Textbook of Pharmacoepidemiology E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 1221

Veröffentlichungsjahr: 2013

Beschreibung

Textbook of Pharmacoepidemiology, Second Edition, provides an introduction to pharmacoepidemiology and the data sources, methods and applications used in clinical research, the pharmaceutical industry
and regulatory agencies.

Drawing upon the fifth edition of the authoritative reference, Pharmacoepidemiology, this new edition covers the key learning requirements of the discipline. The textbook provides an introduction to
pharmacoepidemiology, pharmacoepidemiological data sources, special issues in methodology, special applications and future developments in the field. Updated learning features such as case studies, key points and Suggested Further Reading are included throughout the text.

Textbook of Pharmacoepidemiology is a practical educational resource for upper-level undergraduates, graduate students, post-doctoral fellows in schools of public health, pharmacy and medicine, and for everyone learning and working in pharmacoepidemiology.

Leseprobe

Contents

Cover

Title Page

Copyright

Contributors

Preface

Acknowledgements

Part I: Introduction to Pharmacoepidemiology

Chapter 1: What is Pharmacoepidemiology?

Introduction

Definition of Pharmacoepidemiology

Historical Background

The Current Drug Approval Process

Potential Contributions of Pharmacoepidemiology

Key Points

Further Reading

Chapter 2: Study Designs Available for Pharmacoepidemiologic Studies

Overview of the Scientific Method

Types of Errors that One can Make in Performing a Study

Criteria for the Causal Nature of an Association

Epidemiologic Study Designs

Case Reports

Conclusion

Key Points

Further Reading

Chapter 3: Sample Size Considerations for Pharmacoepidemiologic Studies

Introduction

Sample Size Calculations for Cohort Studies

Sample Size Calculations for Case-Control Studies

Sample Size Calculations for Case Series

Discussion

Key Points

References and Further Readings

Chapter 4: Basic Principles of Clinical Pharmacology Relevant to Pharmacoepidemiologic Studies

Clinical Pharmacology and Pharmacoepidemiology

Basics of Clinical Pharmacology

Pharmacokinetics

Special Populations

Pharmacodynamics

Pharmacogenomics

Conclusion

Key Points

Further Reading

Chapter 5: When Should One Perform Pharmacoepidemiologic Studies?

Reasons to Perform Pharmacoepidemiologic Studies

Safety versus Risk

Risk Tolerance

Conclusion

Key Points

Further Reading

Chapter 6: Views from Academia, Industry, Regulatory Agencies, and the Legal System

The View from Academia

Summary Points for the View from Academia

The View from Industry

The View from Regulatory Agencies

The View from the Legal System

Further Reading

Part II: Sources of Pharmacoepidemiology Data

Chapter 7: Postmarketing Spontaneous Pharmacovigilance Reporting Systems

Introduction

Description

Strengths

Limitations

Particular Applications

The Future

Key Points

Further Reading

Chapter 8: Overview of Automated Databases in Pharmacoepidemiology

Introduction

Description

Strengths

Weaknesses

Particular Applications

The Future

Key Points

Further Reading

Chapter 9: Examples of Existing Automated Databases

US Health Maintenance Organizations/Health Plans

US Government Claims Databases

Canadian Provincial Databases

Medical Record Databases

Pharmacy-Based Medical Record Linkage Systems

Further Reading

Chapter 10: Field Studies

Strengths

Weaknesses

Particular Applications

Conclusions

Key Points

Further Reading

Chapter 11: How Should One Perform Pharmacoepidemiologic Studies? Choosing Among the Available Alternatives

Introduction

Choosing Among the Available Approaches to Pharmacoepidemiologic Studies

Examples

Conclusion

Key Points

Further Reading

Part III: Special Issues in Pharmacoepidemiology Methodology

Chapter 12: Validity of Pharmacoepidemiologic Drug and Diagnosis Data

Introduction

Clinical Problems to be Addressed by Pharmacoepidemiologic Research

Methodological Problems to be Solved by Pharmacoepidemiologic Research

Methodological Problems in Pharmacoepidemiologic Research

Currently Available Solutions

The Future

Key Points

Further Reading

Chapter 13: Assessing Causality of Case Reports of Suspected Adverse Events

Introduction

Clinical Problems to be Addressed by Pharmacoepidemiologic Research

Historical Perspectives: Development of Concepts

Uses of Causality Assessment

Methodological Problems to be Addressed by Pharmacoepidemiologic Research

Current Tools

Unstructured Clinical Judgment/Global Introspection

Algorithm/Criterial Method with Verbal Judgments

Algorithms Requiring Scoring of Individual Judgments

Probabilistic Methods

Comparison Among the Different Methods

The Future

Key Points

Further Reading

Chapter 14: Molecular Pharmacoepidemiology

Introduction

Definitions and Concepts

The Interface of Pharmacogenetics and Pharmacogenomics with Molecular Pharmacoepidemiology

