Real-World Evidence Generation
and Evaluation of Therapeutics

PROCEEDINGS OF A WORKSHOP

Autumn Downey, Amanda Wagner Gee, and Anne B. Claiborne,
Rapporteurs

Forum on Drug Discovery, Development, and Translation

Board on Health Sciences Policy

Health and Medicine Division

THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu

THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001

This activity was supported by AbbVie Inc.; American Diabetes Association; American Society of Microbiology; Amgen Inc. (Contract No. GHCCOPS-CSARF-85167); Association of American Medical Colleges; AstraZeneca; Baxalta; Burroughs Wellcome Fund (Contract No. 1016598); Critical Path Institute; Eli Lilly & Co.; FasterCures; Friends of Cancer Research; GlaxoSmithKline (Contract No. 016084); Johnson & Johnson; Merck & Co., Inc. (Contract No. CMO-16208-001245); National Institutes of Health (NIH) (Contract No. HHSN263201200074I, Task Order 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; New England Journal of Medicine; Pfizer Inc.; Sanofi; Takeda Pharmaceuticals (Contract No. 53108); and U.S. Food and Drug Administration (Contract No. 1R13FD005496-01). 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: 978-0-309-45562-6
International Standard Book Number-10: 0-309-45562-6
Digital Object Identifier: https://doi.org/10.17226/24685

Additional copies of this publication are available for sale 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 2017 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. 2017. Real-world evidence generation and evaluation of therapeutics: Proceedings of a workshop. Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/24685.

PLANNING COMMITTEE ON REAL-WORLD EVIDENCE GENERATION AND EVALUATION OF THERAPEUTICS: A WORKSHOP¹

STEVEN K. GALSON (Co-Chair), Amgen Inc., Thousand Oaks, CA

GREGORY E. SIMON (Co-Chair), Group Health Research Institute, Seattle, WA

JESSE A. BERLIN, Johnson & Johnson, New Brunswick, NJ

LAURA M. DEMBER, University of Pennsylvania, Philadelphia

JOHN B. HERNANDEZ, Verily Life Sciences, San Francisco, CA

JOHN J. ORLOFF, Novelion Therapeutics, Cambridge, MA

BRAY PATRICK-LAKE, Duke Clinical and Translational Science Institute, Durham, NC

WILLIAM Z. POTTER, National Institute of Mental Health, Bethesda, MD

RHONDA J. ROBINSON BEALE, Blue Cross of Idaho, Meridian

NIGAM H. SHAH, Stanford University, CA

RACHEL E. SHERMAN, U.S. Food and Drug Administration, Silver Spring, MD

BRIAN L. STROM, Rutgers, State University of New Jersey, New Brunswick

Health and Medicine Division Staff

ANNE B. CLAIBORNE, Forum Director

AMANDA WAGNER GEE, Program Officer

REBECCA A. ENGLISH, Program Officer

MORGAN L. BONAME, Associate Program Officer

OLIVIA C. YOST, Senior Program Assistant

ANDREW M. POPE, Director, Board on Health Sciences Policy

___________________

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 rests with the workshop rapporteurs and the institution.

This page intentionally left blank.

FORUM ON DRUG DISCOVERY, DEVELOPMENT, AND TRANSLATION¹

RUSS ALTMAN (Co-Chair), Stanford University, CA

STEVEN GALSON (Co-Chair), Amgen Inc., Thousand Oaks, CA

MARGARET ANDERSON, FasterCures, Washington, DC

HUGH AUCHINCLOSS, National Institute of Allergy and Infectious Diseases, Bethesda, MD

CHRISTOPHER AUSTIN, National Center for Advancing Translational Sciences, Bethesda, MD

LINDA BRADY, National Institute of Mental Health, Bethesda, MD

GAIL CASSELL, Harvard Medical School Department of Social and Global Medicine (Visiting), Carmel, IN

ANDREW DAHLEM, Eli Lilly & Co., Indianapolis, IN

JAMES DOROSHOW, National Cancer Institute, Bethesda, MD

JEFFREY DRAZEN, New England Journal of Medicine, Boston, MA

JULIE GERBERDING, Merck & Co., Inc., Kenilworth, NJ (as of February 2017)

JODIE GILLON, Achillion Pharmaceuticals, New Haven, CT

LYNN HUDSON, Critical Path Institute, Tucson, AZ

S. CLAIBORNE JOHNSTON, Dell Medical School, The University of Texas at Austin

GREGORY KEENAN, AstraZeneca, Summit, NJ (as of February 2017)

