S. Lori Brown, PhD, MPH. Epidemiologist. Epidemiology Branch. Division of Postmarket Surveillance. Center for Devices and Radiological Health. U.S. Food and Drug Administration. Rockville, MD, USA. Roselie A. Bright, ScD. Epidemiologist. Epidemiology Branch. Division of Postmarket Surveillance. Center for Devices and Radiological Health. U.S. Food and Drug Administration. Rockville, MD, USADale R. Tavris, MD, MPH. Epidemiologist. Epidemiology Branch. Division of Postmarket Surveillance. Center for Devices and Radiological Health. U.S. Food and Drug Administration. Rockville, MD, USA

"The first book to provide an overview of medical device epidemiology and surveillance … a very good exposition of how epidemiology can be used." (BMA Medical Book Competition - Programme and Award Winners, September 2008) "This book is unique, providing a comprehensive view of device surveillance and monitoring." (Doody's, March 2008)

• Foreword xiiiPreface xviiContributors xixAcknowledgments xxv1 Introduction 1Thomas P. Gross2 Medical device regulation in the USA 5Thomas P. Gross, Celia M. Witten, and Casper UldriksIntroduction 5Premarket review 6Marketing applications 8Postmarket oversight 10Conclusion 183 Medical device epidemiology 21Roselie A. Bright and S. Lori BrownIntroduction 21Features of medical devices that are relevant to epidemiology study design 26Study designs for medical device epidemiology 35Summary and recommendations 374 Surveillance of adverse medical device events 43Roselie A. BrightIntroduction 43Rationale for surveillance 44Surveillance based on adverse event reports 47Surveillance based on registries 52Active surveillance 53Necessary conditions for effective surveillance 54Ideal AMDE surveillance program 55Summary 585 The Medical Product Surveillance Network (MedSun) 63Roselie A. Bright, Marilyn N. Flack, and Susan N. GardnerHistorical motivation 63Initial considerations for the design of DeviceNet 64MedSun basic design 69Current status 71Is MedSun successful in promoting the safe use of medical devices? 74Epidemiologic considerations 75Summary 766 The National Electronic Injury Surveillance System (NEISS) and medical devices 79Brockton J. Hefflin, Thomas P. Gross, and Thomas J. SchroederDescription and history of NEISS 79Potential uses and limitations of NEISS 80Utilization of NEISS to produce national medical device-associated adverse event estimates 81Potential for long-term utilization of NEISS for medical device surveillance 837 Medical device nomenclature 87Brockton J. Hefflin, Thomas P. Gross, Elizabeth A. Richardson, and Vivian H. CoatesTechnical elements 87Current terminologies 91Applications of nomenclature 93Future developments 958 Data sources for medical device epidemiology studies and data mining 99Danica Marinac-Dabic, Baoguang Wang, Brockton J. Hefflin, Hesha J. Duggirala, Tripthi M. Mathew, and Cara J. KrulewitchIntroduction 99Data sources 100Surveillance databases 101Registries 105Automated large administrative databases 112National surveys 115Data mining 119Future use databases for medical device epidemiology 1209 Ethical requirements and guidelines for epidemiological studies of medical devices 127Danica Marinac-Dabic and Suzanne C. FitzpatrickIntroduction 127Bioethics foundations 128US government human subjects protection regulations 128HHS human subjects protection regulatory requirements 130FDA human subjects protection regulations 131Other professional ethical guidelines 133Ethical requirements for medical devices epidemiologic studies 136Future ethical requirements for epidemiologic studies 14210 An industry perspective: medical device epidemiology and surveillance 145Martha A. FeldmanIntroduction 145The product’s life cycle: premarket (preclinical and clinical) and postmarket (PM) studies 148Postmarket studies 153Summary 15611 Perspective from an academic on postmarket surveillance 159Lazar J. GreenfieldIntroduction 159Adverse event reporting 160Postmarket condition of approval studies and Section 522 studies 163Industry use of information from adverse event reports 165Academic