Second Edition
Patrick Waller
Formerly Honorary Professor,
London School of Hygiene and Tropical Medicine,
London, United Kingdom
Mira Harrison‐Woolrych
Honorary Research Associate Professor,
Dunedin School of Medicine, University of Otago,
New Zealand; Senior Medical Assessor, Vigilance and Risk
Management, Medicines and Healthcare products Regulatory
Agency (MHRA), London, United Kingdom and Secretary General
of the International Society of Pharmacovigilance (ISoP)
This edition first published 2017. © 2017 John Wiley & Sons Ltd
First edition published 2010 by John Wiley & Sons Ltd
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Library of Congress Cataloging‐in‐Publication Data
Names: Waller, Patrick, 1957 January 30– author. | Harrison‐Woolrych, Mira, author.
Title: An introduction to pharmacovigilance / Patrick Waller, Mira Harrison‐Woolrych.
Description: 2nd edition. | Chichester, West Sussex, UK ; Hoboken, NJ : John Wiley & Sons Inc., [2017] | Includes bibliographical references and index.
Identifiers: LCCN 2016059298| ISBN 9781119289746 (pbk.) | ISBN 9781119289753 (Adobe PDF) | ISBN 9781119289784 (epub)
Subjects: | MESH: Pharmacovigilance | Drug Monitoring–methods | Drug‐Related Side Effects and Adverse Reactions | Pharmaceutical Preparations–standards
Classification: LCC RM302.5 | NLM QV 771 | DDC 615/.7042–dc23
LC record available at https://lccn.loc.gov/2016059298
A catalogue record for this book is available from the British Library.
Cover Design: Wiley
Cover Credit: © Jorg Greuel/Gettyimages
The book is dedicated to the memory of the late Dr Susan M. Wood, an inspirational person who worked tirelessly in the field of pharmacovigilance for 10 years before her premature death in 1998.
Patrick Waller was an Honorary Professor at the London School of Hygiene and Tropical Medicine 2011–2016 and Chair of the Independent Scientific Advisory Committee (ISAC) for Medicines and Healthcare products Regulatory Agency (MHRA) database research 2012–2016. He graduated in medicine in Sheffield, and then trained in clinical pharmacology and public health. Subsequently he worked at the Drug Safety Research Unit in Southampton and the Medicines Control Agency in London. He was Chairman of the EU Pharmacovigilance Working Party 1998–2000 and an independent consultant in pharmacovigilance and pharmacoepidemiology 2002–2011.
Mira Harrison‐Woolrych is an Honorary Research Associate Professor at the Dunedin School of Medicine, University of Otago. With a background in clinical obstetrics and gynaecology, she has over 20 years’ experience in pharmacovigilance in both the UK and New Zealand. She is currently Secretary General of the International Society of Pharmacovigilance (ISoP). As a Senior Medical Assessor at the UK MHRA, Mira specialises in women’s medicines and in 2015 edited the textbook Medicines for Women. Between 2003 and 2013, she was the Director of the NZ Intensive Medicines Monitoring Programme (IMMP) and has an extensive list of pharmacoepidemiology research publications. She has also served on several national and international pharmacovigilance committees.
No effective medicine is without risk, and full understanding of a medicine’s safety profile is only achieved after wide clinical use. The advent of new therapies which hold the promise of transforming disease outlook means that patients and healthcare professionals are unwilling to wait to access them. It also means that the uncertainties around the balance of benefits and risks at the time of first availability of a new medicine may be greater than ever.
With every therapeutic advance, the boundaries between categories of healthcare products – medicines, advanced therapies, diagnostic agents – become ever more blurred and the practice of medicine more personalised to the individual patient. The continuing need for the study of medicines safety in wider populations could perhaps be called into question.
In fact, the study of drug safety in clinical use has moved to centre stage in public health, precisely because of the recognition that although by and large adverse effects are rare, it is only by undertaking systematic large‐scale surveillance that we can detect serious problems early and take prompt action to minimise harms – as it were, to ‘fix it while you fly’.
Pharmaceuticals are used internationally and the need for effective drug safety monitoring is recognised worldwide. A signal of a safety issue associated with a new medicine introduced in a public health programme in a resource‐limited setting is just as relevant to a patient who may receive the same medicine in a high‐tech healthcare environment. The political landscape may shift, but pharmacovigilance knows no borders.
The detection and evaluation of adverse effects associated with medicines involves specialists from a range of scientific disciplines who are attracted by the challenges of adding new knowledge that supports safe use of medicines. But pharmacovigilance can only be effective if it is relevant to the daily lives and embedded in the professional practice of all those who use medicines – the prescriber, the patient and their carer. There is clear evidence that reports from patients provide invaluable information on the impact of an adverse effect on life and work, and are of an equivalent level of seriousness to those from healthcare professionals.
