Elizabeth B. Andrews PhD, MPH, FISPE, Vice President, Pharmacoepidemiology and Risk Management,RTI Health Solutions, Research Triangle Park, NC, USANicholas Moore MD, PhD, FRCP(Edin), FISPE, Professor of Clinical Pharmacology, Service Hospitalo-Universitaire de Pharmacologie, Bordeaux, France

• Contributors xiForeword xxi1 Introduction: Updated from Second Edition 1Ronald D. Mann and Elizabeth B. Andrews2 History of Pharmacovigilance 11Judith K. Jones and Elyse KingeryI The Regulatory Basis Of Pharmacovigilance3 Legal Basis: European Union 27Brian Edwards, Calvin Johnson, and Shelley Gandhi4 Ethical Oversight, Consent, and Confi dentiality 37Suzanne L. West and Wendy A. Visscher5 Pharmacovigilance-Related Topics at the Level of the International Conference on Harmonisation 47Priya Bahri6 The Council for International Organizations of Medical Sciences Working Groups and Their Contributions to Pharmacovigilance 63Gunilla Sjölin-Forsberg and William Gregory7 Terminologies in Pharmacovigilance 77 Elliot Brown and Daniel von Sydow8 Nonclinical Toxicological Support for Phase I Trials 95David R. Jones and James W. MCBlane9 The Evaluation of Adverse Events in Clinical Trials (with a Particular Focus on the Use of Meta Analysis) 109Jesse A. Berlin, Brenda Crowe, and H. Amy Xia10 Case Reports as Evidence in Pharmacovigilance 121Jeffrey K. Aronson11 Periodic Safety Update Reports 139Patrice Verpillat and Mondher Toumi12 The Principles behind Risk Management in the European Union 153Stella C.F. Blackburn and June M. RaineII Pharmacovigilance SystemsPharmacovigilance in Europe13a Regulatory Pharmacovigilance in the European Union 173Priya Bahri and Peter Arlett13b Spontaneous Reporting: United Kingdom 185Mick Foy, Paul Barrow, and June M. Raine13c Spontaneous Reporting: France 203Jacques Caron, Sophie Gautier, and Michel Mallaret13d How Pharmacovigilance is Organized in Germany 207Ulrich Hagemann and Norbert Paeschke13e Organization of Pharmacovigilance in the Netherlands 213Eugène Van Puijenbroek and Kees Van Grootheest13f Pharmacovigilance in Spain 217Dolores Montero, Miguel Angel Maciá, and César De La Fuente13g Italian Pharmacovigilance System 221Laura Sottosanti and Fernanda Ferrazin13h Pharmacovigilance in Turkey 225Sinem Ezgi GülmezPharmacovigilance in the Americas14a Spontaneous Reporting and Pharmacovigilance Practice: USA 229Min-Chu Chen, Solomon Iyasu, Alfred Sorbello, and Linda Scarazzini14b Spontaneous Reporting in Mexico 241Alejandra Rosete and Ricardo Benítez-Vázquez14c Pharmacovigilance in Argentina: A Lot Done, A Lot To Do 245Luis Alesso and Raquel Herrera ComoglioPharmacovigilance in Asia15a Pharmacovigilance and Risk Management in Japan 249Kiyoshi Kubota and Tsugumichi Sato15b Pharmacovigilance in Hong Kong 259Thomas Y.K. Chan15c Pharmacovigilance in China 263Hong-Hao Zhou, Fan-Dian Zeng, and Jie Tang15d China 267Kenneth Hartigan-Go and Althea Bongat15e Malaysia 271Kenneth Hartigan-Go and Althea Bongat15f Philippines 273Kenneth Hartigan-Go and Althea Bongat15g Singapore 277Kenneth Hartigan-Go and Althea Bongat15h Thailand 279Kenneth Hartigan-Go and Althea Bongat15i Vietnam 283Kenneth Hartigan-Go and Althea Bongat15j Pharmacovigilance in India 285Pipasha BiswasPharmacovigilance in New Zealand and Australia16a Pharmacovigilance in New Zealand 291Mira Harrison-Woolrych, Michael Tatley, and Desiree Kunac16b Pharmacovigilance: Australia 295John MCEwenPharmacovigilance in Africa17 Pharmacovigilance in Africa 299Alexander N.O. Dodoo and Haggar H. AmpaduIII Signal Detection/Generation in Spontaneous ReportingPrograms and Other Sources: From Spontaneous Reporting To Pharmacoepidemiology18 Vaccine Safety Surveillance 305Emily Jane Woo, Jerry Labadie, and M. Miles Braun19 How We Assess Causality 319Judith K. Jones and Elyse Kingery20 Quantitative Signal Detection and Analysis in Pharmacovigilance 331Andrew Bate, Antoine Pariente, Manfred Hauben, and Bernard Bégaud21 Self-Controlled Case Series Analysis 355Paddy Farrington22 Prescription–Event Monitoring (PEM): The Evolution to the New Modifi