opportunities 167Summary 16812 Perspective from a pharmacoepidemiologist 171Thomas K. HazletIntroduction 171Review of literature 171Contrasts with pharmacopeidemiology 173Conclusions 17513 Medical device regulation and surveillance: perspective from the EU 177Lennart PhilipsonIntroduction 177Medical devices: the European directives and definitions 178New approach 179Classification of medical devices in Europe 182Market surveillance 183Traceability of medical devices in Europe 184The vigilance system 18414 A consumer advocate’s perspective on medical device epidemiology and surveillance 187Diana M. ZuckermanExamples of widely publicized problems with selected medical devices 189Consumer concerns 193Regulatory mechanism recommendations 197Consumer group accomplishments: mixed results 19915 Pediatric Medical Device Use 203Judith U. Cope and Thomas P. GrossIntroduction 203Medical device use in children 204Special device risks and safety concerns for children 211Regulatory framework 212The future for pediatric medical device surveillance and epidemiology 21416 Selected medical devices used to manage diabetes mellitus 219Shewit Bezabeh, Joy H. Samuels-Reid, and Dale R. TavrisIntroduction 219Insulin delivery devices 221Continuous glucose monitoring devices 225Future medical devices for the management of diabetes 22817 Medical device-related outbreaks 237S. Lori Brown, Hesha J. Duggirala, and Dale R. TavrisIntroduction 237Endoscopes: bronchoscopes and gastrointestinal (GI) endoscopes 239Hemodialysis-related outbreaks 244Neonatal and pediatric intensive care units 247Miscellaneous device-related outbreaks 250Summary 25118 Risk of transmission of prions with medical devices 259S. Lori Brown and Azadeh ShoaibiIatrogenic transmission of prion disease via neurological or surgical instruments 260Surgical instruments used to transplant tissues known to have transmitted prion disease (corneal transplant) 261Surgical instruments in contact with lower risk peripheral tissues 262Decontaminating surgical instruments to reduce risk of TSE transmission 263FDA measures to minimize risk of transmission of BSE by medical products 267Summary 26819 Surveillance and epidemiology as tools for evaluating the materials used in medical devices 273Roselie A. BrightIntroduction 273General considerations that affect the design of epidemiologic studies of materials used in medical devices 273Example: natural rubber and latex allergy 279Summary 28620 Exploring methods for analyzing surveillance reports on electromagnetic interference with medical devices 291S. Lori Brown, Nilsa Loyo-Berríos, Michèle G. Bonhomme, Donald M. Witters, Nancy A. Pressly, and Jeffrey L. SilberbergElectromagnetic interference with medical devices 292The MAUDE database 292Adverse event reports to FDA (December 1984–October 1995): EMI with cardiovascular devices 293Adverse events reported to FDA (January 1994–March 2005): a recent epidemiological analysis 297Discussion 31121 Alternative and complementary medical devices 319S. Lori Brown and Joannie C. ShenIntroduction 319Acupuncture needles 322Ear candles 326Magnets 328Adverse events associated with alternative or complementary devices 33122 Drug-eluting coronary stents 335Hesha J. Duggirala, Thomas P. Gross, and David E. KandzariHistory and evolution of coronary stents: clinical perspective 335Novel drug-eluting stent programs 340Comparative trials of drug-eluting stents 342Application of drug-eluting stents in complex coronary lesion subsets 345Drug-eluting stents: regulatory perspective 34623 The treatment of abdominal aortic aneurysms 355Dale R. Tavris and Louis M. MessinaNatural history and indications for treatment 355FDA experience with the postmarket assessment of an endovascular graft 358Advances in stent-graft design and performance 361Conclusion 36324 Cardiovascular devices: aortic valves 367Ronald G. Kaczmarek and Chih-Hsin K. LiuIntroduction 367Operative mortality 370The FDA guidance for replacement valves and the objective performance criteria (OPC) 372Adverse event reports 373The need for epidemiological