About the Editors

Brian L. Strom is Chancellor, Rutgers Biomedical and Health Sciences, University Professor, and Executive Vice President for Health Affairs, Rutgers University, Newark, NJ, USA.

Stephen E. Kimmel is Dean's Professor and Chair of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA.

Sean Hennessy is Professor of Epidemiology and Director of the Center for Pharmacoepidemiology Research and Training, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Contributors xvii Preface xxi Acknowledgements xxv Part I Introduction to Pharmacoepidemiology 1 1 What is Pharmacoepidemiology? 3
Brian L. Strom Introduction 3 Definition of Pharmacoepidemiology 3 Historical Background 5 The Current Drug Approval Process 13 Potential Contributions of Pharmacoepidemiology 15 Key Points 18 Further Reading 18 2 Study Designs Available for Pharmacoepidemiologic Studies 20
Brian L. Strom Introduction 20 Overview of the Scientific Method 20 Types of Errors that one Can Make in Performing a Study 22 Criteria for the Causal Nature of an Association 23 Epidemiologic Study Designs 26 Discussion 31 Conclusion 32 Key Points 32 Further Reading 33 3 Sample Size Considerations for Pharmacoepidemiologic Studies 35
Brian L. Strom Introduction 35 Sample Size Calculations for Cohort Studies 35 Sample Size Calculations for Case-Control Studies 40 Sample Size Calculations for Case Series 41 Discussion 43 Key Points 45 Further Reading 45 4 Basic Principles of Clinical Pharmacology Relevant to Pharmacoepidemiologic Studies 47
Jeffrey S. Barrett Introduction 47 Clinical Pharmacology and Pharmacoepidemiology 48 Basics of Clinical Pharmacology 48 Pharmacokinetics 49 Special Populations 52 Pharmacodynamics 56 Pharmacogenomics 59 Model-Informed Drug Development 59 Conclusion 60 Key Points 60 Further Reading 61 5 When Should One Perform Pharmacoepidemiologic Studies? 62
Brian L. Strom Introduction 62 Reasons to Perform Pharmacoepidemiologic Studies 62 Safety Versus Risk 67 Risk Tolerance 67 Conclusion 70 Key Points 70 Further Reading 71 6 Views from Academia, Industry, Regulatory Agencies, and the Legal System 73
Joshua J. Gagne, Jerry Avorn, Nicolle M. Gatto, Jingping Mo, Gerald J. Dal Pan, June Raine, Shinobu Uzu, Aaron S. Kesselheim, and Kerstin N. Vokinger The View from Academia 73 The View from Industry 81 The View from Regulatory Agencies 90 The View from the Legal System 98 Further Reading 107 Part II Sources of Pharmacoepidemiology Data 113 7 Postmarketing Spontaneous Pharmacovigilance Reporting Systems 115Gerald J. Dal Pan, Marie Lindquist, and Kate Gelperin Introduction 115 Description 116 Strengths 128 Limitations 129 Particular Applications 131 The Future 132 Key Points 132 Further Reading 134 8 Overview of Electronic Databases in Pharmacoepidemiology 136
Brian L. Strom Introduction 136 Description 137 Strengths 138 Weaknesses 139 Particular Applications 140 The Future 140 Key Points 141 Further Reading 141 9 Encounter Databases 142
Tobias Gerhard, Yola Moride, Anton Pottegård, and Nicole Pratt Introduction 142 Description 142 Strengths 161 Limitations 162 Particular Applications 163 The Future 166 Key Points 167 Further Reading 171 US Databases 172 European Databases 172 Canadian Databases 173 Asian Databases 173 10 Electronic Health Record Databases 174
Daniel B. Horton, Harshvinder Bhullar, Francesca Cunningham, Janet Sultana, and Gialuca Trifirò Introduction 174 Description 174 Strengths 184 Limitations 185 The Future 186 Summary Points for Electronic Health Record Databases 187 Acknowledgment 187 Further Readings 189 11 Primary Data Collection for Pharmacoepidemiology 192
Priscilla Velentgas Introduction 192 Methods of Primary Data Collection 195 Strengths 197 Limitations 197 Particular Applications 198 Conclusions 199 Key Points 199 Further Reading 201 12 How Should One Perform Pharmacoepidemiologic Studies? Choosing Among the Available Alternatives 203Brian L. Strom Introduction 203 Choosing Among the Available Approaches to Pharmacoepidemiologic Studies 203 Examples 215 Conclusion 216 Key Points 216 Further Reading 216 Part III Special Issues in Pharmacoepidemiology Methodology 219 13 Validity of Drug and Diagnosis Data in Pharmacoepidemiology 221Mary Elizabeth Ritchey, Suzanne L. West, and George Maldonado Introduction 221 Clinical Problems to be Addressed by Pharmacoepidemiologic Research 221 Methodological Problems to be Solved by Pharmacoepidemiologic Research 222 Currently Available Solutions 233 The Future 242 Key Points 242 Further Reading 243 14 Assessing Causality from Case Reports 246
