Textbook of Pharmacoepidemiology 3rd Edition PDF

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
Pharmacoepidemiology Versus Clinical Pharmacology 4
Pharmacoepidemiology Versus Epidemiology 5
Historical
Background 5
Early Legislation 5
Drug Crises and Resulting Regulatory Actions 7
Legislative Actions Resulting from Drug Crises 9
Intellectual Development of Pharmacoepidemiology Emerging from Drug Crises 10
The
Current Drug Approval Process 13
Drug Approval in the US 13
Drug Approval in Other Countries 14
Potential
Contributions of Pharmacoepidemiology 15
Supplementary Information 16
New Types of Information Not Available from Premarketing Studies 17
General Contributions of Pharmacoepidemiology 17
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
Case Reports 26
Case Series 26
Analyses of Secular Trends 27
Case–Control Studies 28
Cohort Studies 28
Analysis of Case–Control and Cohort Studies 29
Randomized Clinical Trials 30
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
Absorption 49
Volume of Distribution 49
Metabolism 49
Elimination 51
Special
Populations 52
Elderly 52
Pediatrics 53
Pregnancy 55
Organ Impairment 55
Drug Interactions 56
Pharmacodynamics
56
Overview 57
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
Regulatory 63
Marketing 64
Legal 65
Clinical 66
Safety
Versus Risk 67
Risk
Tolerance 67
Features of the Adverse Outcome 68
Characteristics of the Exposure 68
Perceptions of the Evaluator 69
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
Introduction 73
The Drug Approval Process 74
Prescribing Practices 75
Evaluation of Patients’ Use of Drugs in the Health Care System 76
Assessment of the Quality and Outcomes of Medication Use in Populations 76
Policy Analysis 77
Interventional Pharmacoepidemiology 77
Economic Assessment of Medication-Related
Issues 78
The Academic Medical Center 78
Consortia of Academic Medical Center Programs for Pharmacoepidemiologic
Research 78
The Future 79
Summary Points for the View from Academia 79
The
View from Industry 81
Introduction 81
Regulatory and Industry Focus on Risk Management and Epidemiology 81
Epidemiology in Drug Safety Evaluation 83
Epidemiology in Evaluation of Risk Mitigation Interventions 86
Conclusion 87
Summary Points for the View from Industry 88
The
View from Regulatory Agencies 90
Introduction 90
Assessing the Need for Medicines 91
Orphan Drugs 91
Planning Drug Development Programs 92
Pre-approval
Review of Clinical Safety Data 93
Planning for Post-approval
Studies 94
Monitoring Post-approval
Safety 94
Assessing Actual Use Patterns of a Medicine 95
Assessing Impact of Regulatory Actions 95
Advancing the Science of Pharmacoepidemiology 96
Conclusion 97
Summary Points for the View from Regulatory Agencies 97
The
View from the Legal System 98
Introduction 98
Tort Law and Product Liability Lawsuits 98
Pharmacoepidemiology and Contract Law 102
Pharmacoepidemiology and Intellectual Property Law 103
Conclusion 105
Summary Points for the View from the Legal System 105
Further Reading 107
The View from Academia 107
The View from Industry 108
The View from Regulatory Agencies 109
The View from the Legal System 110
Contract-Related
Issues in Pharmacoepidemiology 110
Patent Law and Pharmacoepidemiology 110
Part II Sources of Pharmacoepidemiology Data 113
7 Postmarketing Spontaneous Pharmacovigilance Reporting Systems 115
Gerald J. Dal Pan, Marie Lindquist, and Kate Gelperin
Introduction
115
Description
116
Adverse Events and Adverse Drug Reactions 116
Overview of Pharmacovigilance Reporting Systems 117
The Concept of Spontaneous AE/ADR Reporting 118
Report Characteristics 119
Social Media 121
National Pharmacovigilance Systems 121
National and International Postmarketing Adverse Event Databases 123
Detecting Signals from a Postmarketing Adverse Event Database 124
Review of Individual Case Safety Reports 126
Reporting Ratios 127
Strengths
128
Signal Detection 128
Opportunity for the Public to Report AEs/ADRs 129
Scope 129
Limitations
129
Quality of Reports 129
Underreporting 130
Non-uniform
Temporal Trends in Reporting 130
Particular
Applications 131
Case Series and Reporting Rates 131
Data Mining Signals 131
Signals from Developing Countries 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
Claims and Other Administrative Databases 137
Electronic Health Record Databases 138
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
Attributes of Encounter Databases 145
Selected Encounter Databases 149
Strengths
161
Limitations
162
Particular
Applications 163
Typical Activities Involved in Studies Using Encounter Databases 163
Deciding Between Individual Encounter Databases 164
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
Overview of Health Care Systems and Populations 174
Overview of Databases 181
Data Collection and Structure 182
Data Quality: Accuracy and Completeness 183
Data Access for Researchers 184
Strengths
184
Population-Based Data, Sample Size, and Length of Follow-up 184
Validity of Clinical Information 184
Accuracy of Drug Information 184
Ability to Access Original Health Records 184
Linkage to External Patient-Level
Data 185
Limitations
185
