HANDBOOK OF SOPs FOR GOOD CLINICAL PRACTICE

SECOND EDITION

Celine M. Clive

Interpharm /CRC
Boca Raton London New York Washington, D.C.
2004 by CRC Press LLC

Library of Congress Cataloging-in-Publication Data

Clive, Celine. Handbook of SOPs for good clinical practice.2nd ed. / Celine Clive. p. ; cm. Rev. ed. of: A handbook of SOPs for good clinical practice / Donald E. Maynard, B. Joyce Baird. c1996. Includes bibliographical references and index. ISBN 0-8493-2181-6 1. Clinical trialsStandardsHandbooks, manuals, etc. 2. Clinical trialsForms Handbooks, manuals etc. [DNLM: 1. ResearchstandardsHandbooks. 2. Clinical TrialsstandardsHandbooks. 3. Human ExperimentationstandardsHandbooks. 4. Legislation, DrugHandbooks. W 49 C642h 2004] I. Title: Handbook of standard operating procedures for good clinical practice. II. Maynard, Donald E. Handbook of SOPs for good clinical practice. III. Title.] R853.C55C585 2004 610.724dc22

2003064123

This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microlming, and recording, or by any information storage or retrieval system, without prior permission in writing from the publisher. The consent of CRC Press LLC does not extend to copying for general distribution, for promotion, for creating new works, or for resale. Specic permission must be obtained in writing from CRC Press LLC for such copying. Direct all inquiries to CRC Press LLC, 2000 N.W. Corporate Blvd., Boca Raton, Florida 33431. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identication and explanation, without intent to infringe.

Visit the CRC Press Web site at www.crcpress.com

2004 by CRC Press LLC No claim to original U.S. Government works International Standard Book Number 0-8493-2181-6 Library of Congress Card Number 2003064123 Printed in the United States of America 1 2 3 4 5 6 7 8 9 0 Printed on acid-free paper

2004 by CRC Press LLC

Dedication
The author gratefully dedicates this book to Patrick and Josephine Meehan for their continuous support and encouragement, and for providing an example to follow in life. Celine M. Clive

2004 by CRC Press LLC

Introduction
This handbook is divided into three sections containing Standard Operating Procedures (SOPs) applicable to the activities of the three major groups involved in the clinical development process: The Sponsor/Contract Research Organization (CRO) The study site The Institutional Review Board (IRB)

A fourth section, called Forms, contains all of the attachments that are referred to in the SOP sections. Some of the forms may apply to more than one group affected by the SOPs. For example, the Subject Information and Consent Form Checklist may be used by Study Coordinators, when they are developing the document, and IRB members, when they are reviewing it. The advantage of this handbook is that by using the material found on the CRC Web site: www.crcpress.com/e_products/downloads/download.asp, each SOP and all of the forms can be customized to the needs of the specific institution. To do this, the user should open the document and make a global change replacing the word Company with the companys actual name. Be aware that the length of the companys name may affect line and page spacing and that some minor formatting may be needed after this global change is implemented. If the institutions logo is added to the header of the first page, the formatting may also need to be checked. Finally, the effective date should be added to the header of the second page. From there, it will automatically be captured on all subsequent pages. These templates should serve as a starting point for the development of SOPs. The user should ensure that the specific processes at his/her institution are reflected in the final, approved SOP. The language in these SOPs may appear to be limited to drug development; however, with a few alterations, they may be adapted to medical devices and biologics as well.

2004 by CRC Press LLC

About Polaris Clinical Research Consultants, Inc.

Polaris Clinical Research Consultants, Inc. is a training and auditing company specializing in
clinical research topics and processes. Our mission is to enhance the productivity and efficiency of clinical research teams by providing training, auditing, and Standard Operating Procedure (SOP) development to our clients.

Polaris

offers consulting services to pharmaceutical companies, Contract Research Organizations (CRO), investigative sites, and Institutional Review Boards (IRBs). The company offers several off-the-shelf training programs for Monitors, Investigators, Study Coordinators, and IRB Members. Because we are interested in establishing collaborative relationships with our clients, more often our training programs are customized to the specific needs of our clients. We recognize the demand for experienced professionals exceeds the supply and we believe that through training we can help bridge that gap. Some of the advantages of using Polaris include: Active participation of the learners. Polaris training programs are delivered through exercises, case studies, role-playing, and worksheets. This active involvement by the participant ensures that the lessons become more intrinsic and the learning becomes more effective. Experienced personnel. Polaris training programs are developed and delivered by experts in various areas of the pharmaceutical industry. This provides students with high quality training that is realistic and practical. Program flexibility. Polaris training is delivered so that the point-of-view and needs of both the CRO and Sponsor company are discussed. Programs to investigative sites include discussions on what site personnel are required to do by regulation and which tasks are driven by Sponsor-specific requirements.

