Một cuốn sách hay về thử nghiệm lâm sàng. Cuốn sách nói về các chủ đề: 1. Quá trình phát triển thuốc, sinh phẩm và thiết bị y khoa 2. Thực hành tốt lâm sàng và các quy định 3. Bản đồng thuận tham gia nghiên cứu 4. Ủy ban xét duyệt nội bộ 5. Tác dụng phụ khi sử dụng thuốc Sách tiện làm tài liệu tham khảo cho sinh viên chuyên ngành y dược
9781405195157_1_pre.qxd 11/16/09 16:03 Page iii A Clinical Trials Manual from the Duke Clinical Research Institute Lessons From A Horse Named Jim Second Edition Margaret B Liu Principal, Clinical Trials Consulting Singapore (Formerly Manager of the Monitoring Group at the Duke Clinical Research Institute, Durham, North Carolina, USA) and Kate Davis Clinical Research Communications Specialist Duke Clinical Research Institute Durham, North Carolina, USA A John Wiley & Sons, Ltd., Publication 9781405195157_1_pre.qxd 11/16/09 16:03 Page iv 9781405195157_1_pre.qxd 11/16/09 16:03 Page i A Clinical Trials Manual from the Duke Clinical Research Institute 9781405195157_1_pre.qxd 11/16/09 16:03 Page ii “Somewhere, something incredible is waiting to be known.” Carl Sagan (1934–1996) American astronomer, astrochemist, and author 9781405195157_1_pre.qxd 11/16/09 16:03 Page iii A Clinical Trials Manual from the Duke Clinical Research Institute Lessons From A Horse Named Jim Second Edition Margaret B Liu Principal, Clinical Trials Consulting Singapore (Formerly Manager of the Monitoring Group at the Duke Clinical Research Institute, Durham, North Carolina, USA) and Kate Davis Clinical Research Communications Specialist Duke Clinical Research Institute Durham, North Carolina, USA A John Wiley & Sons, Ltd., Publication 9781405195157_1_pre.qxd 11/16/09 16:03 Page iv This edition first published 2010, © 2010 by Duke Clinical Research Institute Blackwell Publishing was acquired by John Wiley & Sons in February 2007 Blackwell’s publishing program has been merged with Wiley’s global Scientific, Technical and Medical business to form Wiley-Blackwell Registered office: John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK Editorial offices: 9600 Garsington Road, Oxford, OX4 2DQ, UK The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK 111 River Street, Hoboken, NJ 07030-5774, USA For details of our global editorial offices, for customer services 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owners The publisher is not associated with any product or vendor mentioned in this book This publication is designed to provide accurate and authoritative information in regard to the subject matter covered It is sold on the understanding that the publisher is not engaged in rendering professional services If professional advice or other expert assistance is required, the services of a competent professional should be sought The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should not be relied upon as recommending or promoting a specific method, diagnosis, or treatment by physicians for any particular patient The publisher and the author make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of fitness for a particular purpose In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions Readers should consult with a specialist where appropriate The fact that an organization or Website is referred to in this work as a citation and/or a potential source of further information does not mean that the author or the publisher endorses the information the organization or Website may provide or recommendations it may make Further, readers should be aware that Internet Websites listed in this work may have changed or disappeared between when this work was written and when it is read No warranty may be created or extended by any promotional statements for this work Neither the publisher nor the author shall be liable for any damages arising herefrom Library of Congress Cataloging-in-Publication Data Liu, Margaret B A clinical trials manual from the Duke Clinical Research Institute : lessons from a horse named Jim / Margaret B Liu and Kate Davis – 2nd ed p ; cm Rev ed of: Lessons from a horse named Jim / by Margaret B Liu and Kate Davis c2001 Includes bibliographical references and index ISBN 978-1-4051-9515-7 Clinical trials–Handbooks, manuals, etc Drugs–Testing–Handbooks, manuals, etc I Davis, Kate (Kate G.) II Liu, Margaret B Lessons from a horse named Jim III Duke Clinical Research Institute IV Title [DNLM: Clinical Trials as Topic–legislation & jurisprudence–United States Clinical Trials as Topic–ethics–United States Device Approval–United States Drug Approval–United States QV 733 AA1 L783c 2010] R853.C55L58 2010 615.5072′4–dc22 2009020427 A catalogue record for this book is available from the British Library Set in 10/13pt Rotis SemiSans by Graphicraft Limited, Hong Kong Printed and bound in Singapore 