Incompleteness of Clinical Data 185
Incompleteness of Drug Data 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
Research Questions that Require Primary Data 192
Hybrid or Enriched Designs 195
Methods
of Primary Data Collection 195
Site-Based Data Collection 195
Clinician or Site-Reported
Outcomes (ClinROs) 195
Patient-Generated
Data 196
Registries as Means of Data Collection 196
Biobanks/Specimen Banks 197
Guidelines on the Quality of Data Collection 197
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 203
Brian L. Strom
Introduction
203
Choosing
Among the Available Approaches to Pharmacoepidemiologic
Studies 203
Comparative Characteristics of Pharmacoepidemiologic Data Resources 208
Characteristics of Research Questions and their Impact on the Choice
of Pharmacoepidemiologic Data Resources 211
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 221
Mary 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
Indices of Measurement Error Relevant to Pharmacoepidemiologic Research 222
Quantitative Measurement of Validity 222
Quantitative Measurement of Reliability 224
Measurement Error in Pharmacoepidemiologic Research 225
Adjusting Measures of Association for Measurement Error 227
Self-Reported
Drug Data from Ad hoc Survey Studies: Recall Accuracy 228
The Influence of Medication Class 228
The Influence of Questionnaire Design 228
The Influence of Patient Population 229
Self-Reported
Diagnosis and Hospitalization Data from Ad hoc Studies: Recall Accuracy 230
The Influences of Medical Condition Type 230
The Influences of Timing of Diagnosis and Its Emotional Effects on the Patient 230
The Influence of Patient Population 232
The Influence of Questionnaire Design 232
Currently
Available Solutions 233
Following Best Practices for Questionnaire Design 233
Developing a De novo Questionnaire 233
Conducting Validation Studies to Assess Self-Reported
Data 235
Considering the Influence of Comparator Selection on Validation Studies 235
Validation of Pharmacoepidemiologic Drug and Diagnosis Data from Electronic Encounter
Databases 236
Special Considerations with Drug Data 237
Special Considerations with Diagnosis and Hospitalization Data 237
Special Considerations with Distributed Data Systems 239
Best Practices 239
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
Spontaneous Reporting 247
Clinical Trials and Pharmacoepidemiology 248
Clinical Practice and Prescription 248
Reports of Adverse Drug Reactions to Medical Journals 248
Hypothesis Generation and Research 248
Methodological
Problems to be Addressed by Pharmacoepidemiologic Research 248
Approaches
for Assessing Causation from Individual Cases 249
Expert Judgment/Global Introspection 249
Structured Guidelines and Algorithms 250
Probabilistic Approaches 251
Calibration
253
Choosing
the Appropriate Approach 253
The
Future 254
Key
Points 255
Further
Reading 255
15 Molecular Pharmacoepidemiology 257
Christine Y. Lu and Stephen E. Kimmel
Introduction
257
Definitions
and Concepts 258
Genetic Variability 258
Pharmacogenetics and Pharmacogenomics 259
The
Interface of Pharmacogenetics and Pharmacogenomics with Molecular
Pharmacoepidemiology 259
Clinical
Problems to be Addressed by Pharmacoepidemiologic Research 260
Three Ways That Genes Can Affect Drug Response 260
The Interplay of Various Mechanisms 263
The
Progression and Clinical Application of Molecular Pharmacoepidemiology 264
Methodological
Problems to be Addressed by Pharmacoepidemiologic Research 264
Interactions 266
Type I Error 267
Type II Error 267
Confounding by Population Admixture 268
Currently
Available Solutions 269
Identifying Additional Genetic Contributions to Drug Response 269
Interactions 270
Type I Error and Replication 270
Type II Error 271
Confounding by Population Admixture 271
The
Future 271
Key
Points 273
Further Reading 274
16 Bioethical Issues in Pharmacoepidemiologic Research 276
Laura E. Bothwell, Annika Richterich, and Jeremy Greene
Introduction
276
Clinical
Problems to be Addressed by Pharmacoepidemiologic Research 276
The Emergence, Changing Methods, and Moral Stakes of Pharmacoepidemiology in
Twentieth Century North America 276
European Pharmacoepidemiologic Trends and Ethics 280
East Asian Pharmacoepidemiologic Trends and Ethics 282
Methodologic
Problems to be Solved by Pharmacoepidemiologic Research 283
Informed Consent 284
Ethics of Surveillance 285
Ethical Benefits of Pharmacoepidemiologic Research for Data Integrity 285
Problems of Conflicts of Interest for Drug Industry Research 286
Currently
Available Solutions 286
Good Pharmacoepidemiology and Pharmacovigilance Practices 286
Protections against Conflicts of Interest for Drug Industry-Sponsored
Research 288
The
Future 289
Acknowledgement 291
Key
Points 291
Further Reading 293
17 The Use of Randomized Controlled Trials for Pharmacoepidemiology 294
Samuel 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
Overview of Classic RCTs 296
Limitations of RCTs 298
Currently
Available Solutions 298
Large Simple Trials 298
When is an LST Feasible? 301
Logistics of Conducting an LST 302
Analysis
303
Primary Analysis 303
Subgroup Analyses 303
Data Monitoring/Interim Analyses 304