This all adds up to the value of a broad appreciation and an up‐to‐date understanding of the principles and practice of pharmacovigilance. This new edition of a clear and succinct yet comprehensive guide to the field provides exactly the right introduction for those new to the challenges and the excitement of pharmacovigilance. It conveys the importance to public health protection of an effective safety net to pick up new information, and the need for well‐planned strategies to generate new evidence as an enabler of innovation.
Everyone who uses a medicine has a part to play in helping to fill the knowledge gaps on safety in as near to real‐time as possible. While pharmacovigilance has now moved on to more robust forms of evidence than reliance on individual case reports of adverse effects, the alert prescriber or patient who observes a possible link between a medicine they are using and an adverse effect is still the cornerstone of pharmacovigilance. The appreciation that each one of us has a role in drug safety means that this updated book is not only a welcome but an essential guide.
The general aim of this book – to provide a brief and broad introduction for newcomers to the field which can be read through in a few hours – has not changed since publication of the first edition in early 2010. In this second edition, we have updated every chapter to reflect pharmacovigilance practice in mid‐2016 and have also broadened its international scope. Pharmacovigilance today is a global activity and our aim is to provide a short introduction relevant to readers worldwide. In response to feedback received on the first edition, we have added a new chapter on clinical aspects of pharmacovigilance (Chapter 7), which we hope will help readers without a medical background understand the importance of drug safety in ‘real life’. For reference, we have added a list of all the abbreviations used in the book and we have also considerably expanded the glossary.
All scientific books are at risk of rapidly becoming out of date. When this one was first published, major changes in the landscape of regulatory pharmacovigilance were already in progress, particularly in the European Union (EU). During the intervening years, these changes have come into force and bedded down (see Chapter 5). In June 2016, the UK electorate voted to leave the EU and the full implications of ‘Brexit’ are not yet clear. However, the need for international collaboration in pharmacovigilance will not diminish and we expect that the worldwide networks discussed in Chapter 6 will be more important than ever before.
We hope that the new edition of this book will prove useful to those entering this interesting and important field. Life may have moved on, but the challenges involved in monitoring the safety of medicines – and taking effective action to protect patients from harm – remain as great as ever.
Everyone knows that safety is important but, apart from a few people whose job it is to oversee safety, this is probably something that most people have at the back of their minds for most of the time. There are likely to be two reasons for this – first, safety is about something adverse not happening (and we tend to be more concerned about things which are happening) and, secondly, it seems to be human nature to think that ‘it will not happen to me’, perhaps as a mechanism for coping with potential threat of something devastating.
The past decade has seen a marked rise in the numbers of people working in the field of clinical drug safety or pharmacovigilance, mostly in the pharmaceutical industry. The trend seems likely to continue, hopefully reflecting a greater focus on the safety of medicines. This book is specifically targeted at newcomers to the field who, of necessity, are often narrowly focused, and it aims to provide them with a brief and broad introduction to the field. My purpose here is to aid rapid understanding of the environment and key principles of pharmacovigilance at the industry–regulatory interface.
My background is in regulation and my experience is of the UK and EU systems and I readily acknowledge these inherent biases in my narrative. This book probably will not help the newcomers with detailed day‐to‐day aspects of their job but I hope it will enable them to see where they fit into a bigger picture. I have assumed that readers will at least have a science degree but not necessarily much specific knowledge about drugs.
The new entrant needs to know how we got where we are today. The most important historical drug safety issues have shaped the development of pharmacovigilance and I have therefore used these as a starting point. I hope that the book will also help the newcomers to appreciate that they are now working in an interesting and important field that is likely to develop much in the near future.
I have deliberately not included any reference citations within the text since, initially, I hope the reader will want to read on rather than go elsewhere. Ample references can be found in the larger texts on to which the reader should next move. In the last chapter, I have selectively cited some important sources that might usefully be consulted for further reading. A glossary defining key terms is provided at the end for reference.
We are most grateful to Ian Boyd and Nourieh Hoveyda who provided valuable comments on the whole redrafted manuscript for this edition. We are also grateful to the following people for review of specific chapters and useful suggestions: Priya Bahri, Keith Beard, Stephen Evans, Valerie Joynson, Marie Lindquist, Julie Williams and Jonathan Woolrych. We would also like to thank the Medicines and Healthcare products Regulatory Agency for providing data from the Yellow Card scheme.