studies 373Conclusions 37625 Hemostasis Devices 379Dale R. Tavris, Beverly Gallauresi, and Ralph G. BrindisThe ideal vascular hemostasis device 380Origin of FDA concern with the postmarket performance of hemostasis devices 382FDA study to evaluate the risk associated with hemostasis device use 387Possible reasons for FDA findings of apparent protective effects of hemostasis devices 389Follow-up FDA study to assess the safety of hemostasis devices 389Conclusion 39026 ENT devices: cochlear implants 395James K. Kane and Eric A. MannCochlear implant description 395Epidemiological investigations involving meningitis associated with cochlear implants 396Conclusions 40527 Silicone gel-filled breast implants: surveillance and epidemiology 407S. Lori Brown and Joan Ferlo ToddBreast implant types 407A brief regulatory history of breast implants 409FDA surveillance studies on breast implants 411Summary 42128 Ophthalmic devices and clinical epidemiology 427Malvina B. Eydelman, Gene Hilmantel, James Saviola, and Don CalogeroIntroduction 427Epidemiological contributions to IOL evaluation 427Epidemiology of contact lens ulcers and public policy 430Conclusion 43729 Orthopedic devices: epidemiologic considerations 441Ronald G. Kaczmarek, Michele G. Bonhomme, Stanley A. Brown, Judith U. Cope, and Daniel S. McGunagleIntroduction 441Selected orthopedic materials 441Artificial hips 444Intervertebral disc replacement 452Data sources and selected methodological issues to consider in epidemiologic studies of orthopedic medical devices 456Summary 45830 Clinical epidemiology of intrapartum fetal monitoring devices 463Danica Marinac-Dabic, Barry S. Schifrin, Cara J. Krulewitch, and Roscoe M. MooreIntroduction 463Electronic fetal monitoring 464Scalp and umbilical cord blood gases analyses 470Fetal pulse oximetry 471Fetal ECG waveform monitoring 473Challenges of intrapartum fetal monitoring modalities 476Conclusion 47831 The postmarket surveillance of medical devices: meeting the challenge 483Susan N. Gardner and Daniel SchultzIndex 487

S. Lori Brown, PhD, MPH. Epidemiologist. Epidemiology Branch. Division of Postmarket Surveillance. Center for Devices and Radiological Health. U.S. Food and Drug Administration. Rockville, MD, USA. Roselie A. Bright, ScD. Epidemiologist. Epidemiology Branch. Division of Postmarket Surveillance. Center for Devices and Radiological Health. U.S. Food and Drug Administration. Rockville, MD, USADale R. Tavris, MD, MPH. Epidemiologist. Epidemiology Branch. Division of Postmarket Surveillance. Center for Devices and Radiological Health. U.S. Food and Drug Administration. Rockville, MD, USA

"The first book to provide an overview of medical device epidemiology and surveillance … a very good exposition of how epidemiology can be used." (BMA Medical Book Competition - Programme and Award Winners, September 2008) "This book is unique, providing a comprehensive view of device surveillance and monitoring." (Doody's, March 2008)

• Foreword xiiiPreface xviiContributors xixAcknowledgments xxv1 Introduction 1Thomas P. Gross2 Medical device regulation in the USA 5Thomas P. Gross, Celia M. Witten, and Casper UldriksIntroduction 5Premarket review 6Marketing applications 8Postmarket oversight 10Conclusion 183 Medical device epidemiology 21Roselie A. Bright and S. Lori BrownIntroduction 21Features of medical devices that are relevant to epidemiology study design 26Study designs for medical device epidemiology 35Summary and recommendations 374 Surveillance of adverse medical device events 43Roselie A. BrightIntroduction 43Rationale for surveillance 44Surveillance based on adverse event reports 47Surveillance based on registries 52Active surveillance 53Necessary conditions for effective surveillance 54Ideal AMDE surveillance program 55Summary 585 The Medical Product Surveillance Network (MedSun) 63Roselie A. Bright, Marilyn N. Flack, and Susan N. GardnerHistorical motivation 63Initial considerations for the design of DeviceNet 64MedSun basic design 69Current status 71Is MedSun successful in promoting the safe use of medical devices? 