MEDICATIONS IN
SINGLE-DOSE VIALS

Implications of Discarded Drugs

Edward H. Shortliffe, Francis K. Amankwah,
Tracy A. Lustig, and Sharyl J. Nass, Editors

Committee on Implications of Discarded Weight-Based Drugs

Board on Health Care Services

Health and Medicine Division

A Consensus Study Report of

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

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This activity was supported by an agreement between the National Academy of Sciences and Centers for Medicare & Medicaid Services, U.S. Department of Health and Human Services. 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: 978-0-309-68207-7
International Standard Book Number-10: 0-309-68207-X
Digital Object Identifier: https://doi.org/10.17226/25911
Library of Congress Control Number: 2021932057

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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2021. Medications in single-dose vials: Implications of discarded drugs. Washington, DC: The National Academies Press. https://doi.org/10.17226/25911.

COMMITTEE ON IMPLICATIONS OF DISCARDED WEIGHT-BASED DRUGS

EDWARD SHORTLIFFE (Chair), Chair Emeritus and Adjunct Professor of Biomedical Informatics, Columbia University; Adjunct Professor of Biomedical Informatics, Arizona State University; Adjunct Professor of Population Health Sciences, Weill Cornell Medical College

JULIE DONOHUE, Professor of Health Policy and Management, University of Pittsburgh

ANUPAM JENA, Associate Professor of Health Care Policy and Medicine, Harvard Medical School; Assistant Physician, Massachusetts General Hospital

TRACY LIEU, Director, Division of Research, Kaiser Permanente Northern California

GARY LYMAN, Professor of Medicine, University of Washington School of Medicine; Professor, Divisions of Public Health Sciences and Clinical Research, Fred Hutchinson Cancer Research Center

KAVITA PATEL, Fellow, The Brookings Institution

HAROLD PAZ, Executive Vice President and Chancellor for Health Affairs, The Ohio State University, Chief Executive Officer, Ohio State University Wexner Medical Center

DEBORAH SCHRAG, Chief, Division of Population Sciences, Medical Oncology, Dana-Farber Cancer Institute; Professor of Medicine, Harvard Medical School

YA CHEN TINA SHIH, Professor of Health Economics, Department of Health Services Research, The University of Texas MD Anderson Cancer Center

KENNETH SILVERMAN, Director of Packaging Technology, Global Technical Operations, AstraZeneca

HOLLY TAYLOR, Research Bioethicist, Department of Bioethics, Clinical Center, National Institutes of Health

JONATHAN WATANABE, Professor of Clinical Pharmacy and Associate Dean of Assessment and Quality, University of California, Irvine, School of Pharmacy and Pharmaceutical Sciences

ALASTAIR WOOD, Emeritus Professor of Medicine and Pharmacology, Vanderbilt University

K. ROBIN YABROFF, Senior Scientific Director, American Cancer Society

NOTE: See Appendix E, Disclosure of Unavoidable Conflicts of Interest.

Study Staff

FRANCIS KWADWO AMANKWAH, Study Director

ALEXANDRA ANDRADA, Associate Program Officer

ANNALEE GONZALES, Administrative Assistant

TRACY A. LUSTIG, Senior Program Officer

MICAH WINOGRAD, Financial Officer

ANNE MARIE HOUPPERT, Senior Librarian

SHARYL J. NASS, Senior Director, Board on Health Care Services

Consultants

ADITI P. SEN, Johns Hopkins Bloomberg School of Public Health

HUI ZHAO, The University of Texas MD Anderson Cancer Center

Editorial Consultant

ROBERT POOL

Reviewers

This Consensus Study Report 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 report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process.

We thank the following individuals for their review of this report:

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report, nor did they see the final draft before its release. The review of this report was overseen by ROBERT D. REISCHAUER, Urban Institute, and BRADFORD H. GRAY, Urban Institute. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.

Acknowledgments

The study committee and the Health and Medicine Division (HMD) project staff take this opportunity to recognize and thank the many individuals who shared their time and expertise to support the committee’s work and to inform deliberations.

This study was supported by Funding Opportunity Number CMS-2E2-19-001 from the Centers for Medicare & Medicaid Services, U.S. Department of Health and Human Services (HHS). The contents provided do not necessarily represent the official views of HHS or any of its agencies.

The committee benefited greatly from discussions with individuals who made presentations during the committee’s open sessions and participated in the discussions: Corinne Axelrod, Peter Bach, Alexander Bastian, Corbin Bennett, Donald M. Berwick, Amitabh Chandra, Jacqueline Corrigan-Curay, Francis Crosson, Gwen Darien, Stacey Dusetzina, Michael Ganio, Peter Gilbar, Sherry Glied, Kedar Gokhale, Daniel Goldstein, Mireille Jacobson, Ronald Khoury, Prabath Malluwa-Wadu, Richard L. Schilsky, Michael Seiden, Brian Serumaga, and Sarah Shirey-Losso. The committee is very grateful to these presenters for volunteering to share their knowledge, data, and expert opinions with the committee and members of the public who attended the committee’s open sessions.