RUSTY KELLEY, Burroughs Wellcome Fund, Research Triangle Park, NC

KATE KNOBIL, GlaxoSmithKline, Collegeville, PA

FREDA LEWIS-HALL, Pfizer Inc., New York, NY

ROSS McKINNEY, Association of American Medical Colleges, Washington, DC (as of September 2016)

BERNARD MUNOS, FasterCures, Washington, DC

JOHN ORLOFF, Novelion Therapeutics, Cambridge, MA

ROBERT RATNER, American Diabetes Association, Alexandria, VA (until January 2017)

MICHAEL ROSENBLATT, Merck & Co., Inc., Kenilworth, NJ

MICHAEL SEVERINO, AbbVie Inc., North Chicago, IL

RACHEL SHERMAN, U.S. Food and Drug Administration, Silver Spring, MD

ELLEN SIGAL, Friends of Cancer Research, Washington, DC

LANA SKIRBOLL, Sanofi, Washington, DC

BRIAN STROM, Rutgers, State University of New Jersey, Newark

___________________

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 rests with the workshop rapporteurs and the institution.

JOHN WAGNER, Takeda Pharmaceuticals, Cambridge, MA

JOANNE WALDSTREICHER, Johnson & Johnson, New Brunswick, NJ

ALAN WILLARD, National Institute of Neurological Disorders and Stroke, Bethesda, MD

CARRIE WOLINETZ, National Institutes of Health, Bethesda, MD

JANET WOODCOCK, U.S. Food and Drug Administration, Silver Spring, MD

Health and Medicine Division Staff

ANNE B. CLAIBORNE, Forum Director

REBECCA A. ENGLISH, Program Officer

AMANDA WAGNER GEE, Program Officer

MORGAN L. BONAME, Associate Program Officer

OLIVIA C. YOST, Senior Program Assistant

ANDREW M. POPE, Director, Board on Health Sciences Policy

Reviewers

This Proceedings of a Workshop 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:

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 Daniel R. Masys, University of Washington. He was 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.

This page intentionally left blank.

Contents

ACRONYMS AND ABBREVIATIONS

1 INTRODUCTION

Organization of the Proceedings of a Workshop

2 IMPROVING EVIDENCE GENERATION FOR DECISION MAKING ON APPROVAL AND USE OF NEW TREATMENTS: SOME STAKEHOLDER PRIORITIES

The Current Landscape for Evidence Generation Processes

Stakeholder Perspectives on Priorities for Improving Real-World Decision Making

Potential Crosscutting Priorities for Improving Real-World Decision Making

3 OPPORTUNITIES FOR REAL-WORLD DATA

Leveraging Electronic Health Records

The Power of Linking and Mining Disparate Data Sources

Collecting Real-World Data Outside the Clinical Setting Using Digital Health Tools

Considerations for Realizing the Potential of Real-World Data

4 GENERATING AND INCORPORATING REAL-WORLD EVIDENCE INTO MEDICAL PRODUCT DEVELOPMENT AND EVALUATION: BUILDING FROM SUCCESSFUL CASE STUDIES

Randomization in the Clinical Setting

Research Embedded in Registries

Population-Based Surveillance Using Health System Data

5 POTENTIAL STRATEGIES FOR A WAY FORWARD

Data Availability

Study Design, Data Methods, and Data Quality

Incentives

Some Practical Next Steps

APPENDIXES

A Bibliography

B Workshop Agenda

C Participant Biographies

D Discussion Paper: Real-World Evidence to Guide the Approval and Use of New Treatments

Boxes and Figures

BOXES

1-1 Statement of Task

1-2 Potential Additional Uses of Real-World Evidence as Outlined by Individual Speakers

2-1 A Call to Action

4-1 Knowledge Generation with EHR Data at VA

4-2 Critical Elements in the Success of the Sentinel Initiative

5-1 Federal Systems and Initiatives Related to Evidence Generation

FIGURES

1-1 Examples of current uses of real-world evidence derived from diverse and complex sources.

3-1 Optum’s process for aggregating data from multiple provider networks into a centralized data repository.

4-1 A model for a tiered national device registry infrastructure.

4-2 Schema for leveraging OHDSI resources to inform patient care decisions and clinical studies.

This page intentionally left blank.

Acronyms and Abbreviations