Practical Guide to Clinical Data Management, 4th Edition
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Practical Guide to Clinical
Data Management
Fourth Edition
Susanne Prokscha
Front cover image: Micolas/Shutterstock
Fourth edition published 2025
by CRC Press
2385 Executive Center Drive, Suite 320, Boca Raton, FL 33431
and by CRC Press
4 Park Square, Milton Park, Abingdon, Oxon, OX14 4RN
© 2025 Susanne Prokscha
First Edition published in 1999
Second Edition published in 2007
Third Edition published in 2011
CRC Press is an imprint of Taylor & Francis Group, LLC
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Library of Congress Cataloging‑in‑Publication Data
Names: Prokscha, Susanne, author.
Title: Practical guide to clinical data management / by Susanne Prokscha,
Consultant, San Mateo, CA.
Description: [4th edition]. | Boca Raton : CRC Press, 2024. |
Includes bibliographical references and index.
Identifiers: LCCN 2023057462 (print) | LCCN 2023057463 (ebook) |
ISBN 9781032495583 (hardback) | ISBN 9781032498232 (paperback) |
ISBN 9781003395621 (ebook)
Subjects: LCSH: Drugs—Testing—Data processing. | Clinical trials—Data processing. |
Database management.
Classification: LCC RM301.27 .P76 2024 (print) | LCC RM301.27 (ebook) |
DDC 615.1072/4—dc23/eng/20240404
LC record available at https://lccn.loc.gov/2023057462
LC ebook record available at https://lccn.loc.gov/2023057463
ISBN: 978-1-032-49558-3 (hbk)
ISBN: 978-1-032-49823-2 (pbk)
ISBN: 978-1-003-39562-1 (ebk)
DOI: 10.1201/ 9781003395621
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by Apex CoVantage, LLC
Access the Support Material at: https://resourcecentre.routledge.com/
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Contents
Preface.................................................................................................................... xiii
Acknowledgments.................................................................................................... xv
Common Acronyms ...............................................................................................xvii
Introduction to Clinical Trials ............................................................................... 1
Testing in Humans................................................................................1
Clinical Trial Protocols......................................................................... 2
Clinical Trial Process ...........................................................................3
The Importance of Clinical Data Management ....................................5
Regulations, Guidance, and ICH E6 (GCP) .........................................5
PART I Study Startup
Chapter 1 Data Management Plans.......................................................................9
Purpose of Data Management Plans.....................................................9
Contents of the DMP..........................................................................10
Initiating the DMP..............................................................................11
Approving the DMP ...........................................................................12
Revising the DMP ..............................................................................12
Using DMPs with CROs .................................................................... 13
The Value of Data Management Plans ...............................................13
Data Quality and DMPs .....................................................................14
SOPs for DMPs ..................................................................................14
Chapter 2 CRF Design Considerations ............................................................... 16
Primary Goals of CRF Design ........................................................... 16
Collecting Required Data: Visits, Forms, and Fields ......................... 16
Collecting Analyzable Data................................................................21
Protocol Compliance ..........................................................................27
CRFs Linked to Non-CRF Data .........................................................28
Reuse and Refne CRF Modules ........................................................ 29
Data Quality through CRF Design .....................................................29
SOPs on CRF Design .........................................................................30
v
vi Contents
Chapter 3 Selecting Edit Checks ........................................................................ 32
Identifying Possible Edit Checks .......................................................32
Focus on Critical Variables.................................................................35
Data Validation/Edit Check Specifcations.........................................35
Updating Data Validation Specifcations............................................37
Data Quality through Data Validation ................................................37
SOPs for Data Validation Checks.......................................................37
Chapter 4 EDC Study Build and Release ........................................................... 39
eCRF Build.........................................................................................39
Data Validation/Edit Check Programming .........................................41
EDC Study Testing .............................................................................43
Release to Production.........................................................................45
Change Control ..................................................................................47
Data Quality for eCRFs and Edit Checks...........................................47
SOPs on EDC Build ...........................................................................47
Chapter 5 Planning for Blinded Studies ............................................................. 49
Background on Blinding ....................................................................49
Maintaining the Blind.........................................................................50
Accidental Unblinding .......................................................................52
Unblinded Study Team Members.......................................................52
Blinding Impacts Data Quality...........................................................53
SOPs and Study Plans for Blinding....................................................53
Chapter 6 Patient Reported Outcomes................................................................54
Background to Patient-Reported Outcomes .......................................54
Licensing PRO Questionnaires...........................................................55
Considerations for Electronic Collection ...........................................56