74Epidemiologic considerations 75Summary 766 The National Electronic Injury Surveillance System (NEISS) and medical devices 79Brockton J. Hefflin, Thomas P. Gross, and Thomas J. SchroederDescription and history of NEISS 79Potential uses and limitations of NEISS 80Utilization of NEISS to produce national medical device-associated adverse event estimates 81Potential for long-term utilization of NEISS for medical device surveillance 837 Medical device nomenclature 87Brockton J. Hefflin, Thomas P. Gross, Elizabeth A. Richardson, and Vivian H. CoatesTechnical elements 87Current terminologies 91Applications of nomenclature 93Future developments 958 Data sources for medical device epidemiology studies and data mining 99Danica Marinac-Dabic, Baoguang Wang, Brockton J. Hefflin, Hesha J. Duggirala, Tripthi M. Mathew, and Cara J. KrulewitchIntroduction 99Data sources 100Surveillance databases 101Registries 105Automated large administrative databases 112National surveys 115Data mining 119Future use databases for medical device epidemiology 1209 Ethical requirements and guidelines for epidemiological studies of medical devices 127Danica Marinac-Dabic and Suzanne C. FitzpatrickIntroduction 127Bioethics foundations 128US government human subjects protection regulations 128HHS human subjects protection regulatory requirements 130FDA human subjects protection regulations 131Other professional ethical guidelines 133Ethical requirements for medical devices epidemiologic studies 136Future ethical requirements for epidemiologic studies 14210 An industry perspective: medical device epidemiology and surveillance 145Martha A. FeldmanIntroduction 145The product’s life cycle: premarket (preclinical and clinical) and postmarket (PM) studies 148Postmarket studies 153Summary 15611 Perspective from an academic on postmarket surveillance 159Lazar J. GreenfieldIntroduction 159Adverse event reporting 160Postmarket condition of approval studies and Section 522 studies 163Industry use of information from adverse event reports 165Academic opportunities 167Summary 16812 Perspective from a pharmacoepidemiologist 171Thomas K. HazletIntroduction 171Review of literature 171Contrasts with pharmacopeidemiology 173Conclusions 17513 Medical device regulation and surveillance: perspective from the EU 177Lennart PhilipsonIntroduction 177Medical devices: the European directives and definitions 178New approach 179Classification of medical devices in Europe 182Market surveillance 183Traceability of medical devices in Europe 184The vigilance system 18414 A consumer advocate’s perspective on medical device epidemiology and surveillance 187Diana M. ZuckermanExamples of widely publicized problems with selected medical devices 189Consumer concerns 193Regulatory mechanism recommendations 197Consumer group accomplishments: mixed results 19915 Pediatric Medical Device Use 203Judith U. Cope and Thomas P. GrossIntroduction 203Medical device use in children 204Special device risks and safety concerns for children 211Regulatory framework 212The future for pediatric medical device surveillance and epidemiology 21416 Selected medical devices used to manage diabetes mellitus 219Shewit Bezabeh, Joy H. Samuels-Reid, and Dale R. TavrisIntroduction 219Insulin delivery devices 221Continuous glucose monitoring devices 225Future medical devices for the management of diabetes 22817 Medical device-related outbreaks 237S. Lori Brown, Hesha J. Duggirala, and Dale R. TavrisIntroduction 237Endoscopes: bronchoscopes and gastrointestinal (GI) endoscopes 239Hemodialysis-related outbreaks 244Neonatal and pediatric intensive care units 247Miscellaneous device-related outbreaks 250Summary 25118 Risk of transmission of prions with medical devices 259S. Lori Brown and Azadeh ShoaibiIatrogenic transmission of prion disease via neurological or surgical instruments 260Surgical instruments used to transplant tissues known to have transmitted prion disease (corneal transplant) 261Surgical instruments in contact with lower risk peripheral tissues 262Decontaminating surgical instruments to reduce