Bernard Bégaud and Judith K. Jones Introduction 246 Clinical Problems to be Addressed by Pharmacoepidemiologic Research 246 The Two Paradigms of Causality Assessment 246 When is Assessing Causation from Cases Reports Useful? 247 Methodological Problems to be Addressed by Pharmacoepidemiologic Research 248 Approaches for Assessing Causation from Individual Cases 249 Calibration 253 Choosing the Appropriate Approach 253 The Future 254 Key Points 255 Further Reading 255 15 Molecular Pharmacoepidemiology 257Christine Y. Lu and Stephen E. Kimmel Introduction 257 Definitions and Concepts 258 The Interface of Pharmacogenetics and Pharmacogenomics with Molecular Pharmacoepidemiology 259 Clinical Problems to be Addressed by Pharmacoepidemiologic Research 260 The Progression and Clinical Application of Molecular Pharmacoepidemiology 264 Methodological Problems to be Addressed by Pharmacoepidemiologic Research 264 Currently Available Solutions 269 The Future 271 Key Points 273 Further Reading 274 16 Bioethical Issues in Pharmacoepidemiologic Research 276Laura E. Bothwell, Annika Richterich, and Jeremy Greene Introduction 276 Clinical Problems to be Addressed by Pharmacoepidemiologic Research 276 Methodologic Problems to be Solved by Pharmacoepidemiologic Research 283 Currently Available Solutions 286 The Future 289 Acknowledgement 291 Key Points 291 Further Reading 293 17 The Use of Randomized Controlled Trials for Pharmacoepidemiology 294Samuel M. Lesko, Allen A. Mitchell, and Robert F. Reynolds Introduction 294 Clinical Problems to be Addressed by Pharmacoepidemiologic Research 294 Methodological Problems to be Solved by Pharmacoepidemiologic Research 296 Currently Available Solutions 298 Large Simple Trials 298 Analysis 303 Primary Analysis 303 The Future 304 Key Points 305 Further Reading 305 18 Pharmacoeconomics: Economic Evaluation of Pharmaceuticals 307
Kevin A. Schulman Introduction 307 Clinical Problems to be Addressed by Pharmacoeconomic Research 307 Methodological Problems to be Addressed by Pharmacoeconomic Research 312 The Future 320 Acknowledgements 320 Key Points 320 Further Reading 320 19 Patient Engagement and Patient Reported Outcomes 322Esi M. Morgan and Adam C. Carle Introduction 322 Patient Reported Outcomes in Clinical Trials 323 Patient Reported Outcomes in Routine Care 323 Patient Reported Outcomes as Motivation to Develop New Therapeutic Strategies 325 Clinical Problems to be Addressed by Pharmacoepidemiologic Research 326 Methodologic Problems to be Solved by Pharmacoepidemiologic Research 328 Currently Available Solutions 328 The Future 330 Key Points 331 Further Reading 331 20 The Use of Meta-analysis in Pharmacoepidemiology 334Brenda J. Crowe, Stephen J.W. Evans, H. Amy Xia, and Jesse A. Berlin Introduction 334 Clinical Problems to be Addressed by Pharmacoepidemiologic Research 335 Methodological Problems to be Solved by Pharmacoepidemiologic Research 336 Currently Available Solutions 338 The Future 350 Key Points 351 Further Reading 352 21 Studies of Medication Adherence 355
Julie Lauffenburger, Trisha Acri, and Robert Gross Introduction 355 Clinical Problems to be Addressed by Pharmacoepidemiologic Research 356 Methodological Problems to be Addressed by Pharmacoepidemiologic Research 357 Currently Available Solutions 357 Analysis Issues in Adherence 362 Use of Adherence Data in Clinical Trials and Comparative Effectiveness Studies 362 The Future 365 Key Points 365 Further Reading 366 22 Advanced Approaches to Controlling Confounding in Pharmacoepidemiologic Studies 368
Sebastian Schneeweiss and Samy Suissa Introduction 368 Clinical Problems to be Addressed by Pharmacoepidemiologic Research 368 Methodological Problems to be Addressed by Pharmacoepidemiologic Research 368 Currently Available Solutions 370 Conclusion 382 Key Points 382 Further Reading 384 Part IV Special Applications and the Future of Pharmacoepidemiology 387 23 Special Applications of Pharmacoepidemiology 389David Lee, Björn Wettermark, Christine Y. Lu, Stephen B. Soumerai, Robert T. Chen, Sharon-Lise T.Normand, Art Sedrakyan, Danica Marinac-Dabic, Daniel B. Horton, Sonia Hernandez-Diaz, Tamar Lasky, Krista F. Huybrechts, Claudia Manzo, Emil Cochino, Hanna M. Seidling, David W. Bates, Bennett Levitan, Rachael L. DiSantostefano, and Scott Evans Studies of Drug Utilization 389 Introduction 389 Evaluating and Improving Prescribing 398 Special Methodological Issues in Pharmacoepidemiologic Studies of Vaccine Safety 403 Epidemiologic Studies of Implantable Medical Devices 408 Research on the Effects of Medications in Pregnancy and in Children 418 Risk Management 427 The Pharmacoepidemiology of Medication Errors 436 Benefit-Risk Assessments of Medical Treatments 442 Further Reading 454 24 The Future of Pharmacoepidemiology 464
Brian L. Strom, Stephen E. Kimmel, and Sean Hennessy Introduction 464 The View from Academia 465 Scientific Developments 465 The View from Industry 471 The View from Regulatory Agencies 472 The View from the Law 473 Conclusion 473 Key Points 473 Further Reading 474 Appendix A - Sample Size Tables 475 Appendix B - Glossary 493 Index 505