Considerations for Paper Instruments ................................................57
Protocol Compliance ..........................................................................58
Budgeting Time and Money ...............................................................58
Data Quality for ePRO .......................................................................59
SOPs and Study Plans for PROs ........................................................59
PART II Study Conduct
Chapter 7 Overseeing eCRF Data Entry............................................................. 63
Tracking Participants Enrolled ...........................................................63
Forms Entered vs Forms Expected.....................................................64
Tracking Investigator Signatures........................................................65
Contents vii
Monitoring Data Entry Benefts Data Quality....................................66
SOPs and Study Plans for Data Collection........................................66
Chapter 8 Managing Queries ..............................................................................68
System Queries...................................................................................68
Manual Queries ..................................................................................69
Tracking Open Queries....................................................................... 70
Quality Control for Queries................................................................71
Using Queries to Improve Data Quality.............................................71
SOPs and Study Plans for Managing Queries ....................................72
Chapter 9 Collecting Adverse Event Data .......................................................... 73
Collecting AEs and SAEs...................................................................73
Adverse Event Forms ......................................................................... 75
Storing and Cleaning AE Data ...........................................................76
Coding Adverse Event Terms .............................................................77
Reconciling Serious Adverse Events..................................................78
Coding and Reconciliation Approvals................................................80
Data Quality for AEs .......................................................................... 80
SOPs and Study Plans for AE Data....................................................80
Chapter 10 Managing Lab Data............................................................................ 82
Data Management for Lab Data .........................................................82
Lab Test Names ..................................................................................83
Storing Units ......................................................................................83
Lab Reference Ranges ........................................................................ 85
Laboratory Identifcation....................................................................86
Central Labs .......................................................................................87
Using Specialty Labs..........................................................................87
Data Quality for Lab Results..............................................................89
SOPs and Study Plans for Processing Lab Data.................................89
Chapter 11 Receiving Non-CRF Data .................................................................. 90
Receiving Electronic Files from a Vendor..........................................90
Cleaning Non-CRF Data ....................................................................92
Managing Blinded Data......................................................................94
Data Quality for External Data...........................................................94
SOPs and Study Plans for Non-CRF Data ......................................... 95
Chapter 12 Data Review .......................................................................................96
Edit Checks vs Data Review ..............................................................96
Data Review Plan ...............................................................................96
Performing Data Review ....................................................................97
viii Contents
Planning for Manual Queries .............................................................98
Data Quality and Manual Data Reviews ............................................99
SOPs and Study Plans for Data Review .............................................99
Chapter 13 Risk-Based Quality Management of Clinical Trials ........................ 100
Background ......................................................................................100
A Structure for Risk-Based Quality Management ...........................100
Centralized Monitoring ....................................................................105
Working with Clinical Operations....................................................106
RBQM Aids Data Quality ................................................................107
SOPs and Study Plans for RBQM....................................................107
Chapter 14 Managing EDC Changes.................................................................. 108
Change Control for Studies ..............................................................108
eCRF Changes..................................................................................109
Edit Check Changes .........................................................................112
Other Study Changes........................................................................113
Testing and Approval........................................................................113
Impact on Investigator Signatures ....................................................113
Changes Associated with a Protocol Amendment............................114
Maintaining Data Quality during EDC Study Changes ...................115
SOPs for EDC Changes....................................................................115
PART III Study Lock
Chapter 15 Study Lock ....................................................................................... 119
Core Requirements for Study Lock..................................................119
Final Study Lock ..............................................................................123
Interim Study Lock...........................................................................123
Data Extract Plans or Specifcations ................................................124
Soft Lock ..........................................................................................125
Time to Study Database Lock ..........................................................125