Clinical Problems to be Addressed by Pharmacoepidemiologic Research

Three Ways that Genes can Affect Drug Response

The Progression and Application of Molecular Pharmacoepidemiologic Research

Methodological Problems to be Addressed by Pharmacoepidemiologic Research

Currently Available Solutions

The Future

Key Points

Further Reading

Chapter 15: Bioethical Issues in Pharmacoepidemiologic Research

Introduction

Clinical Problems to be Addressed by Pharmacoepidemiologic Research

Methodological Problems to be Addressed by Pharmacoepidemiologic Research

Currently Available Solutions

Conclusion

Key Points

Further Reading

Chapter 16: The Use of Randomized Controlled Trials for Pharmacoepidemiologic Studies

Introduction

Clinical Problems to be Addressed by Pharmacoepidemiologic Research

Methodological Problems to be Solved by Pharmacoepidemiologic Research

Currently Available Solutions

The Future

Key Points

Further Reading

Chapter 17: Pharmacoeconomics: Economic Evaluation of Pharmaceuticals

Clinical Problems to be Addressed by Pharmacoeconomic Research

Economic Evaluation and the Drug Development Process

Methodological Problems to be Addressed by Pharmacoeconomic Research

Methodological Issues in the Pharmacoeconomic Assessment of Therapies

The Future

Key Points

Further Reading

Chapter 18: Using Quality-of-Life Measurements in Pharmacoepidemiologic Research

Introduction

Clinical Problems to be Addressed by Pharmacoepidemiologic Research

Methodological Problems to be Addressed by Pharmacoepidemiologic Research

Currently Available Solutions

The Future

Key Points

Further Reading

Chapter 19: The Use of Meta-analysis in Pharmacoepidemiology

Introduction

Clinical Problems to be Addressed by Pharmacoepidemiologic Research

Methodological Problems to be Addressed by Pharmacoepidemiologic Research

Currently Available Solutions

Currently Available Solutions

The Future

Key Points

Further Reading

Chapter 20: Studies of Medication Adherence

Introduction

Clinical Problems to be Addressed by Pharmacoepidemiologic Research

Methodologic Problems to be Solved by Pharmacoepidemiologic Research

Currently Available Solutions

Future Directions

Key Points

Further Reading

Chapter 21: Advanced Approaches to Controlling Confounding in Pharmacoepidemiologic Studies

Clinical Problems to be Addressed by Pharmacoepidemiologic Research

Methodological Problems to be Addressed by Pharmacoepidemiologic Research

Currently Available Solutions

Conclusion

Key Points

Further Reading

Part IV: Special Applications

Chapter 22: Special Applications of Pharmacoepidemiology

Studies of Drug Utilization

Evaluating and Improving Physician Prescribing

Special Methodological Issues in Pharmacoepidemiologic Studies of Vaccine Safety

Key Points for Special Methodological Issues in Pharmacoepidemiologic Studies of Vaccine Study

Epidemiologic Studies of Implantable Medical Devices

Studies of Drug-Induced Birth Defects

Risk Management

The Use of Pharmacoepidemiology to Study Medication Errors

FDA's Sentinel Initiative: Enhancing Safety Surveillance

Comparative Effectiveness Research

Further Reading

Chapter 23: The Future of Pharmacoepidemiology

The View from Academia

The View from Industry

The View from Regulatory Agencies

The View from the Law

Conclusion

Key Points

Further Reading

Appendix A: Sample Size Tables

Appendix B: Glossary

Index

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Library of Congress Cataloging-in-Publication Data

Textbook of pharmacoepidemiology / edited by Brian L. Strom, Stephen E. Kimmel, Sean Hennessy. – 2nd ed.

p. ; cm.

Abridged version of: Pharmacoepidemiology. 5th ed. 2012.

Includes bibliographical references and index.