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
The Economics of Drug Development 307
Health Economics and Health Care Financing 308
Methodological
Problems to be Addressed by Pharmacoeconomic Research 312
Types of Analysis 312
Types of Costs 315
Perspective of Analysis 316
Using Economic Data 317
The
Future 320
Acknowledgements 320
Key
Points 320
Further Reading 320
19 Patient Engagement and Patient Reported Outcomes 322
Esi 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
Ensuring PRO Completion and Results Review 326
PRO Selection, Score Interpretation and Interventions 326
Patient Engagement and Individualized Assessment and Treatment Plans 327
Barriers to Measuring PROs in Clinical Practice and Using PROs to Guide
Interventions 327
Methodologic
Problems to be Solved by Pharmacoepidemiologic Research 328
Currently
Available Solutions 328
Discordance in Perspectives between Patients, Clinicians and Researchers 328
Measuring within Person Change 329
Selection of Patient Reported Outcomes and Implementation into Practice 330
The
Future 330
Key Points 331
Further Reading 331
20 The Use of Meta-analysis in Pharmacoepidemiology 334
Brenda 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
Susceptibility of the Original Studies to Bias 336
Combinability of Studies 336
Publication Bias 337
Bias in the Abstraction of Data 338
Currently
Available Solutions 338
Steps Involved in Performing a Meta-analysis
338
Publication Bias 344
Indirect Comparison and Simultaneous Comparison of Treatments Available for Specific
Conditions 346
Case Studies of Applications of Meta-analysis
346
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
Selecting Adherence Intervals 362
Statistical Analysis 363
Time-Varying
Nature of Adherence and Trajectory Modeling 364
Prediction of Adherence for Interventions 365
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
Efficient Sampling Designs within a Cohort Study 370
Analytic Approaches for Improved Confounding Control 377
Conclusion
382
Key
Points 382
Further Reading 384
Part IV Special Applications and the Future of Pharmacoepidemiology 387
23 Special Applications of Pharmacoepidemiology 389
David 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
Clinical Problems to be Addressed by Pharmacoepidemiologic Research 391
Methodological Problems to be Addressed by Pharmacoepidemiologic Research 392
Examples of Currently Available Solutions 393
The Future 396
Key Points for Studies of Drug Utilization 396
Evaluating
and Improving Prescribing 398
Clinical Problems to be Addressed by Pharmacoepidemiologic Research 398
Methodological Problems to be Addressed by Pharmacoepidemiologic Research 398
Examples of Currently Available Solutions 399
The Future 402
Key Points for Evaluating and Improving Prescribing 402
Special
Methodological Issues in Pharmacoepidemiologic Studies of Vaccine Safety 403
Clinical Problems to be Addressed by Pharmacoepidemiologic Research 403
Methodological Problems to be Addressed by Pharmacoepidemiologic Research 404
Examples of Currently Available Solutions 407
The Future 408
Key Points for Special Methodological Issues in Pharmacoepidemiologic Studies of Vaccine
Safety 408
Epidemiologic
Studies of Implantable Medical Devices 408
What Is a Medical Device and how Is it Different from a Drug? 409
Clinical Problems to be Addressed by Medical Device Epidemiologic Research 409
Methodological Problems to be Solved by Medical Device Epidemiologic Research 410
Examples of Currently Available Solutions 412
The Future 415
Key Points for Epidemiologic Studies of Devices 418
Research
on the Effects of Medications in Pregnancy and in Children 418
Clinical Problems to be Addressed by Pharmacoepidemiologic Research 418
Methodological Problems to be Solved by Pharmacoepidemiologic Research 419
Examples of Currently Available Solutions 423
The Future 424
Key Points for Research on the Effects of Medications in Pregnancy and in Children 426
Risk
Management 427
Clinical Problems to be Addressed by Pharmacoepidemiologic Research 428
Methodological Problems to be Addressed by Pharmacoepidemiologic Research 433
Examples of Currently Available Solutions 434
The Future 434
Key Points for Risk Management 436
The
Pharmacoepidemiology of Medication Errors 436
Safety Theory 436
Patient Safety Concepts as Applied to Pharmacoepidemiology 437
Clinical Problems to be Addressed by Pharmacoepidemiologic Research 438
Methodological Problems to be Addressed by Pharmacoepidemiologic Research 441
The Future 442
Key Points for the Pharmacoepidemiology of Medication Errors 442
Benefit–
Risk Assessments of Medical Treatments 442
Clinical Problems to be Addressed by Pharmacoepidemiologic Research 443
Methodological Problems to be Addressed by Pharmacoepidemiologic Research 443
Examples of Currently Available Solutions 444
The Future 451
Key Points for Benefit-Risk Assessments of Medical Treatments 454
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
Funding 469
Personnel 470
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
Textbook of Pharmacoepidemiology 3rd Edition PDF Ebook

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.