2010 9781405195157_1_pre.qxd 11/16/09 16:04 Page v Contents Contents Foreword by Robert A Harrington Preface List of Abbreviations Lessons from a Horse Named Jim and Other Events in History Affecting the Regulation of Clinical Research The Process: Developing New Drugs, Biologics, and Devices The Drug Development Process Background Information Pre-Clinical Studies The Investigational New Drug Application Clinical Trial Phases Application to Market New Drugs and Biologics FDA Review Groups Early or Expanded Access to Unapproved Drugs and Biologics Orphan Drugs Developing New Devices Background Information What is a Medical Device? Medical Device Classification Requirements for Marketing New Devices Humanitarian Use Devices Early or Expanded Access to Unapproved Medical Devices FDA Device Review Combination Products Postmarketing Surveillance of Drugs, Biologics, and Devices Phase Postmarketing Drug and Biologics Studies Phase Postmarketing Device Studies Direct Reporting Based on Observations Good Clinical Practice and the Regulations Good Clinical Practice Regulations xiii xv xviii 13 14 14 15 16 17 20 21 24 25 26 27 28 29 33 36 36 38 38 39 40 40 41 49 50 50 v 9781405195157_1_pre.qxd 11/16/09 16:04 Page vi Guidelines Local Laws Responsibilities in the Code of Federal Regulations Principal Investigator Responsibilities Institutional Review Board Responsibilities Sponsor Responsibilities Sponsor-Investigators Where to Obtain Information and Guidance for the Regulations and GCP The Federal Register FDA Guidance Documents Online Resources vi Informed Consent and the Regulations What Is Informed Consent? Ethical Codes Regarding Informed Consent The Belmont Report: Application of Respect for Persons The Declaration of Helsinki The Nuremberg Code Regulatory Requirements for Informed Consent General Requirements for Informed Consent (21 CFR 50.20) Exceptions from the General Requirements (21 CFR 50.23) Exceptions from Informed Consent Requirements for Emergency Research (21 CFR 50.24) Elements of Informed Consent (21 CFR 50.25) Documentation of Informed Consent (21 CFR 50.27) Consent from Vulnerable Subjects HIPAA/Privacy Rule Requirements The Informed Consent Process Writing the Consent Form Obtaining Informed Consent Documenting Informed Consent Continuing Informed Consent Institutional Review Boards What is an Institutional Review Board? Types of IRBs IRB Membership IRB Activities Reviewing Research Reporting Unanticipated Problems Involving Risks to Subjects or Others 59 60 62 62 67 68 70 70 70 71 71 73 74 75 75 76 77 77 78 79 79 80 82 85 90 92 92 95 96 97 101 102 103 104 107 107 109 11/16/09 16:04 Page vii Establishing Written Procedures Types of IRB Review Full Committee Review Expedited Review Items That Must be Submitted for IRB Review Exemptions: When IRB Approval Is Not Required Continuing Review after Initial Study Approval Review of Adverse Events and Unanticipated Problems Communication between IRBs and Investigators Investigator Notification of the Outcome of IRB Review Communication During Study IRB Notification at Study Completion Communication between IRBs and Study Sponsors IRB Records and Reports Accreditation of IRBs Registration Adverse Events and Unanticipated Problems Involving Risks to Subjects or Others Why Collect Adverse Event Data? Safety Profile Benefits and Risks Evaluation Package Insert Adverse Events Internal and External Adverse Events Serious Adverse Events Unanticipated Problems Involving Risks to Subjects or Others Investigator Responsibilities Collecting Adverse Event Data Reporting Adverse Event Data Expedited Reporting of Adverse Events Reporting Unanticipated Problems Involving Risks to Subjects or Others Reporting Unanticipated Adverse Device Effects IRB Responsibilities Review and Reporting of Serious Adverse Events Review and Reporting of Unanticipated Problems Sponsor Responsibilities Expedited Reporting in Drug Trials Expedited Reporting in Device Trials Routine Reporting by Sponsors 110 111 111 112 113 113 114 Contents 9781405195157_1_pre.qxd 115 116 116 116 117 117 118 119 120 123 124 125 125 125 125 126 126 127 129 129 130 131 133 135 135 135 136 136 137 138 139 vii ... (Formerly Manager of the Monitoring Group at the Duke Clinical Research Institute, Durham, North Carolina, USA) and Kate Davis Clinical Research Communications Specialist Duke Clinical Research Institute. .. Cataloging-in-Publication Data Liu, Margaret B A clinical trials manual from the Duke Clinical Research Institute : lessons from a horse named Jim / Margaret B Liu and Kate Davis – 2nd ed p ; cm Rev ed of: Lessons from. .. Principal, Clinical Trials Consulting Singapore (Formerly Manager of the Monitoring Group at the Duke Clinical Research Institute, Durham, North Carolina, USA) and Kate Davis Clinical Research