ISBN 978-1-118-34486-6 (pbk. : alk. paper)

I. Strom, Brian L. II. Kimmel, Stephen E. III. Hennessy, Sean. IV. Pharmacoepidemiology.

[DNLM: 1. Pharmacoepidemiology–methods. QZ 42]

RM302.5

615.7'042–dc23

2013002833

A catalogue record for this book is available from the British Library.

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.

Cover image: iStock © FotografiaBasica, Karina Tischlinger

Cover design by Rob Sawkins for Opta Design

Contributors

Trisha Acri

Formerly, Assistant Professor

of Family and Community Medicine

Temple University School of Medicine

Philadelphia, PA Currently, Director of Community Research Health Services

AIDS Care Group

Sharon Hill, PA

USA

Susan E. Andrade

Senior Research Associate and

Research Associate Professor

Meyers Primary Care Institute

and

University of Massachusetts Medical School

Worcester, MA

USA

Peter Arlett

Head

Pharmacovigilance and Risk

Management

European Medicines Agency

London, UK

Jerry Avorn

Professor of Medicine

Harvard Medical School

and

Chief

Division of Pharmacoepidemiology and Pharmacoeconomics

Brigham and Women's Hospital

Boston, MA

USA

Jeffrey S. Barrett

Director

Laboratory for Applied Pharmacokinetics and Pharmacodynamics

Director

Pediatric Pharmacology Research Unit

The Children's Hospital of Philadelphia

Research Professor of Pediatrics

Kinetic Modeling and Simulation (KMAS) Core Director

Perelman School of Medicine at the University of Pennsylvania

Colket Translational Research

Philadelphia, PA

USA

David W. Bates

Division of General Internal Medicine and Primary Care

Brigham and Women's Hospital

and

Harvard Medical School

Boston, Massachusetts

USA

Jesse A. Berlin

Vice President

Epidemiology

Janssen Research & Development, LLC

Johnson & Johnson

Titusville, NJ

USA

Stella Blackburn

EMA Risk Management Development

and Scientific Lead

European Medicines Agency

London, UK

Denise M. Boudreau

Scientific Investigator

Group Health Research Institute

Seattle, WA

USA

M. Soledad Cepeda

Director

Epidemiology

Janssen Research & Development, LLC

Johnson & Johnson

Titusville, NJ

USA

Robert T. Chen

Medical Officer

Clinical Trials Team

Epidemiology Branch

Division of HIV/AIDS Prevention

Centers for Disease Control and Prevention

Atlanta, GA

USA

Francesca Cunningham

Director

Center for Medication Safety

and

Program Manager

Outcomes Research PBM Services

Department of Veterans Affairs

Center for Medication Safety

Hines, IL

USA

Gerald J. Dal Pan

Director

Office of Surveillance and Epidemiology

Center for Drug Evaluation and Research

US Food and Drug Administration

Silver Spring, MD

USA

Hassy Dattani

Research Director (retired)

