National Academies Press: OpenBook
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R1
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R2
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R3
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R4
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R5
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R6
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R7
Page viii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R8
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R9
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R10
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R11
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R12
Page xiii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R13
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R14
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R15
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R16
Page xvii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R17
Page xviii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R18
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R19
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2019. Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series. Washington, DC: The National Academies Press. doi: 10.17226/25352.
×
Page R20

Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Examining the Impact of Real-World Evidence on Medical Product Development PROCEEDINGS OF A WORKSHOP SERIES Erin Hammers Forstag, Benjamin Kahn, Amanda Wagner Gee, and Carolyn Shore, Rapporteurs Forum on Drug Discovery, Development, and Translation Board on Health Sciences Policy Health and Medicine Division P REP UBLI CATI ON COP Y: UN CORR ECTED P ROOFS

THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001 This activity was supported by contracts between the National Academy of Sciences and AbbVie Inc.; American Diabetes Association; Amgen Inc. (Contract No. GHCCOPS-CSARF-126570); Association of American Medical Colleges; AstraZeneca; Burroughs Wellcome Fund (Contract No. 1017664); Critical Path Institute; Eli Lilly and Company; FasterCures; Foundation for the National Institutes of Health; Friends of Cancer Research; GlaxoSmithKline; Johnson & Johnson; Merck & Co., Inc. (Contract No. CMO180308-0002499); National Institutes of Health (Contract No. Contract No. HHSN263201200074I; Task Order No. HHSN26300093): National Cancer Institute, National Center for Advancing Translational Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, Office of the Director; New England Journal of Medicine; Pfizer Inc.; Sanofi (Contract No. 33215505); Takeda Pharmaceuticals (Contract No. 53108); and the U.S. Food and Drug Administration (Grant No. 5R13FD005496-04 and Contract No. HHSP2233201400020B, Order No. HHSP23337055): Center for Drug Evaluation and Research, Office of the Commissioner. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project. International Standard Book Number-13: 978-0-309-XXXXX-X International Standard Book Number-10: 0-309-XXXXX-X Digital Object Identifier: https://doi.org/10.17226/25352 Additional copies of this publication are available from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu. Copyright 2019 by the National Academy of Sciences. All rights reserved. Printed in the United States of America Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2019. Examining the impact of real-world evidence on medical product development: Proceedings of a workshop series. Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/25352. P REP UBLI CATI ON COP Y: UN CORR ECTED P ROOFS

The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president. The National Academy of Engineering was established in 1964 under the charter of the National Academy of Sciences to bring the practices of engineering to advising the nation. Members are elected by their peers for extraordinary contributions to engineering. Dr. C. D. Mote, Jr., is president. The National Academy of Medicine (formerly the Institute of Medicine) was established in 1970 under the charter of the National Academy of Sciences to advise the nation on medical and health issues. Members are elected by their peers for distinguished contributions to medicine and health. Dr. Victor J. Dzau is president. The three Academies work together as the National Academies of Sciences, Engineering, and Medicine to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The National Academies also encourage education and research, recognize outstanding contributions to knowledge, and increase public understanding in matters of science, engineering, and medicine. Learn more about the National Academies of Sciences, Engineering, and Medicine at www.nationalacademies.org. P REP UBLI CATI ON COP Y: UN CORR ECTED P ROOFS

Consensus Study Reports published by the National Academies of Sciences, Engineering, and Medicine document the evidence-based consensus on the study’s statement of task by an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on information gathered by the committee and the committee’s deliberations. Each report has been subjected to a rigorous and independent peer-review process and it represents the position of the National Academies on the statement of task. Proceedings published by the National Academies of Sciences, Engineering, and Medicine chronicle the presentations and discussions at a workshop, symposium, or other event convened by the National Academies. The statements and opinions contained in proceedings are those of the participants and are not endorsed by other participants, the planning committee, or the National Academies. For information about other products and activities of the National Academies, please visit www.nationalacademies.org/about/whatwedo. P REP UBLI CATI ON COP Y: UN CORR ECTED P ROOFS

