ICH Topic E 6 (R1) Guideline for Good Clinical Practice

European Medicines Agency July 2002 CPMP/ICH/135/95 ICH Topic E 6 (R1) Guideline for Good Clinical Practice Step 5 NOTE FOR GUIDANCE ON GOOD CLINICAL PRACTICE (CPMP/ICH/135/95) TRANSMISSION TO CPMP FINAL APPROVAL BY CPMP DATE FOR COMING INTO OPERATION POST STEP ERRATA (linguistic minor corrections) July 1996 July 1996 January 1997 July 2002 7 Westferry Circus, Canary Wharf, London, E14 4HB, UK Tel. (44-20) 74 18 85 75 Fax (44-20) 75 23 70 40 E-mail: mail@emea.eu.int http://www.emea.eu.int ©EMEA 2006 Reproduction and/or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged TABLE OF CONTENT INTRODUCTION.........................................................................................................................5 1. GLOSSARY............................................................................................................................5 1.1 ADVERSE DRUG REACTION (ADR) ...................................................................................5 1.2 ADVERSE EVENT (AE).......................................................................................................5 1.3 AMENDMENT (TO THE PROTOCOL).....................................................................................5 1.4 APPLICABLE REGULATORY REQUIREMENT(S)...................................................................5 1.5 APPROVAL (IN RELATION TO INSTITUTIONAL REVIEW BOARDS) .......................................5 1.6 AUDIT................................................................................................................................5 1.7 AUDIT CERTIFICATE ..........................................................................................................6 1.8 AUDIT REPORT ..................................................................................................................6 1.9 AUDIT TRAIL.....................................................................................................................6 1.10 BLINDING/MASKING..........................................................................................................6 1.11 CASE REPORT FORM (CRF)...............................................................................................6 1.12 CLINICAL TRIAL/STUDY ....................................................................................................6 1.13 CLINICAL TRIAL/STUDY REPORT.......................................................................................6 1.14 COMPARATOR (PRODUCT).................................................................................................6 1.15 COMPLIANCE (IN RELATION TO TRIALS).............................................................................6 1.16 CONFIDENTIALITY .............................................................................................................6 1.17 CONTRACT.........................................................................................................................6 1.18 COORDINATING COMMITTEE .............................................................................................6 1.19 COORDINATING INVESTIGATOR.........................................................................................7 1.20 CONTRACT RESEARCH ORGANIZATION (CRO)..................................................................7 1.21 DIRECT ACCESS.................................................................................................................7 1.22 DOCUMENTATION..............................................................................................................7 1.23 ESSENTIAL DOCUMENTS....................................................................................................7 1.24 GOOD CLINICAL PRACTICE (GCP).....................................................................................7 1.25 INDEPENDENT DATA-MONITORING COMMITTEE (IDMC) (DATA AND SAFETY MONITORING BOARD,MONITORING COMMITTEE,DATA MONITORING COMMITTEE)..................7 1.26 IMPARTIAL WITNESS .........................................................................................................7 1.27 INDEPENDENT ETHICS COMMITTEE (IEC)..........................................................................7 1.28 INFORMED CONSENT .........................................................................................................8 1.29 INSPECTION .......................................................................................................................8 1.30 INSTITUTION (MEDICAL)....................................................................................................8 1.31 INSTITUTIONAL REVIEW BOARD (IRB)..............................................................................8 1.32 INTERIM CLINICAL TRIAL/STUDY REPORT ........................................................................8 1.33 INVESTIGATIONAL PRODUCT .............................................................................................8 1.34 INVESTIGATOR...................................................................................................................8 1.35 INVESTIGATOR / INSTITUTION............................................................................................8 1.36 INVESTIGATOR`S BROCHURE..............................................................................................8 1.37 LEGALLY ACCEPTABLE REPRESENTATIVE.........................................................................8 1.38 MONITORING.....................................................................................................................9 1.39 MONITORING REPORT........................................................................................................9 1.40 MULTICENTRE TRIAL.........................................................................................................9 1.41 NONCLINICAL STUDY ........................................................................................................9 1.42 OPINION (IN RELATION TO INDEPENDENT ETHICS COMMITTEE).........................................9 1.43 ORIGINAL MEDICAL RECORD ............................................................................................9 1.44 PROTOCOL.........................................................................................................................9 1.45 PROTOCOL AMENDMENT...................................................................................................9 © EMEA 2006 2 1.46 QUALITY ASSURANCE (QA)..............................................................................................9 1.47 QUALITY CONTROL (QC)..................................................................................................9 1.48 RANDOMIZATION ..............................................................................................................9 1.49 REGULATORY AUTHORITIES..............................................................................................9 1.50 SERIOUS ADVERSE EVENT (SAE) OR SERIOUS ADVERSE DRUG REACTION (SERIOUS ADR) 9 1.51 SOURCE DATA.................................................................................................................10 1.52 SOURCE DOCUMENTS......................................................................................................10 1.53 SPONSOR .........................................................................................................................10 1.54 SPONSOR-INVESTIGATOR ................................................................................................10 1.55 STANDARD OPERATING PROCEDURES (SOPS).................................................................10 1.56 SUBINVESTIGATOR..........................................................................................................10 1.57 SUBJECT/TRIAL SUBJECT.................................................................................................10 1.58 SUBJECT IDENTIFICATION CODE......................................................................................10 1.59 TRIAL SITE ......................................................................................................................10 1.60 UNEXPECTED ADVERSE DRUG REACTION.......................................................................10 1.61 VULNERABLE SUBJECTS..................................................................................................11 1.62 WELL-BEING (OF THE TRIAL SUBJECTS)...........................................................................11 2. THE PRINCIPLES OF ICH GCP.....................................................................................11 3. INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE (IRB/IEC).....................................................................................................................................12 3.1 RESPONSIBILITIES............................................................................................................12 3.2 COMPOSITION,FUNCTIONS AND OPERATIONS.................................................................13 3.3 PROCEDURES...................................................................................................................13 3.4 RECORDS.........................................................................................................................14 4. INVESTIGATOR................................................................................................................14 4.1 INVESTIGATOR`S QUALIFICATIONS AND AGREEMENTS....................................................14 4.2 ADEQUATE RESOURCES ..................................................................................................15 4.3 MEDICAL CARE OF TRIAL SUBJECTS ...............................................................................15 4.4 COMMUNICATION WITH IRB/IEC....................................................................................15 4.5 COMPLIANCE WITH PROTOCOL........................................................................................16 4.6 INVESTIGATIONAL PRODUCT(S).......................................................................................16 4.7 RANDOMIZATION PROCEDURES AND UNBLINDING..........................................................17 4.8 INFORMED CONSENT OF TRIAL SUBJECTS .......................................................................17 4.9 RECORDS AND REPORTS..................................................................................................20 4.10 PROGRESS REPORTS ........................................................................................................20 4.11 SAFETY REPORTING ........................................................................................................20 4.12 PREMATURE TERMINATION OR SUSPENSION OF A TRIAL.................................................21 4.13 FINAL REPORT(S) BY INVESTIGATOR...............................................................................21 5. SPONSOR ............................................................................................................................21 5.1 QUALITY ASSURANCE AND QUALITY CONTROL..............................................................21 5.2 CONTRACT RESEARCH ORGANIZATION (CRO)...............................................................22 5.3 MEDICAL EXPERTISE.......................................................................................................22 5.4 TRIAL DESIGN.................................................................................................................22 5.5 TRIAL MANAGEMENT, DATA HANDLING, AND RECORD KEEPING...................................22 5.6 INVESTIGATOR SELECTION..............................................................................................24 5.7 ALLOCATION OF RESPONSIBILITIES.................................................................................24 5.8 COMPENSATION TO SUBJECTS AND INVESTIGATORS .......................................................24 5.9 FINANCING......................................................................................................................24 5.10 NOTIFICATION/SUBMISSION TO REGULATORY AUTHORITY(IES).....................................24 © EMEA 2006 3 5.11 CONFIRMATION OF REVIEW BY IRB/IEC.........................................................................25 5.12 INFORMATION ON INVESTIGATIONAL PRODUCT(S)..........................................................25 5.13 MANUFACTURING,PACKAGING,LABELLING, AND CODING INVESTIGATIONAL PRODUCT(S)................................................................................................................................25 5.14 SUPPLYING AND HANDLING INVESTIGATIONAL PRODUCT(S) ..........................................26 5.15 RECORD ACCESS .............................................................................................................26 