ed PEM and its Support of Risk Management 359Deborah Layton and Saad Shakir23 Prescription–Event Monitoring in New Zealand 385Mira Harrison-Woolrych24 A Description of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance as a Global Resource for Pharmacovigilance and Pharmacoepidemiology 403Thomas Goedecke and Peter Arlett25 Overview of North American Databases 409Brian L. Strom, Rita Schinnar, and Judith L. Kinman26 The Clinical Practice Research Datalink: The New 54 Million Fully Integrated Research Data and Clinical Trial System 421John Parkinson27 Active Surveillance: The United States Food and Drug Administration’s Sentinel Initiative 429Ryan M. Carnahan, Carlos J. Bell, and Richard Platt28 Leveraging Routinely Collected Healthcare Data to Scale Up Drug Safety Surveillance: The EU-ADR Experience 439Gianluca Trifi rò and Preciosa Coloma29 Development and Evaluation of Infrastructure and Analytic Methods for Systematic Drug Safety Surveillance: Lessons and Resources from the Observational Medical Outcomes Partnership 453Paul Stang, Patrick Ryan, Abraham G. Hartzema, David Madigan, J. Marc Overhage, Emily Welebob, Christian G. Reich, and Thomas ScarnecchiaIV Pharmacovigilance and Drug/System Organ Classes30 Mechanisms of Adverse Drug Reactions 465Munir Pirmohamed31 Fatal Medication Errors and Adverse Drug Reactions 489Robin E. Ferner and Sarah E. Mcdowell32 Dermatological Adverse Drug Reactions 503Laurence Valeyrie-Allanore and Jean-Claude Roujeau33 Gastrointestinal Adverse Drug Reactions 513Angel Lanas Arbeloa and Carlos Sostres Homedes34 Hematological Adverse Drug Reactions 527Peter J. Carey35 Hepatic Adverse Drug Reactions 539Guruprasad P. Aithal and Dominique Larrey36 Ocular Side Effects of Prescription Medications 557Frederick W. Fraunfelder37 Renal Adverse Drug Reactions 567Gert A. Verpooten38 The Cardiovascular Spectrum of Adverse Drug Reactions 577Charles Schubert and Judith Hsia39 Neurological Adverse Events 585Bradford B. WaltersSpecial Populations40 Drug Safety in Pregnancy 611Christina D. Chambers and Elizabeth B. Andrews41 Pharmacovigilance in Pediatrics 625M. Dianne Murphy, Judith Cope, and Solomon Iyasu42 Drugs and the Elderly 639Jamie J. ColemanSpecial Product Classes43 Anesthetic Adverse Drug Reactions 659Anita Holdcroft and Karine Nouette-Gaulain44 Pharmacoepidemiology as Part of Pharmacovigilance for Biologic Therapies 685John Acquavella, Brian Bradbury, Cathy Critchlow, Jason B. Litten, J. Michael Sprafka, and John Sullivan45 Surveillance for Medical Devices: USA 703Thomas P. Gross46 The Effi cacy and Safety of Selective Serotonin Reuptake Inhibitors for the Treatment of Depression in Children and Adolescents 719J. Magno Zito, D.J. Safer, and Satish Valluri47 Nonsteroidal Anti-infl ammatory Drugs – Cyclooxygenase-2 Inhibitors: Risks and Benefits 735K. Arnold Chan48 Introduction to Pharmionics: The Vagaries in Ambulatory Patients’ Adherence to Prescribed Drug Dosing Regimens, and Some of Their Clinical and Economic Consequences 751John Urquhart and Bernard Vrijens49 Design and Implementation of Surveys to Assess Patient and Healthcare Provider Understanding of Risks and Safe Use Conditions 769Kelly Hollis and Alicia GilsenanVI Training and Education And Directions50 Eu2P: The First European Online Public–Private Joint Training Program in Pharmacovigilance and Pharmacoepidemiology 787Karine Palin, Christa Bataille, Stéphane Liège, Ralph Schimmer, and Annie Fourrier-Réglat51 Teaching and Learning Pharmacovigilance 793Frank May52 Practical Experience in Teaching Pharmacovigilance 805Stephen Evans and Ian Douglas53 An Historical Perspective of the Future of Pharmacovigilance 807Nicholas MooreIndex 819

“I highly recommend this comprehensive reference for everyone who has any role in developing, delivering, or regulating drugs, or educating prescribers to administer these drugs to patients so that drug therapy can maximize efficacy in treating diseases while minimizing adverse events.”   (Doody’s, 9 January 2015)Highly Commended at the BMA Medical Book Awards 2015