Cegedim Strategic Data Medical

Research Ltd

London, UK

Robert L. Davis

Director of Research

Center for Health Research

Southeast Kaiser Permanente

Atlanta, GA

USA

Antoine C. El Khoury

Director

Market Access and Health Economics

Johnson & Johnson Pharmaceutical

Horsham, PA

USA

Joel M. Gelfand

Associate Professor of Dermatology and Epidemiology

Center for Clinical

Epidemiology and Biostatistics

Center for Pharmacoepidemiology Research and Training

Perelman School of Medicine at the University of Pennsylvania

Philadelphia, PA

USA

Kate Gelperin

Medical Officer

Division of Epidemiology

Office of Surveillance and Epidemiology

Center for Drug Evaluation and Research

US Food and Drug Administration

Silver Spring, MD

USA

Jason Glanz

Epidemiologist

Institute for Health Research

Kaiser Permanente Colorado

Department of Epidemiology Colorado

School of Public Health

Denver, CO

USA

Henry A. Glick

Professor of Medicine

Perelman School of Medicine at the University of Pennsylvania

Philadelphia, PA

USA

Robert Gross

Associate Professor of Medicine and Epidemiology

Center for Clinical Epidemiology and Biostatistics

Center for Pharmacoepidemiology Research and Training

Perelman School of Medicine at the University of Pennsylvania

Philadelphia, PA

USA

Gordon H. Guyatt

Professor

Department of Clinical Epidemiology and Biostatistics

McMaster University

Health Sciences Center

and

Department of Medicine

St Joseph's Hospital

Hamilton, Ontario

Canada

Katherine Haffenreffer

Project Administrator

Harvard Pilgrim Health Care Institute

and

Department of Population Medicine

Harvard Medical School

Boston, MA

USA

Sean Hennessy

Associate Professor of Epidemiology

and of Pharmacology

Center for Clinical Epidemiology and Biostatistics

Director,

Center for Pharmacoepidemiology

Research and Training

Perelman School of Medicine at the University of Pennsylvania

Philadelphia, PA

USA

Ron M.C. Herings

Director

PHARMO Institute

Utrecht, The Netherlands

and

Associate Professor of

Pharmaceutical Technology Assessment

Erasmus University Rotterdam

Rotterdam, The Netherlands

Roman Jaeschke

Professor of Clinical Epidemiology and Biostatistics

McMaster University

Health Sciences Center

and

Professor of Medicine

St Joseph's Hospital

Hamilton, Ontario

Canada

Bradley C. Johnston

Assistant Professor of Clinical Epidemiology and Biostatistics McMaster University

Hamilton, Ontario

and

Assistant Professor

Institute of Health Policy Management and Evaluation and Department of Anesthesia & Pain Medicine, University of Toronto

and

Scientist

The Hospital for Sick Children Research Institute

Toronto, Ontario

Canada

Judith K. Jones

President and CEO

The Degge Group Ltd

Arlington, VA

and

Adjunct Professor

Georgetown University

Washington, DC

USA

Jason Karlawish

Professor of Medicine

Perelman School of Medicine at the University of Pennsylvania

Philadelphia, PA

USA

David W. Kaufman

Associate Director

Slone Epidemiology Center at Boston University

and

Professor of Epidemiology

Boston University School of Public Health

Boston, MA

USA

Aaron S. Kesselheim

Assistant Professor of Medicine

Division of Pharmacoepidemiology and Pharmacoeconomics

Brigham and Women's Hospital

Harvard Medical School

Boston, MA

USA

Stephen E. Kimmel

Professor of Medicine and Epidemiology

Center for Clinical

Epidemiology and Biostatistics

Center for Pharmacoepidemiology

Research and Training

Perelman School of Medicine at the University of Pennsylvania

Philadelphia, PA

USA

Karel Kostev

Senior Research Analyst

Centre of Excellence Patient Data

IMS Health GmbH & Co OHG

Frankfurt/Main, Germany

Sinéad M. Langan

NIHR Clinician Scientist

London School of Hygiene and Tropical Medicine

and

Honorary Consultant Dermatologist

St John's Institute of Dermatology

London, UK

David Lee

Director

Technical Strategy and Quality

Center for Pharmaceutical

Management

Management Sciences for Health, Inc.

Arlington, VA

USA

Samuel M. Lesko

Medical Director

Northeast Regional Cancer Institute

Scranton, PA

and

Adjunct Professor of Basic Sciences

The Commonwealth Medical College

Scranton, PA

and

Adjunct Professor of Public Health Sciences

Pennsylvania State University College of Medicine

Hershey, PA

USA

Hubert G. Leufkens

Professor of Pharmacoepidemiology and Clinical Pharmacotherapy

Utrecht Institute for Pharmaceutical Sciences

Utrecht University

Utrecht, The Netherlands

Marie Lindquist

Director

Uppsala Monitoring Centre

WHO Collaborating Centre for International Drug Monitoring

Uppsala, Sweden

Helene Levens Lipton

Professor of Pharmacy and Health Policy

Schools of Medicine and Pharmacy

University of California at San

Francisco

San Francisco, CA

USA

Sumit R. Majumdar

Professor of Medicine

Faculty of Medicine and Dentistry

University of Alberta

Edmonton, Alberta

Canada

Claudia Manzo

Director

Division of Risk Management

Office of Surveillance and Epidemiology

Center for Drug Evaluation and Research

US Food and Drug Administration

Silver Spring, MD

USA

Danica Marinac-Dabic

Director

Division of Epidemiology

Office of Surveillance and Biometrics

Center for Devices and Radiological Health

US Food and Drug Administration

Silver Spring, MD

USA

Allen A. Mitchell

Director

Slone Epidemiology Center at Boston University

and

Professor of Epidemiology and Pediatrics

Boston University Schools of Public

Health and Medicine

Boston, MA

USA

Jingping Mo

Senior Director

Epidemiology

Worldwide Research & Development

Pfizer Inc.