Celine M. Clive Polaris Clinical Research Consultants, Inc. 130 Iowa Lane; Suite 103 Cary, NC 27511 Telephone: 919-463-0003 Fax: 919-463-0004 E-mail: CMClive@AOL.com

2004 by CRC Press LLC

Programs Available through Polaris Overview of Drug Development Overview of Clinical Research History of the Regulations FDA Structure and Processes Regulations that Affect Clinical Research (FDA and ICH) The Responsibilities of Sponsors, Monitors, and Site Personnel The Responsibilities of Contract Research Organizations The Role of the Institutional Review Board Preparing Documents for Study Initiation Selecting Investigators and Study Sites Developing Protocols and Case Report Forms Conducting the Study Initiation Visit Developing and Obtaining Informed Consent Conducting the Interim Visit Adverse Experiences and Serious Adverse Experiences Editing Case Report Forms Interacting with the Study Coordinator Reviewing Regulatory Documents Case Report Form Tracking and Management Managing Clinical Trial Material/Drug Accountability Writing Trip Reports and Follow-Up Letters Role of Data Management in the Clinical Research Process Safety When Traveling Writing Protocols Designing Case Report Forms FDA Audits Detecting Fraud in Clinical Research

2004 by CRC Press LLC

Table of Contents
Sponsor/Monitor/CRO SOPs MON-001.0 MON-002.0 MON-003.0 MON-004.0 MON-005.0 MON-006.0 MON-007.0 MON-008.0 MON-009.0 MON-010.0 MON-011.0 MON-012.0 MON-013.0 Preparation, Issue, and Revision of Standard Operating Procedures (SOPs) Training Clinical Research Staff Selecting Investigators and Study Sites Developing Informed Consent Forms Conducting Site Evaluation Visits Conducting Study Initiation Visits Conducting Periodic Site Visits Reviewing Case Report Forms at the Study Site Reviewing Regulatory Documents Adverse Experiences (AEs), Serious Adverse Experiences (SAEs), and IND Safety Reports Managing Study-Specific Clinical Supplies Conducting Study Termination Visits Telephone Contact Reports Investigational Site SOPs SITE-001.0 SITE-002.0 SITE-003.0 SITE-004.0 SITE-005.0 SITE-006.0 SITE-007.0 SITE-008.0 SITE-009.0 SITE-010.0 SITE-011.0 Preparation, Issue, and Revision of Standard Operating Procedures (SOPs) Training Study Site Clinical Research Staff Assessing Protocol Feasibility Investigator Agreements with Sponsors or Contract Research Organizations Organizational Chart for the Study Site Interactions with the Institutional Review Board Recruiting Study Patients Study Initiation and Implementation Reviewing and Obtaining Informed Consent Adverse Experiences (AEs), Serious Adverse Experiences (SAEs) and IND Safety Reports Drug Storage and Accountability

2004 by CRC Press LLC

SITE-012.0 SITE-013.0 SITE-014.0

Managing Biological Samples Interactions with the Sponsor or Contract Research Organization (CRO) Study Files and Record Retention Institutional Review Board SOPs

IRB-001.0 IRB-002.0 IRB-003.0 IRB-004.0 IRB-005.0 IRB-006.0 IRB-007.0 IRB-008.0 IRB-009.0

Institutional Review Board Responsibilities IRB Membership and Training Institutional Review Board Meetings IRB Record Keeping IRB Review of Research IRB Review of Informed Consent IRB Review of Advertisements IRB Review of Unscheduled Mandatory Reports Criteria for Exempt and Expedited Review Forms Alphabetical by File Name

File Name (.doc) Ad Review Amendment Bio Sample CRF Review DCF Form Dispense Dispense by Pt Drug Disposition Drug Order Drug Receipt Drug Return Enrollment Expedited ICF Review Init Doc Track

Form Name Advertisement Review Checklist Protocol Amendment Form Biological Samples Inventory CRF Review Form Data Clarification Form Drug Dispensing Log Study Subject Investigational Product Dispensing Record Clinical Trial Materials Disposition Form Investigational Drug Shipping Order Investigational Product Receipt Form Drug Return Form Screening and Enrollment Log Expedited Review Form Subject Information and Consent Form Checklist Study Initiation Document Tracking Worksheet

2004 by CRC Press LLC

Initial Sub IRB Member Minutes Template Monitor Log Patient Master Phone Rpt Progress Rpt Responsibilities Review Cklist Review Results SAE Safety Rpt Sig Sheet St Term Ack St Term Notice Training Plan Training Record Training Request Training Verification Trip Rpt Evaluation Trip Rpt Init Trip Rpt Interim Trip Rpt Termination

Initial Submission Form IRB Membership Roster IRB Meeting Minutes Template Monitoring Log Master Subject Log Telephone Contact Report IRB Progress Report Form Study Responsibilities Form Reviewers Checklist IRB Review Results Form Serious Adverse Experiences Safety Information Form Study Site Personnel Signature Sheet IRB Study Termination Acknowledgement IRB Notification of Study Termination Form Training Plan Form Training Record Form Staff Training Request Form Staff Training Verification Form Site Evaluation Visit Trip Report Study Initiation Visit Trip Report Periodic Site Visit Trip Report Study Termination Visit Trip Report

2004 by CRC Press LLC