Final Data Quality ............................................................................126
SOPs and Study Plans for Study Locks ...........................................127
Chapter 16 After Study Lock.............................................................................. 128
Post-Lock Activities .........................................................................128
Unlocking EDC Studies ...................................................................130
Data Quality and TMF Quality ........................................................132
SOPs and Study Plans for Post-Lock and Unlock............................132
Contents ix
PART IV Necessary Infrastructure
Chapter 17 SOPs for CDM.................................................................................. 135
What Is an SOP?...............................................................................135
SOPs for Data Management .............................................................137
Creating SOPs ..................................................................................138
Complying with SOPs......................................................................140
SOP on SOPs....................................................................................144
Quality through SOP Revisions .......................................................144
Chapter 18 CDM and the TMF........................................................................... 146
TMF Reference Model .....................................................................146
Reviewing the Study Reference Model............................................147
Submitting to the TMF .....................................................................150
TMF QC ...........................................................................................150
Supporting Documents, Email, and NTFs .......................................151
Living with the TMF ........................................................................152
Chapter 19 Training ............................................................................................ 153
Minimum Required Training............................................................153
Training Matrices .............................................................................155
How to Train.....................................................................................156
Training Records ..............................................................................157
Experience and Education ................................................................158
Allotting Time for Training ..............................................................158
SOPs on Training .............................................................................159
Chapter 20 User Management............................................................................. 160
Account Management.......................................................................160
Access Control through Roles..........................................................162
Taking Security Seriously ................................................................163
SOPs and Guidelines for Accounts ..................................................163
Chapter 21 Developing and Using Standards ..................................................... 165
The Goal and Purpose of Standards .................................................165
Industry Standards............................................................................166
Where to Start...................................................................................166
Standards Team Governance ............................................................167
Using Standards................................................................................168
SOPs for Standards...........................................................................169
x Contents
Chapter 22 Working with Service Providers ...................................................... 170
Data Management CROs..................................................................170
The CRO Myth .................................................................................171
Qualifying CROs ..............................................................................171
Defning Responsibilities .................................................................172
Oversight Metrics .............................................................................173
Oversight During the Trial ...............................................................173
Resourcing........................................................................................176
EDC Vendors as CROs .....................................................................177
Functional Service Providers............................................................177
Benefting from CROs......................................................................177
SOPs for Working with CROs..........................................................178
PART V Using Computerized Systems
Chapter 23 Data Integrity ................................................................................... 183
What Is Data Integrity? ....................................................................183
Integrity in the Data Lifecycle..........................................................185
Demonstrating Integrity in Transfers ...............................................187
Applying Risk Assessments .............................................................188
Chapter 24 Data in EDC Systems....................................................................... 189
Control of Data: Hosting ..................................................................189
Data Entry by the Sponsor or CRO ..................................................190
Need for Data Repositories ..............................................................191
Chapter 25 Choosing Vendor Systems................................................................ 192
Defning Business Needs..................................................................192
Initial Data Gathering.......................................................................193
Extended Demos and Pilots..............................................................195
Additional Considerations................................................................196
What Is Missing?..............................................................................198
Qualifying a Vendor .........................................................................198
Preparing for Implementation ..........................................................199
Chapter 26 Implementation Planning .................................................................200