5.16 SAFETY INFORMATION.....................................................................................................27 5.17 ADVERSE DRUG REACTION REPORTING ..........................................................................27 5.18 MONITORING...................................................................................................................27 5.19 AUDIT..............................................................................................................................29 5.20 NONCOMPLIANCE ............................................................................................................30 5.21 PREMATURE TERMINATION OR SUSPENSION OF A TRIAL.................................................30 5.22 CLINICAL TRIAL/STUDY REPORTS...................................................................................30 5.23 MULTICENTRE TRIALS.....................................................................................................30 6. CLINICAL TRIAL PROTOCOL AND PROTOCOL AMENDMENT(S) ...................31 6.1 GENERAL INFORMATION..................................................................................................31 6.2 BACKGROUND INFORMATION..........................................................................................31 6.3 TRIAL OBJECTIVES AND PURPOSE....................................................................................31 6.4 TRIAL DESIGN .................................................................................................................32 6.5 SELECTION AND WITHDRAWAL OF SUBJECTS..................................................................32 6.6 TREATMENT OF SUBJECTS ...............................................................................................32 6.7 ASSESSMENT OF EFFICACY..............................................................................................33 6.8 ASSESSMENT OF SAFETY .................................................................................................33 6.9 STATISTICS ......................................................................................................................33 6.10 DIRECT ACCESS TO SOURCE DATA/DOCUMENTS ............................................................33 6.11 QUALITY CONTROL AND QUALITY ASSURANCE..............................................................33 6.12 ETHICS.............................................................................................................................33 6.13 DATA HANDLING AND RECORD KEEPING........................................................................34 6.14 FINANCING AND INSURANCE ...........................................................................................34 6.15 PUBLICATION POLICY......................................................................................................34 6.16 SUPPLEMENTS..................................................................................................................34 7. INVESTIGATORÍS BROCHURE.....................................................................................34 7.1 INTRODUCTION................................................................................................................34 7.2 GENERAL CONSIDERATIONS............................................................................................35 7.3 CONTENTS OF THE INVESTIGATORÍS BROCHURE...................................................................35 7.5 APPENDIX 2:.................................................................................................................38 8. ESSENTIAL DOCUMENTS FOR THE CONDUCT OF A CLINICAL TRIAL.........39 8.1 INTRODUCTION................................................................................................................39 8.2 BEFORE THE CLINICAL PHASE OF THE TRIAL COMMENCES .............................................40 8.3 DURING THE CLINICAL CONDUCT OF THE TRIAL .............................................................44 8.4 AFTER COMPLETION OR TERMINATION OF THE TRIAL.....................................................48 © EMEA 2006 4 INTRODUCTION Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects. Compliance with this standard provides public assurance that the rights, safety and well-being of trial subjects are protected, consistent with the principles that have their origin in the Declaration of Helsinki, and that the clinical trial data are credible. The objective of this ICH GCP Guideline is to provide a unified standard for the European Union (EU), Japan and the United States to facilitate the mutual acceptance of clinical data by the regulatory authorities in these jurisdictions. The guideline was developed with consideration of the current good clinical practices of the European Union, Japan, and the United States, as well as those of Australia, Canada, the Nordic countries and the World Health Organization (WHO). This guideline should be followed when generating clinical trial data that are intended to be submitted to regulatory authorities. The principles established in this guideline may also be applied to other clinical investigations that may have an impact on the safety and well-being of human subjects. 1. GLOSSARY 1.1 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 product 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 response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of diseases or for modification of physiological function (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting). 1.2 Adverse Event (AE) Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product (see the ICH Guideline for Clinical Safety Data Management: Definitions and Standards for Expedited Reporting). 1.3 Amendment (to the protocol) See Protocol Amendment. 1.4 Applicable Regulatory Requirement(s) Any law(s) and regulation(s) addressing the conduct of clinical trials of investigational products. 1.5 Approval (in relation to Institutional Review Boards) The affirmative decision of the IRB that the clinical trial has been reviewed and may be conducted at the institution site within the constraints set forth by the IRB, the institution, Good Clinical Practice (GCP), and the applicable regulatory requirements. 1.6 Audit A systematic and independent examination of trial related activities and documents to determine whether the evaluated trial related activities were conducted, and the data were recorded, © EMEA 2006 5 ... - tailieumienphi.vn