PLANNING COMMITTEE ON EXAMINING THE IMPACT OF REAL-WORLD EVIDENCE ON MEDICAL PRODUCT DEVELOPMENT 1 MARK MCCLELLAN (Co-Chair), Robert J. Margolis Professor of Business, Medicine, and Policy, and Director, Duke-Margolis Center for Health Policy, Duke University GREGORY SIMON (Co-Chair), Senior Investigator, Kaiser Permanente Washington Health Research Institute JEFF ALLEN, President and Chief Executive Officer, Friends of Cancer Research ANDREW BINDMAN, Professor of Medicine, Epidemiology, and Biostatistics, University of California, San Francisco JOHN GRAHAM, Senior Vice President, Medical Engagement and Value Evidence & Outcomes, GlaxoSmithKline (from March 2018) ADAM HAIM, Chief, Treatment and Preventive Intervention Research Branch, National Institute of Mental Health, National Institutes of Health MICHAEL HORBERG, Executive Director, Research, Community Benefit, and Medicaid Strategy, Mid- Atlantic Permanente Medical Group, and Director, Mid-Atlantic Permanente Research Institute PETRA KAUFMANN, Director, Office of Rare Diseases Research and Division of Clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health (until May 2018) RICHARD KUNTZ, Senior Vice President and Chief Scientific, Clinical & Regulatory Officer, Medtronic, Inc. ELLIOT LEVY, Senior Vice President, Global Development, Amgen Inc. DAVID MADIGAN, Professor of Statistics, and Dean, Faculty of Arts and Sciences, Columbia University DEVEN MCGRAW, Chief Regulatory Officer, Ciitizen JOHN DAVID NOLEN, Physician Executive, Clinical Strategy, Cerner Corporation (until October 2017) RICHARD PLATT, Professor and Chair, Department of Population Medicine, and Executive Director, Harvard Pilgrim Health Care Institute, Harvard Medical School PATRICK VALLANCE, President, Research and Development, GlaxoSmithKline (until March 2018) JOANNE WALDSTREICHER, Chief Medical Officer, Johnson & Johnson MARCUS WILSON, Co-Founder and President, HealthCore, Inc. Health and Medicine Division Staff CAROLYN SHORE, Senior Program Officer (from August 2017) ANNE CLAIBORNE, Senior Program Officer (until August 2017) AMANDA WAGNER GEE, Program Officer BEN KAHN, Associate Program Officer (from October 2017) JONATHAN PHILLIPS, Associate Program Officer (until October 2017) MELVIN JOPPY, Senior Program Assistant ANDREW M. POPE, Director, Board on Health Sciences Policy Consultant ERIN HAMMERS FORSTAG, Science Writer 1 The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published Proceedings of a Workshop Series rests with the workshop rapporteurs and the institution. P REP UBLI CATI ON COP Y: UN CORR ECTED P ROOFS v