New York, NY

USA

Yola Moride

Full Professor

Faculty of Pharmacy

Université de Montréal

and

Researcher

CHUM Research Center (CRCHUM)

Montreal, Quebec Canada

Sharon-Lise T. Normand

Professor of Health Care Policy

(Biostatistics)

Harvard Medical School

and

Professor of Biostatistics

Harvard School of Public Health

Boston, MA

USA

Alexis Ogdie

Instructor in Medicine

Division of Rheumatology

Center for Clinical Epidemiology and Biostatistics

Center for Pharmacoepidemiology

Research and Training

Perelman School of Medicine at the University of Pennsylvania

Philadelphia, PA

USA

Cristin Palumbo Freeman

Research Project Manager

Center for Clinical Epidemiology and Biostatistics

Center for Pharmacoepidemiology

Research and Training

Perelman School of Medicine at the University of Pennsylvania

Philadelphia, PA

USA

John Parkinson

Director

Clinical Practice Research Datalink (CPRD)

Medicines and Healthcare Products

Regulatory Agency (MHRA)

London, UK

Pamala A. Pawloski

HealthPartners Institute for Education and Research

Bloomington, MN

and

Adjunct Assistant Professor

University of Minnesota College of Pharmacy

Minneapolis, MN

USA

Lars Pedersen

Professor of Clinical

Epidemiology

Department of Clinical Epidemiology

Aarhus University Hospital

Aarhus, Denmark

Richard Platt

Professor and Chair

Department of Population Medicine, Harvard Medical School

and

Executive Director

Harvard Pilgrim Health Care Institute

Boston, MA

USA

Daniel Polsky

Executive Director, Leonard Davis

Institute for Health Economics Professor of Medicine

Perelman School of Medicine at the University of Pennsylvania

Philadelphia, PA

USA

Charles Poole

Associate Professor of Epidemiology

Gillings School of Global Public Health

University of North Carolina

Chapel Hill, NC

USA

Marsha A. Raebel

Investigator

Institute for Health Research

Kaiser Permanente Colorado

and

Clinical Professor

University of Colorado

Skaggs School of Pharmacy and Pharmaceutical Sciences

Aurora, CO

USA

Timothy R. Rebbeck

Professor of Epidemiology

Center for Clinical

Epidemiology and Biostatistics

Perelman School of Medicine at the University of Pennsylvania

Philadelphia, PA

USA

Shelby D. Reed

Associate Professor of Medicine

Duke University School of Medicine

Durham, NC

USA

Robert F. Reynolds

Vice President

Epidemiology Worldwide Research & Development

Pfizer Inc.