Overview and Related Plans.............................................................200
Essential Preparation ........................................................................201
Validation .........................................................................................201
Integration and Extensions ...............................................................202
Contents xi
Migration of Legacy Data ................................................................202
Benefting from Pilots ......................................................................203
Assessing SOPs and Other Documents ............................................204
Preparation for Production ...............................................................204
Successful Implementation...............................................................205
Chapter 27 System Validation.............................................................................206
What Is System Validation?..............................................................206
Systems That Require Validation .....................................................207
Validation for Hosted Systems .........................................................207
Validation Plan .................................................................................208
Validation Testing.............................................................................208
Validation Report..............................................................................212
Change Control ................................................................................212
Requirements and Benefts...............................................................213
Chapter 28 Migrating and Archiving Data ......................................................... 214
Regulatory Expectations...................................................................214
When to Migrate...............................................................................215
EDC Migrations ...............................................................................216
Complex Migrations.........................................................................216
Migration by Re-Entry .....................................................................217
Audit Trails in Migrations ................................................................217
Archiving and Decommissioning.....................................................218
Migration and Archive Plans ............................................................219
Data Integrity for Migrations and archiving.....................................219
Chapter 29 EDC Study Rebuilds ........................................................................ 221
Circumstances Leading to Rebuilds .................................................221
eCRF and Edit Check Rebuild .........................................................222
Moving Data.....................................................................................222
Investigator Signatures .....................................................................224
Integrated Systems ...........................................................................224
Site Impact........................................................................................225
Documentation .................................................................................225
Appendix A: Data Management Plan Outline .................................................. 227
Appendix B: Data Extract Plan Example.......................................................... 233
Appendix C: System Implementation Outline .................................................. 243
Index......................................................................................................................245
Preface
Clinical Data Management’s importance has continued to grow since I wrote the frst
version of this book in 1998. I wanted to fll a need for reference material for the
growing number of clinical data managers who saw their work as a profession. This
latest is long overdue given the tremendous changes that have taken place (and are
still taking place) since the previous edition was released in 2012. The industry, reg-
ulatory environment, and technology used in clinical data management have changed
so much in the intervening years that this edition is a nearly complete rewrite.
As I complete this manuscript, ICH E6 (R3), Good Clinical Practice, has been
released in draft for the consultation period. Because we do not know when the fnal
version of E6 will be released, and because of the strong interest in this new edition
of the book, I have decided to publish this edition based on draft language from E6.
A list of updates will be available at the publisher’s website https://resourcecentre.
routledge.com/books/9781032495583 soon after E6 (R3) is adopted by the ICH and
these may be incorporated into a minimal revision to follow.
A few topics found in the 3rd edition no longer seem important, leading to the
removal of entire sections and even chapters (e.g., the discussion of coding diction-
aries). Some newer topics have gained in importance enough to justify new chapters
(e.g., risk-based quality management, data integrity, patient reported outcomes). All
discussion of paper-based data collection has been removed, except in the patient
reported outcomes chapter.
There is always more that could be said about each topic, but I have kept to the
philosophy of the frst edition, which was to provide the most critical information
that impacts data management and clinical trial conduct. Throughout, I have kept
the information practical rather than academic in the hopes that it can be applied by
every reader to every CDM group, and that non-data managers will also beneft from
understanding how the process of collecting and managing clinical data impacts the
success and value of a trial.
xiii
Acknowledgments
Appreciation to those who supported this edition.
My sincere thanks to Clarice Grant Coles, whose support and feedback helped
keep my confdence up through the writing of this edition. Her “Yes! This!” com-
ments in the manuscript did more for me than she realizes. Examples from Clarice’s
varied career in data management have found their way into several chapters.
Thanks also to Rob Rittberg and OpenClinica for providing me access to
OpenClinica’s EDC platform. When I frst reached out in an email to Rob to ask
if we could arrange something, he delighted me by replying with a photo of him-
self holding the previous edition of this book. Access to OpenClinica allowed me to
obtain screenshots from an EDC system to enhance discussion of eCRF development
and data capture.
I consider myself incredibly fortunate to still have my mother, Barbara Prokscha,
to support me, both in writing this book and in life.
xv