FORUM ON DRUG DISCOVERY, DEVELOPMENT, AND TRANSLATION 1 RUSS B. ALTMAN (Co-Chair), Kenneth Fong Professor of Bioengineering, Genetics, Medicine, and (by courtesy) Computer Science, Stanford University ROBERT M. CALIFF (Co-Chair), Vice Chancellor for Health Data Science, Duke University, and Scientific Advisor, Verily Life Sciences CHRISTOPHER P. AUSTIN, Director, National Center for Advancing Translational Sciences, National Institutes of Health LINDA BRADY, Director, Division of Neuroscience and Basic Behavioral Science, National Institute of Mental Health, National Institutes of Health TANISHA CARINO, Executive Director, FasterCures RICHARD DAVEY, Deputy Clinical Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health JAMES H. DOROSHOW, Deputy Director, Clinical and Translational Research, National Cancer Institute, National Institutes of Health JEFFREY M. DRAZEN, Editor-in-Chief, New England Journal of Medicine STEVEN K. GALSON, Senior Vice President, Global Regulatory Affairs and Safety, Amgen Inc. CARLOS GARNER, Vice President, Global Regulatory Affairs, Eli Lilly and Company JULIE L. GERBERDING, Chief Patient Officer and Executive Vice President, Strategic Communications, Global Public Policy, and Population Health, Merck & Co., Inc. LYNN D. HUDSON, Chief Science Officer, Critical Path Institute JEFF HURD, Regional Clinical Account Director, AstraZeneca S. CLAIBORNE JOHNSTON, Dean, Dell Medical School, The University of Texas at Austin KATHARINE KNOBIL, Chief Medical Officer, GlaxoSmithKline FREDA C. LEWIS-HALL, Executive Vice President & Chief Medical Officer, Pfizer Inc. ALLISON MCELVAINE, Vice President, Research & Scientific Programs, American Diabetes Association ROSS MCKINNEY, JR., Chief Scientific Officer, Association of American Medical Colleges JOSEPH P. MENETSKI, Deputy Director, Research Partnerships, Foundation for the National Institutes of Health BERNARD H. MUNOS, Founder, Innothink Center for Research in Biomedical Innovation MICHAEL SEVERINO, Executive Vice President, Research & Development, and Chief Scientific Officer, AbbVie Inc. RACHEL E. SHERMAN, Principal Deputy Commissioner, Office of the Commissioner, U.S. Food and Drug Administration ELLEN V. SIGAL, Chair and Founder, Friends of Cancer Research LANA R. SKIRBOLL, Vice President, Science Policy, Sanofi BRIAN L. STROM, Chancellor, Rutgers Biomedical and Health Sciences, Rutgers University AMIR TAMIZ, Director, Division of Translational Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health PAMELA TENAERTS, Executive Director, Clinical Trials Transformation Initiative, Duke University JOHN WAGNER, Senior Vice President and Head of Clinical and Translational Sciences, Takeda Pharmaceuticals JOANNE WALDSTREICHER, Chief Medical Officer, Johnson & Johnson CARRIE WOLINETZ, Associate Director of Science Policy, Office of Science Policy, National Institutes of Health 1 The National Academies of Sciences, Engineering, and Medicine’s forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published Proceedings of a Workshop Series rests with the workshop rapporteurs and the institution. P REP UBLI CATI ON COP Y: UN CORR ECTED P ROOFS vii

JANET WOODCOCK, Director, Center for Drug Evaluation and Research, U.S. Food and Drug Administration Forum Staff CAROLYN SHORE, Forum Director REBECCA ENGLISH, Program Officer AMANDA WAGNER GEE, Program Officer SYLVIA NCHA, Associate Program Officer EESHAN KHANDEKAR, Research Associate MELVIN JOPPY, Senior Program Assistant ANDREW M. POPE, Director, Board on Health Sciences Policy P REP UBLI CATI ON COP Y: UN CORR ECTED P ROOFS viii

REVIEWERS This Proceedings of a Workshop Series was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process. We thank the following individuals for their review of this proceedings: DEBORAH ASHBY, Imperial College London JENNIFER GRAFF, National Pharmaceutical Council PALL JONSSON, National Institute for Health and Care Excellence (UK) SARAH LEATHERMAN, Department of Veterans Affairs Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings nor did they see the final draft before its release. The review of this proceedings was overseen by DAN MASYS, University of Washington. He responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteurs and the National Academies. P REP UBLI CATI ON COP Y: UN CORR ECTED P ROOFS ix