risk of TSE transmission 263FDA measures to minimize risk of transmission of BSE by medical products 267Summary 26819 Surveillance and epidemiology as tools for evaluating the materials used in medical devices 273Roselie A. BrightIntroduction 273General considerations that affect the design of epidemiologic studies of materials used in medical devices 273Example: natural rubber and latex allergy 279Summary 28620 Exploring methods for analyzing surveillance reports on electromagnetic interference with medical devices 291S. Lori Brown, Nilsa Loyo-Berríos, Michèle G. Bonhomme, Donald M. Witters, Nancy A. Pressly, and Jeffrey L. SilberbergElectromagnetic interference with medical devices 292The MAUDE database 292Adverse event reports to FDA (December 1984–October 1995): EMI with cardiovascular devices 293Adverse events reported to FDA (January 1994–March 2005): a recent epidemiological analysis 297Discussion 31121 Alternative and complementary medical devices 319S. Lori Brown and Joannie C. ShenIntroduction 319Acupuncture needles 322Ear candles 326Magnets 328Adverse events associated with alternative or complementary devices 33122 Drug-eluting coronary stents 335Hesha J. Duggirala, Thomas P. Gross, and David E. KandzariHistory and evolution of coronary stents: clinical perspective 335Novel drug-eluting stent programs 340Comparative trials of drug-eluting stents 342Application of drug-eluting stents in complex coronary lesion subsets 345Drug-eluting stents: regulatory perspective 34623 The treatment of abdominal aortic aneurysms 355Dale R. Tavris and Louis M. MessinaNatural history and indications for treatment 355FDA experience with the postmarket assessment of an endovascular graft 358Advances in stent-graft design and performance 361Conclusion 36324 Cardiovascular devices: aortic valves 367Ronald G. Kaczmarek and Chih-Hsin K. LiuIntroduction 367Operative mortality 370The FDA guidance for replacement valves and the objective performance criteria (OPC) 372Adverse event reports 373The need for epidemiological studies 373Conclusions 37625 Hemostasis Devices 379Dale R. Tavris, Beverly Gallauresi, and Ralph G. BrindisThe ideal vascular hemostasis device 380Origin of FDA concern with the postmarket performance of hemostasis devices 382FDA study to evaluate the risk associated with hemostasis device use 387Possible reasons for FDA findings of apparent protective effects of hemostasis devices 389Follow-up FDA study to assess the safety of hemostasis devices 389Conclusion 39026 ENT devices: cochlear implants 395James K. Kane and Eric A. MannCochlear implant description 395Epidemiological investigations involving meningitis associated with cochlear implants 396Conclusions 40527 Silicone gel-filled breast implants: surveillance and epidemiology 407S. Lori Brown and Joan Ferlo ToddBreast implant types 407A brief regulatory history of breast implants 409FDA surveillance studies on breast implants 411Summary 42128 Ophthalmic devices and clinical epidemiology 427Malvina B. Eydelman, Gene Hilmantel, James Saviola, and Don CalogeroIntroduction 427Epidemiological contributions to IOL evaluation 427Epidemiology of contact lens ulcers and public policy 430Conclusion 43729 Orthopedic devices: epidemiologic considerations 441Ronald G. Kaczmarek, Michele G. Bonhomme, Stanley A. Brown, Judith U. Cope, and Daniel S. McGunagleIntroduction 441Selected orthopedic materials 441Artificial hips 444Intervertebral disc replacement 452Data sources and selected methodological issues to consider in epidemiologic studies of orthopedic medical devices 456Summary 45830 Clinical epidemiology of intrapartum fetal monitoring devices 463Danica Marinac-Dabic, Barry S. Schifrin, Cara J. Krulewitch, and Roscoe M. MooreIntroduction 463Electronic fetal monitoring 464Scalp and umbilical cord blood gases analyses 470Fetal pulse oximetry 471Fetal ECG waveform monitoring 473Challenges of intrapartum fetal monitoring modalities 476Conclusion 47831 The postmarket surveillance of medical devices: meeting the challenge 483Susan N. Gardner and Daniel SchultzIndex 487