New York, NY

USA

Mary Elizabeth Ritchey

Associate Division Director

Food and Drug Administration

Center for Devices and Radiological

Health

Silver Spring, MD

USA

Melissa A. Robb

Associate Director for Regulatory Affairs

Office of Medical Policy Initiatives

Center for Drug Evaluation and Research

US Food and Drug Administration

Silver Spring, MD

USA

Rita Schinnar

Senior Research Project Manager and Analyst

Center for Clinical Epidemiology and Biostatistics

Center for Pharmacoepidemiology Research and Training

Perelman School of Medicine at the University of Pennsylvania

Philadelphia, PA

USA

Sebastian Schneeweiss

Professor of Medicine and

Epidemiology

Harvard Medical School

and

Vice Chief

Division of Pharmacoepidemiology

Department of Medicine

Brigham & Women's Hospital

Boston, MA

USA

Kevin A. Schulman

Professor of Medicine and Gregory

Mario and Jeremy Mario Professor of Business Administration

Duke University

Durham, NC

USA

Holger J. Schünemann

Professor and Chair

Department of Clinical Epidemiology and Biostatistics

Health Sciences Center

and

Professor of Medicine

McMaster University

Hamilton, Ontario

Canada

Art Sedrakyan

Associate Professor of Public Health

New York Presbyterian Hospital

and

Weill Cornell Medical College

New York, NY

USA

Hanna M. Seidling

Head of Cooperation Unit Clinical Pharmacy

Department of Clinical Pharmacology and Pharmacoepidemiology

Cooperation Unit Clinical Pharmacy

University of Heidelberg

Heidelberg, Germany

Rachel E. Sherman

Associate Director for Medical Policy

Center for Drug Evaluation and Research

US Food and Drug Administration

Silver Spring, MD

USA

Stephen B. Soumerai

Professor of Population Medicine

Director

Drug Policy Research Group

Harvard Medical School and Harvard

Pilgrim Health Care Institute

Boston, MA

USA

Brian L. Strom

Executive Vice Dean for Institutional Affairs

George S. Pepper Professor of Public Health and Preventive Medicine

Professor of Biostatistics and Epidemiology, of Medicine, and of Pharmacology

Center for Clinical Epidemiology and Biostatistics

Center for Pharmacoepidemiology Research and Training

Perelman School of Medicine at the University of Pennsylvania

Philadelphia, PA

USA

Samy Suissa

James McGill Professor of Epidemiology, Biostatistics and Medicine

McGill University

and

Director

Centre for Clinical Epidemiology

Lady Davis Research Institute

Jewish General Hospital

Montreal, Quebec

Canada

Sengwee Toh

Assistant Professor of Population Medicine

Harvard Medical School and Harvard

Pilgrim Health Care Institute

Boston, MA

USA

Claudia Vellozzi

Deputy Director

Immunization Safety Office

Division of Healthcare Quality

Promotion

Centers for Disease Control and Prevention

Atlanta, GA

USA

Suzanne L. West

RTI Fellow and Senior Scientist

RTI International

Research Triangle Park, NC

and

Department of Epidemiology

Gillings School of Global Public Health

University of North Carolina

Chapel Hill, NC

USA

Athena F. Zuppa

Associate Professor of Pediatrics, Anesthesia and Critical Care Medicine

Laboratory for Applied

Pharmacokinetics and Pharmacodynamics

Children's Hospital of Philadelphia

Perelman School of Medicine at the University of Pennsylvania

Philadelphia, PA

USA

Preface

It was a remarkable 23 years ago that the first edition of Strom's Pharmacoepidemiology was published. The preface to that book stated that pharmacoepidemiology was a new field with a new generation of pharmacoepidemiologists arising to join the field's few pioneers. Over the ensuing 23 years, the field indeed has grown and no longer deserves to be called “new.” Many of those “new generation” scientists (including two of the editors of this book) are now “middle-aged” pharmacoepidemiologists. Despite its relatively brief academic life, a short history of pharmacoepidemiology and review of its current state will set the stage for the purpose of this textbook.

Pharmacoepidemiology originally arose from the union of the fields of clinical pharmacology and epidemiology. Pharmacoepidemiology studies the use of and the effects of medical products in large numbers of people and applies the methods of epidemiology to the content area of clinical pharmacology. This field represents the science underlying postmarketing medical product surveillance, studies of the effects of medical products (i.e., drugs, biologicals, devices) performed after a product has been approved for use. In recent years, pharmacoepidemiology has expanded to include many other types of studies, as well.

The field of pharmacoepidemiology has grown enormously since the first publication of Strom. The International Society of Pharmacoepidemiology, an early idea when the first edition of this book was written, has grown into a major international scientific force, with over 1460 members from 54 countries, an extremely successful annual meeting attracting more than 1200 attendees, a large number of very active committees and scientific interest groups, and its own journal. In addition, a number of established journals have targeted pharmacoepidemiology manuscripts as desirable. As new scientific developments occur within mainstream epidemiology, they are rapidly adopted, applied, and advanced within our field as well. We have also become institutionalized as a subfield within the field of clinical pharmacology, with the Drug Safety Scientific Section of the American Society for Clinical Pharmacology and Therapeutics, and with pharmacoepidemiology a required part of the clinical pharmacology board examination.

Most of the major international pharmaceutical companies have founded dedicated units to organize and lead their efforts in pharmacoepidemiology, pharmacoeconomics, and quality-of-life studies. The continuing parade of drug safety crises emphasizes the need for the field, and some foresighted manufacturers have begun to perform “prophylactic” pharmacoepidemiology studies, to have data in hand and available when questions arise, rather than waiting to begin to collect data after a crisis has developed. Pharmacoepidemiologic data are now routinely used for regulatory decisions, and many governmental agencies have been developing and expanding their own pharmacoepidemiology programs. Risk evaluation and mitigation strategies are now required by regulatory bodies with the marketing of new drugs, as a means of improving drugs' benefit/risk balance, and manufacturers are identifying ways to respond. Requirements that a drug be proven to be cost-effective have been added to many national, local, and insurance health care systems, either to justify reimbursement or even to justify drug availability. A number of schools of medicine, pharmacy, and public health have established research programs in pharmacoepidemiology, and a few of them have also established pharmacoepidemiology training programs in response to a desperate need for more pharmacoepidemiology personnel. Pharmacoepidemiologic research funding is now more plentiful, and even limited support for training is available.