CONTENTS BOXES, FIGURES, AND TABLES xiii ACRONYMS AND ABBREVIATIONS xvii 1 INTRODUCTION 1 Defining the Terms, 5 U.S. Food and Drug Administration Vision for the Future, 6 Fit-for-Purpose Evidence, 8 2 PERSPECTIVES ON REAL-WORLD EVIDENCE 11 Payer Perspective, 12 Delivery Systems Perspective, 13 Patient Perspective, 15 Discussion, 17 3 LEARNING FROM SUCCESS 21 Salford Lung Studies, 22 Sentinel, 26 Device Registries, 29 4 BARRIERS AND DISINCENTIVES TO THE USE OF REAL-WORLD EVIDENCE AND REAL-WORLD DATA 31 The Use of Real-World Evidence and Real-World Data in Product Development, 32 Making Choices About Research Design, 33 Accelerating Evidence Generation Through Defragmentation, 34 Evidence Hierarchies, 36 Opportunities to Integrate Real-World Data and Real-World Evidence in Research, 37 Discussion, 39 5 GETTING UNSTUCK: MYTHBUSTING THE CURRENT SYSTEM 41 From Precision to Reliability, 42 Integrating the New with the Old, 45 Regulatory Perspective, 51 6 WHEN IS A REAL-WORLD DATA ELEMENT FIT FOR ASSESSMENT OF ELIGIBILITY, TREATMENT EXPOSURE, OR OUTCOMES? 55 Real-World Data Elements, 56 Illustrative Examples, 57 Discussion: Characterizing Real-World Data and Real-World Evidence, 61 Decision Aid, 63 “Fit for Purpose” and Relevance of Data, 66 Patient-Generated Data, 69 Discussion: Real-World Data Concerns for Future Research, 72 P REP UBLI CATI ON COP Y: UN CORR ECTED P ROOFS xi

7 HOW TIGHTLY SHOULD INVESTIGATORS ATTEMPT TO CONTROL OR RESTRICT TREATMENT QUALITY IN A PRAGMATIC OR “REAL-WORLD” TRIAL? 77 Illustrative Examples, 78 Decision Aid, 84 Patient-Centered Research, 86 Context of the Decision, 87 Obligations to Patients, 88 8 OBSCURING INTERVENTION ALLOCATION IN TRIALS TO GENERATE REAL-WORLD EVIDENCE: WHY, WHO, AND HOW? 91 Illustrative Examples, 92 Decision Aid, 95 Discussion, 97 9 GAINING CONFIDENCE IN OBSERVATIONAL COMPARISONS 103 Illustrative Examples, 104 Discussion: Observational Studies and Randomization, 110 Decision Aid, 113 Presentations: Observational Studies and Bias, 114 Discussion: The Future of Observational Studies, 117 10 LOOKING AHEAD 119 Real-World Evidence to Improve Health Technology Assessment, 120 Real-World Evidence to Turn Patients into Partners, 122 Real-World Evidence to Transform Research and Development, 124 Real-World Evidence to Inform Regulatory Decisions, 128 Final Thoughts, 135 REFERENCES 139 APPENDIXES A Related Resources 145 B Workshop One Agenda 147 C Workshop Two Agenda 155 D Workshop Three Agenda 161 P REP UBLI CATI ON COP Y: UN CORR ECTED P ROOFS xii

Boxes, Figures, and Tables BOXES 1-1 Workshop Series Statement of Task, 2 1-2 Definitions of Real-World Data and Real-World Evidence from Various Stakeholders, 6 4-1 Barriers to Adoption of Real-World Evidence and Real-World Data in Research as Discussed by Individual Workshop Participants, 36 5-1 A Patient’s Perspective on Randomized Controlled Trials as Presented by McCollister- Slipp, 45 6-1 Feedback on the Decision Aid as Discussed by Individual Workshop Participants, 65 6-2 The Importance of Patient-Generated Data as Discussed by Individual Workshop Participants, 71 6-3 Potential Sources of Bias in Real-World Data as Discussed by Individual Workshop Participants, 73 7-1 Patient Compliance as Discussed by Individual Workshop Participants, 84 7-2 Regulatory Decision Making Regarding Clinical Strategy as Discussed by Schneeweiss, 88 8-1 Other Examples of Blinded and Non-Blinded Studies Discussed Throughout the Workshop Series as Presented by Individual Workshop Participants, 94 8-2 Feedback on the Decision Aid as Discussed by Individual Workshop Participants, 97 9-1 Feedback on the Decision Aid as Discussed by Individual Workshop Participants, 114 10-1 Key Messages Identified by Individual Speakers, 135 FIGURES 2-1 Platform for engaging everyone responsibly (PEER), 17 P REP UBLI CATI ON COP Y: UNCORR ECTED P ROOFS xiii

