (for example IND or CTX number, NDA number)Sponsor/manufacturer's identification number for the case (this number must be the same for the initial and follow-up reports on the same case).。
药物临床试验常用英文词汇
缩略语英文全称ADE Adverse Drug EventADR Adverse Drug ReactionAE Adverse EventAI Assistant InvestigatorBMI Body Mass IndexCl Co-investigatorCOI Coordinating InvestigatorCRC Clinical Research CoordinatorCRF Case Report FormCRO Contract Research OrganizationCSA Clinical Study ApplicationCTA Clinical Trial ApplicationCTX Clinical Trial ExemptionCTP Clinical Trial ProtocolCTR Clinical Trial ReportDSMB Data Safety and monitoring BoarEDC Electronic Data CaptureEDP Electronic Data ProcessingFDA Food and Drug AdministrationFR Final ReportGCP Good Clinical PracticeGCP Good Laboratory PracticeGMP Good Manufacturing PracticeIB Investigator’s BrochureIC Informed ConsentICF Informed Consent FormICH International Conference on Harmonization IDM Independent Data MonitoringIDMC Independent Data Monitoring Committee IEC Independent Ethics CommitteeIND Investigational New DrugIRB Institutional Review BoardIVD In Vitro DiagnosticIVRS Interactive Voice Response SystemMA Marketing Approval/AuthorizationMCA Medicines Control AgencyMHW Ministry of Health and Welfare日NDA New Drug ApplicationNEC New Drug EntityNIH National Institutes of HealthNCE New chemical entityNDA New drug applicationNMRNon-clinical StudyNon-inferiorityNon-parametric statisticsObedienceODROpen-labelOptional titrationOriginal medical recordOutcomeOutcome AssessmentOutcome assessmentOutcome measurementOutlierParallel group designParameter estimationParametric statisticsPatient filePatient historyPP Per protocolPlaceboPlacebo controlPolytomiesPowerPrecisionPreclinical studyPrimary endpointPrimary variablePI Principle investigatorPL Product licenseProtocolProtocol AmendmentsQA Quality assuranceQAU Quality assurance unitQC Quality controlPI Principal InvestigatorPL Product LicensePM APre-market Approval (Application)PSI Statisticians in the Pharmaceutical Industry QA Quality AssuranceQC Quality ControlRA Regulatory AuthoritiesSA Site AssessmentSAE Serious Adverse EventSAP Statistical Analysis PlanSAR Serious Adverse ReactionSD Source Data/DocumentSD Subject DiarySFDA State Food and Drug AdministrationSDV Source Data VerificationSEL Subject Enrollment LogSI Sub-investigatorSI Sponsor-InvestigatorSIC Subject Identification CodeSOP Standard Operating ProcedureSPL Study Personnel ListSSL Subject Screening LogT&R Test and Reference ProductUAE Unexpected Adverse EventWHO World Health OrganizationWHO International Conference of Drug Regulatory Authorities WHO-ICDRAAccuracyAC Active control,ADR Adverse drug reactionAE Adverse eventAdverse medical eventsAdverse reactionAlbALD Approximate Lethal DoseALPAlpha spending functionALTAnalysis setsApprovalAssistant investigatorASTATRAUCssAuditAudit or inspectionAudit reportAuditorBiasBioequivalenceBlank controlBlind codesBlind reviewBlinding methodBlinding/maskingBlockBlock sizeCarryover effectCase historyCRF Case report form/ case record formCategorical variableCavCDCLClinical equivalenceClinical studyClinical study reportClinical trialCTA Clinical trial applicationCTX Clinical trial exemptionCTP Clinical trial protocolClinical trial/ study reportCmaxCo-investigatorComparisonComplianceComposite variableCATD Computer-assisted trial designConfidence intervalConfidence levelConsistency testCRO Contract research organization Contract/ agreementControl groupCoordinating committeeCreaCrossover designCross-over StudyCssCureData managementDatabaseDescriptive statistical analysisDFDichotomiesDiviationDocumentationDose-reaction relationDouble dummyDouble dummy techniqueDrop outDSCEffectivenessEDC Electronic data captureEDP Electronic data processingEmergency envelopeEnd pointEndpoint criteria/ measurementEquivalenceEssential DocumentationEthics committeeExcellentExclusion criteriaFactorial designFailureFinal pointFixed-dose procedureForced titrationFull analysis