In the United States, drug utilization review programs are required, by law, of each of the 50 state Medicaid programs, and have been implemented as well in many managed care organizations. Now, years later, the utility of drug utilization review programs is being questioned. In addition, the Joint Commission on Accreditation of Health Care Organizations now requires that every hospital in the country have an adverse drug reaction monitoring program and a drug use evaluation program, turning every hospital into a mini-pharmacoepidemiology laboratory. Stimulated in part by the interests of the World Health Organization and the Rockefeller Foundation, there is even substantial interest in pharmacoepidemiology in the developing world. Yet, throughout the world, the increased concern by the public about privacy has made pharmacoepidemiologic research much more difficult to conduct.

In recent years, major new changes have been made in drug regulation and organization, largely in response to a series of accusations about myocardial infarction caused by analgesics, which was detected in long-term prevention trials rather than in normal use of the drugs. For example, FDA has been given new regulatory authority after drug marketing, and has also begun developing the Sentinel Initiative, a program to conduct medical product safety surveillance in a population to exceed 100 million. Further, the development, since January 1, 2006, of Medicare Part D, a US federal program to subsidize prescription drugs for Medicare recipients, introduces to pharmacoepidemiology a new database with a stable population of about 25 million in what may be the largest healthcare system in the world. A new movement has arisen in the US of “comparative effectiveness research,” which in many ways learns from much longer experience in Europe, as well as decades of experience in pharmacoepidemiology. These developments portend major changes for our field.

In summary, there has been tremendous growth in the field of pharmacoepidemiology and a fair amount of maturation. With the growth and maturation of the field, Strom's Pharmacoepidemiology has grown and matured right along. Pharmacoepidemiology thus represents a comprehensive source of information about the field. As a reflection of the growth of the field, the 4th Edition of Strom was over twice as long as the first! We worked hard to avoid such growth in the 5th Edition, by aggressive pruning to go along with our additions.

So, why, one may ask, do we need a Textbook of Pharmacoepidemiology? The need arose precisely because of the growth of the field. With that, and the corresponding growth in the parent book, Strom's Pharmacoepidemiology has really become more of a reference book than a book usable as a textbook. Yet, there is increasing need for people to be trained in the field, and an increasing number of training programs. With the maturity of the field comes therefore the necessity for both comprehensive approaches (such as Strom's Pharmacoepidemiology) and more focused approaches. Therefore, Textbook of Pharmacoepidemiology was intended as a modified and shortened version of its parent, designed to meet the need of students. We believe that students can benefit from an approach that focuses on the core of the discipline, along with learning aids.

Textbook of Pharmacoepidemiology attempts to fill this need, providing a focused educational resource for students. It is our hope that this book will serve as a useful textbook for students at all levels: upper-level undergraduates, graduate students, post-doctoral fellows, and others who are learning the field. In order to achieve our goals, we have substantially shortened Strom's Pharmacoepidemiology, with a focus on what is needed by students, eliminating some chapters and shortening others. We also have provided case examples for most chapters and key points for all chapters. Each chapter is followed by a list of further reading.

So why update it? In looking at the 5th Edition of Strom, most chapters in the new edition were thoroughly revised. Ten new chapters were added, along with many new authors. The first edition of the textbook was simply getting out of date.

Specifically, we have tried to emphasize the methods of pharmacoepidemiology and the strengths and limitations of the field, while minimizing some of the technical specifications that are important for a reference book but not for students. Therefore, the first five chapters of Part I, “Introduction to Pharmacoepidemiology,” lay out the cores of the discipline, and remain essentially unchanged from Strom's Pharmacoepidemiology, with the exception of the inclusion of key points and lists of further reading. We have also included a chapter on different perspectives of the field (from academia, industry, regulatory agencies, and the legal system), as a shortened form of several chapters from the reference book. Part II focuses on “Sources of Pharmacoepidemiology Data” and includes important chapters about spontaneous pharmacovigilance reporting systems, and other approaches to pharmacoepidemiology studies. A substantially shortened chapter on Examples of Automated Databases is included, focused on the strengths and limitations of these data sources rather than providing extensive details about the content of each database. Part III summarizes “Special Issues in Pharmacoepidemiology Methodology” that we feel are important to more advanced pharmacoepidemiology students. Although no student is likely to become an expert in all of these methods, they form a core set of knowledge that we believe all pharmacoepidemiologists should have. In addition, one never knows what one will do later in one's own career, nor when one may be called upon to help others with the use of these methods. Part IV concludes the textbook with a collection of “Special Applications” of the field, and speculation about its future, always an important consideration for new investigators in charting a career path.