XIV EXAMINING THE IMPACT OF RWE ON MEDICAL PRODUCT DEVELOPMENT 3-1 Salford Lung Studies design, 23 3-2 Salford Lung Studies platform diagram, 24 3-3 Data elements available in Sentinel, 27 4-1 The importance of integrated data, 35 4-2 Transformation from traditional to new approach of evidence generation, 37 4-3 Mosaic methodologies to blend randomized controlled trial (RCT) and real-world evidence (RWE) approaches, 38 5-1 Learning health care system, 44 5-2 Broad sources of real-world data and broad uses of real-world evidence, 46 5-3 Effect estimates from published observational studies on antidepressants and the risk of preeclampsia, 49 5-4 Effect estimates from published observational studies on all disease states, all treatments, and all causal effects, 50 5-5 Systematically generated evidence from observational data, comparing all depression treatments on all outcomes of interest, 51 6-1 Possible sources of real-world data, 56 6-2 Real-world overall survival, 60 6-3 Real-world data decision aid, 64 6-4 Decision tree to identify possible data sources, 67 6-5 Linked, de-identified data sources at OptumLabs, 68 6-6 Decision process with an existing real-world data asset, 69 6-7 Effect of medical procedure or surgery on resting heart rate, 71 7-1 Cumulative probability of experiencing a significant suicide attempt or hospitalization to prevent suicide, 83 7-2 Decision aid on questions to consider regarding participant safety and investigator control of treatments in trial taking place in a community care setting, 85 7-3 Features of the ArthritisPower research registry, with smartphone application and user- friendly interface, 86 8-1 Study design for the INVESTED trial, 93 8-2 Decision aid on questions to consider regarding when and whether to obscure intervention allocation (commonly known as blinding) in trials intended to generate real- world evidence, 96 8-3 Considerations around uncertainty in study design, 98 8-4 Blinding not warranted when usage factors are unknown, 99 9-1 Sources of data for research, 105 9-2 A priori confidence in validity of study findings, 106 9-3 Prematched herpes zoster vaccinated and unvaccinated cohorts, 108 9-4 Postmatched herpes zoster vaccinated and unvaccinated cohorts, 109 P REP UBLI CATI ON COP Y: UNCORR ECTED P ROOFS

BOXES, FIGURES, AND TABLES XV 9-5 Decision aid on questions to consider to assess and minimize bias in non-randomized observational comparisons, 112 10-1 Acceptability of real-world evidence (RWE) across Europe, 121 10-2 MonARC Bionetworks Integrated Learning Platform, 124 10-3 Hypothetical example of traditional design versus Bayesian adaptive design, 126 10-4 Standard separate trials for drugs A and B, 126 10-5 Combined platform trial for drugs A and B, 126 10-6 Hypothetical examples of cost savings, 127 10-7 Use of real-world data in evaluation of drugs for rare diseases, 130 TABLES 6-1 Real-World Endpoints in Six Datasets, 59 6-2 Correlation Between Real-World Overall Survival and Real-World Extracted Endpoints, 60 6-3 Patient-Generated Health Data for a Study of Multiple Sclerosis (MS), 70 7-1 Considerations for Study Design Restrictions, 81 P REP UBLI CATI ON COP Y: UNCORR ECTED P ROOFS