setGC-FTIRGC-MSGeneric drugGlobal assessment variableGLUGCP Good clinical practice,GMP Good manufacture practiceGLP Good non-clinical laboratory practice Group sequential designHEV Health economic evaluationHypothesis testImprovementInclusion CriteriaQuery list /query formRandomizationRange checkRating scaleReference ProductRA Regulatory authoritiesReplicationRSDRun inSafety evaluationSafety setSample sizeScale of ordered categorical ratingsSecondary variableSequenceSAE Serious adverse eventSAR Serious adverse reactionSeriousnessSeveritySignificant levelSimple RandomizationSingle blindingSite auditSOPSD Source dataSDV Source data verificationSD Source documentSpecificitySponsorSponsor-investigatorStandard curveSOP Standard operating procedureStatisticStatistical analysis planStatistical modelStatistical tablesStratifiedStudy auditStudy SiteSubgroupSub-investigatorSubjectSubject diarySubject EnrollmentSubject enrollment logSubject identification code SICSubject Identification Code ListSubject RecruitmentSubject screening logSuperioritySurvival analysisSXRDSystem AuditTl/2Target variableT-BILT-CHOTest ProductTGTLC、 HPLCTmaxTPTransformationTreatment groupTrial errorTrial Initial MeetingTrial Master FileTrial objectiveTrial siteTriple blindingTB total bilirubinDB direct bilirubinTP total proteinALB albuminGLOB globulinUREA ureaCREA creatinineUA uric acidGLU glucoseALT alanine amiotransferaseAST aspartate aminotransferaseGGT y-glutamyl transpeptadaseCK creatine kinaseCK-MB creatine kinase-MBLDH lactate dehydrogenasea-HBD a-hydroxybutyric dehydrogenaseaAMY serum amylaseTG triglycerideCHOL cholesterolHDL-c high-density lipoprotein cholesterolLDL-c low-density lipoprotein cholesterol VLDL very low-density lipoproteinCa serum calciumMg serum magnesiumIP inorganic phosphateALP alkaline phosphataseTBA total biliary acidASO antistreptolysina-AG a—acid glycoproteinaCRP C-reactive protein CRF rheumatoid factorMTP mili-total proteinIgG immunoglobin GIgA immunoglobin AIgM immunoglobin MC3complement C3C4complement C4WBC white blood cell countGR%granulocyteLY%lymphocyteMID%EOS%eosimophilAL%allergy lymphocyteST%RBC red blood cellHGB hemoglobinHCT hematocritMCV mean corpusular volumeMCH mean corpusular hemoglobinMCHC mean corpusular hemoglobin concerntration RDW red blood cell volume distribution widthPLT/BPC platelet count/blood platelet countMPV mean platelet volumePCT plateletocritPDW platelet distribution widthPH acidityNIT nitriteGLU glucoseSG specific gravityPRO proteinBLD bloodBIL bilirubinURO urobilinogenWBC white blood celladdishaddish count/HP high power objective /LP low power objective OB occult blood test CSF cerebrospinal Pandy pandy中文全称药物不良事件药物不良反应不良事件助理研究者体质指数合作研究者协调研究者临床研究协调者病历报告表合同研究组织临床研究屮请临床试验申请临床试验免责临床试验方案临床试验报告d数据安全及监控委员会电子数据采集系统电子数据处理系统美国食品与药品管理局总结报告药物临床试验质量管理规范药物非临床试验质量管理规范药品生产质量管理规范研究者手册知情同意知情同意书国际协调会议独立数据监察独立数据监察委员会独立伦理委员会新药临床研究机构审查委员会体外诊断互动语音应答系统上市许可证英国药品监督局本卫生福利部新药申请新化学实体国家卫生研究所（美国）新化学实体新药申请核磁共振谱非临床研宄非劣效性非参数统计方法依从性旋光光谱非盲随意滴定原始医疗记录结果结果评价结果指标评价结果指标离群值平行组设计参数估计参数统计方法病人档案病历符合方案集安慰剂安慰剂对照多分类检验效能精密度临床前研究主要终点主要变量主要研究者产品许可证试验方案修正案质量保证质量保证部门质量控制主要研究者产品许可证上市前许可（申请）制药业统计学家协会质量保证质量控制监督管理部门现场评估严重不良事件统计分析计划严重不良反应原始数据/文件受试者日记国家食品药品监督管理局原始数据核准受试者入选表助理研究者申办研究者受试者识别代码标准操作规程研究人员名单受试者筛选表受试和参比试剂预料外不良事件世界卫生组织WHO国际药品管理当局会议准确度阳性对照,活性对照药物不良反应不良事件不良医学事件药物不良反应白蛋白近似致死剂量碱性磷酸酶消耗函数丙氨酸氨基转换酶统计分析的数据集批准助理研究者天门冬酸氨基转换酶衰减全反射法稳态血药浓度-时间曲线下面积稽查稽查/视察稽查报告稽查员偏性，偏倚生物等效应空白对照编制盲底盲态审核，盲态检查盲法盲法/设盲层每段的长度延滞效应病历病例报告表病例记录表分类变量平均浓度圆二色谱清除率临床等效应临床研究临床试验的总结报告临床试验临床试验申请临床试验免责临床试验方案临床试验报告峰浓度合作研究者对照依从性复合变量计算机辅助试验设计可信区间置信水平一致性检验合同研究组织协议/合同对照组协调委员会肌酐交叉设计交叉研究稳浓度痊愈数据管理建立数据库描述性统计分析波动系统二分类偏差记录/文件剂量-反应关系双模拟双盲双模拟技术脱落差示扫描热量计疗效电子数据采集系统电子数据处理系统应急信件终点终点指标等效性必需文件伦理委员会显效排标准析因设计无效失败终点固定剂量法强制滴定全分析集气相色谱-傅利叶红外联用气相色谱-质谱联用通用名药全局评价变量血糖药物临床试验质量管理规范药品生产质量管理规范药物非临床研究质量管理规范成组序贯设计健康经济学评价假设检验好转入选表准应用疑问表随机范围检查量表参比制剂监督管理部门可重复日内和日间相对标准差准备期安全性评价安全性评价的数据集样本量样本大小有序分类指标次要变量试验次序严重不良事件严重不良反应严重性严重程度检验水准简单随机单盲试验机构稽查试验室的标准操作规程原始数据原始数据核准原始文件特异性申办者申办研究者标准曲线标准操作规程统计量统计分析计划统计模型统计分析表分 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