Pharmacoepidemiology may be maturing, but many exciting opportunities and challenges lie ahead as the field continues to grow and respond to unforeseeable future events. It is our hope that this book can serve as a useful introduction and resource for students of pharmacoepidemiology, both those enrolled in formal classes and those learning in “the real world,” who will respond to the challenges that they encounter. Of course, we are always students of our own discipline, and the process of developing this textbook has been educational for us. We hope that this book will also be stimulating and educational for you.

Brian L. Strom, M.D., M.P.H.

Stephen E. Kimmel, M.D., M.S.C.E.

Sean Hennessy, Pharm.D., Ph.D.

Acknowledgements

There are many individuals and institutions to whom we owe thanks for their contributions to our efforts in preparing this book. Over the years, our pharmacoepidemiology work has been supported mostly by numerous grants from government, foundations, and industry. While none of this support was specifically intended to support the development of this book, without this assistance, we would not have been able to support our careers in pharmacoepidemiology. We would like to thank our publisher, John Wiley & Sons, Ltd., for their assistance and insights, both in support of this book, and in support of the field's journal, Pharmacoepidemiology and Drug Safety.

Rita Schinnar's contributions to this book were instrumental in helping to shorten several of the chapters that were merged together from Pharmacoepidemiology, 5th edition, and providing excellent editorial assistance with all the other chapters, as well as contributing a chapter. She also coordinated the entire process of contacting the authors and pulling the book together. Finally, we would like to thank all of the authors for the work that they did in helping to revise their book chapters for this textbook and provide case examples, key points, and suggested readings.

BLS would like to thank Steve Kimmel and Sean Hennessy for joining him as co-editors in this edition. Steve did the bulk of the work on the first edition of this textbook, and Steve and Sean joined BLS as co-editors for the 5th edition of Pharmacoepidemiology. These are two very special and talented men. It has been BLS's pleasure to help to train them, now too many years ago, help them cultivate their own careers, and see them blossom into star senior pharmacoepidemiologists in their own right, now extremely effective and successful. It is wonderful to be able to share with them this book, which has been an important part of BLS's life and career.

BLS would also like to thank his parents for the support and education that were critical to his being able to be successful in his career. BLS would also like to thank Paul D. Stolley, M.D., M.P.H. and the late Kenneth L. Melmon, M.D., for their direction, guidance, and inspiration in the formative years of his career. He would also like to thank his trainees, from whom he learns at least as much as he teaches. Last, but certainly not least, BLS would like to thank his family—Lani, Shayna, and Jordi—for accepting the time demands of the book, for tolerating his endless hours working at home (on its earlier editions, for the kids), and for their ever present love and support.

SEK expresses his sincere gratitude to BLS for his 20 years as a mentor and colleague and for the chance to work on this book, to his parents for providing the foundation for all of his work, and to his family—Alison, David, Benjamin, and Jonathan—for all their support and patience.

SH also thanks BLS, his longtime friend and career mentor, and all of his students, mentees, and collaborators. Finally, he thanks his parents, Michael and Catherine; and his family—Kristin, Landis, and Bridget—for their love and support.

Part I

Introduction to Pharmacoepidemiology

Chapter 1

What is Pharmacoepidemiology?

Brian L. Strom

Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

“A desire to take medicine is, perhaps, the great feature which distinguishes man from other animals.”

Sir William Osler, 1891

Introduction

In recent decades, modern medicine has been blessed with a pharmaceutical armamentarium that is much more powerful than what it had before. Although this has given health care providers the ability to provide better medical care for their patients, it has also resulted in the ability to do much greater harm. It has also generated an enormous number of product liability suits against pharmaceutical manufacturers, some appropriate and others inappropriate. In fact, the history of drug regulation parallels the history of major adverse drug reaction “disasters.” Each change in pharmaceutical law was a political reaction to an epidemic of adverse drug reactions. A 1998 study estimated that 100 000 Americans die each year from adverse drug reactions (ADRs), and 1.5 million US hospitalizations each year result from ADRs; yet, 20–70% of ADRs may be preventable. The harm that drugs can cause has also led to the development of the field of pharmacoepidemiology, which is the focus of this book. More recently, the field has expanded its focus to include many issues other than adverse reactions, as well.