Acronyms and Abbreviations ACE angiotensin converting enzyme AE adverse event AFib atrial fibrillation aNSCLC advanced non-small cell lung cancer ARIA Active Risk Identification and Analysis ARISTOTLE Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation BEST Biologics Effectiveness and Safety BLA biologics license application Cal INDEX California Integrated Data Exchange CBER Center for Biologics Evaluation and Research CDER Center for Drug Evaluation and Research CDRH Center for Devices and Radiological Health CE European conformity CIOMS Council for International Organizations of Medical Sciences COPD Chronic Obstructive Pulmonary Disorder CPT Current Procedural Terminology CRISP Chesapeake Regional Information System for our Patients CSR Clinical Study Report CTTI Clinical Trials Transformation Initiative EHR electronic health record EMA European Medicines Agency ENGAGE AF-TIMI 48 Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation Thrombolysis in Myocardial Infarction 48 FDA U.S. Food and Drug Administration GCP good clinical practice P REP UBLI CATI ON COP Y: UNCORR ECTED P ROOFS xvii

XVIII EXAMINING THE IMPACT OF RWE ON MEDICAL PRODUCT DEVELOPMENT GSK GlaxoSmithKline ICD International Statistical Classification of Diseases and Related Health Problems ICH International Committee on Harmonisation IMDRF International Medical Device Regulators Forum IMI Innovative Medicines Initiative INR international normalized ratio InterSePT International Suicide Prevention Trial INVESTED INfluenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated heart failure IRB Internal Review Board JHHS Johns Hopkins Health System KP Kaiser Permanente MAPPs Medicines Adaptive Pathways to Patients MDEpiNet Medical Device Epidemiology Network MI myocardial infarction NEST National Evaluation System for health Technology NESTcc NEST Coordinating Center NHS National Health Service NICE National Institute for Health and Care Excellence (United Kingdom) NOAC novel oral anticoagulant NSAID non-steroidal anti-inflammatory drug OAC oral anticoagulant OHDSI Observational Health Data Sciences and Informatics OS overall survival PCORnet National Patient-Centered Clinical Research Network PEER Platform for Engaging Everyone Responsibly PFS progression-free survival PGHD patient-generated health data PMA premarket approval PPRN Patient-Powered Research Network PRO patient-reported outcome PROTECT Pharmacoepidemiological Research Outcomes of Therapeutics by European Consortium PTSD posttraumatic stress disorder PXE pseudoxanthoma elasticum RCT randomized controlled trial RE-LY Randomized Evaluation of Long-term Anticoagulation Therapy P REP UBLI CATI ON COP Y: UNCORR ECTED P ROOFS

ACRONYMS AND ABBREVIATIONS XIX ROCKET AF Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation RWD real-world data RWE real-world evidence SOC standard of care SOP standard operating procedure SSRI selective serotonin reuptake inhibitor TAVR transcatheter aortic valve replacement TTNT time to next treatment TTP time to progression TTTD time to treatment discontinuation VA U.S. Department of Veterans Affairs P REP UBLI CATI ON COP Y: UNCORR ECTED P ROOFS

Next: 1 Introduction »
Examining the Impact of Real-World Evidence on Medical Product Development: Proceedings of a Workshop Series Get This Book
×
Buy Paperback | $60.00
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

Randomized controlled trials (RCTs) have traditionally served as the gold standard for generating evidence about medical interventions. However, RCTs have inherent limitations and may not reflect the use of medical products in the real world. Additionally, RCTs are expensive, time consuming, and cannot answer all questions about a product or intervention. Evidence generated from real-world use, such as real-world evidence (RWE) may provide valuable information, alongside RCTs, to inform medical product decision making.

To explore the potential for using RWE in medical product decision making, the National Academies of Sciences, Engineering, and Medicine planned a three-part workshop series. The series was designed to examine the current system of evidence generation and its limitations, to identify when and why RWE may be an appropriate type of evidence on which to base decisions, to learn from successful initiatives that have incorporated RWE, and to describe barriers that prevent RWE from being used to its full potential. This publication summarizes the discussions from the entire workshop series.

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  6. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  7. ×

    View our suggested citation for this chapter.

    « Back Next »
  8. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!