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Contents

PREFACE

SUMMARY

1 INTRODUCTION

Study Charge

Committee’s Approach

Context of Rising Health Care Costs

Question of Waste

Structure of the Report

References

2 SINGLE-DOSE VIALS OF WEIGHT-BASED DRUGS

Drug Discovery and Development Process

Drug Dosing

Vial Sizes

Guidance from Federal and Nongovernmental Organizations

Clinician Acquisition of and Payment for Drugs

Patient Quality of Care

Key Findings

Conclusions

Recommendations

References

3 SCOPE OF DISCARDED DRUGS FROM SINGLE-DOSE VIALS

Analysis of Medicare Spending on Discarded Drugs

Analysis of Private Payers’ Spending on Discarded Drugs

Limitations

Key Findings

Conclusions

Recommendation

References

4 EFFORTS TO REDUCE DISCARDED WEIGHT-BASED DRUGS

U.S. Congress

Professional Organizations

Clinical Practices

U.S. Department of Health and Human Services Partnerships with Federal and Nonfederal Partners

Integrated Health Care Delivery Systems, Traditional Fee-for-Service Systems, and the Underserved

Key Findings

Conclusions

Recommendations

References

5 DISCARDED WEIGHT-BASED DRUGS IN SINGLE-DOSE VIALS

Why Are Drugs So Expensive?

Approaches to Managing Drug Costs

Economics of Packaging Weight-Based Drugs

Value of Unused Single-Dose Vial Drugs

Role of Reimbursement in Shaping Attitudes Toward Discarded Drugs

Likely Unintended Consequences of Efforts to Reduce Discarded Drugs

Key Findings

Conclusions

Recommendation

References

6 PRESCRIPTION FOR REDUCING DISCARDED DRUGS

Goals and Recommendations

Interdependencies of Recommendations

A Pivotal Time for Action

APPENDIXES

A GLOSSARY

B SUPPLEMENTAL FIGURES AND TABLES FROM COMMISSIONED ANALYSES

C STAKEHOLDER INPUT

D BIOGRAPHICAL INFORMATION

E DISCLOSURE OF UNAVOIDABLE CONFLICTS OF INTEREST

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Preface

As a physician in training—and later as a practicing clinician—I can remember well some puzzlement when I observed (or personally performed) a treatment that involved breaking the top off a glass vial (or piercing the rubber cap) and extracting a medication from the vial into a syringe. The subsequent infusion into a vein, or injection into a muscle or under the skin, was of course the primary focus of the activity, but the puzzlement arose because often the entire vial was not required for the dose of treatment that the patient was to receive. I would notice the remaining liquid in the bottom of the vial and realize that many questions arose about the process. What should happen with the remaining liquid? Could I save it for another patient? Under what conditions? If not, how should it be safely discarded? Could I have simply administered the entire vial in order to avoid leaving this excess? Did the remaining liquid have value? If so, who was paying for it? (The patient? The treating organization or clinician? The insurer? The pharmaceutical company?) Was the failure to use the entire vial a serious waste of resources?

I recall that we avoided simply dumping the excess liquid down the sink, but the disposal process was often haphazard, and the questions I considered at the time were seldom discussed. The bulk of the medication was generally administered to the patient, and there seemed to be little reason to be overly concerned about the typically small amount of extra liquid that was left behind in the vial. The vial was generally not too expensive, and there was little focus on the issue of waste.

In recent years, however, there has been an explosion in the use of specialty medications that are produced and distributed in vials—typically

chemotherapeutic agents or immunologics. Unlike the vials of the past, these individual vials are often extremely expensive, with prices in the thousands of dollars each. Since many of these medications are dosed based on the individual patient’s weight or body surface area, it is common for some medication to be left behind after the needed amount, which can vary significantly among patients, is withdrawn from a vial. Yet, concerns about sterility and environmentally correct preservation of the medications prevent the excess from being saved for future use, leading to its being discarded. Given the unit prices of such vials, it is natural to ask how much is being spent unnecessarily on the liquid treatment that is never actually administered to a patient.

Now that specialty drugs make up about 2 percent of total prescription volume but account for one-half of the overall cost of drugs for the U.S. health care system, it is natural for health insurers, including the Centers for Medicare & Medicaid Services (CMS), to ask whether they are spending more than they should on liquid medications that are delivered in glass vials and dosed based on a patient’s body size (weight or body surface area). Since some have estimated that the discarded medications may, on a prorated basis, be costing CMS billions of dollars annually, the question has also drawn the attention of the U.S. Congress. Congress accordingly mandated CMS to commission a study by the National Academies of Sciences, Engineering, and Medicine (the National Academies) to address the question of how the nation might best address the perceived failure of the health system to handle effectively and efficiently the weight-based dosing of medications in glass vials. The Committee on Implications of Discarded Weight-Based Drugs was formed in response to this request from CMS.

As we investigated the issues relevant to this topic, the committee members learned quickly that what at first appeared to be a simple question about vials was actually opening up a complex and varied set of related topics. These topics begin with the development of new drugs, carry through clinical trials and the regulatory process, and inevitably involve not only payers for the medications but also the pharmaceutical manufacturers, intermediaries involved with the storage and distribution requirements for the relevant medications, the purchasers and their clinical practices, and ultimately the administration of treatment. Even the concept of “waste” in this context became a matter for debate and clarification, relating to economic concepts of value and how pricing is determined. Also important were patterns of reimbursement, the role of Medicare Part B (rather than Part D) in the coverage for the most expensive specialty medications, and the implications of unused medications from the perspectives of patients—especially if they lacked comprehensive supplemental (MediGap) insurance under Part B.

I should also mention the importance to the committee of an earlier (2018) National Academies report, Making Medicines Affordable: A National Imperative. We found the conclusions and recommendations in that report to be both compelling and highly relevant to our own deliberations. Our committee’s recommendations can be viewed as building on insightful work that went before, as is emphasized in this report itself.

The committee was challenged by unexpected and complicated issues that arose as the National Academies’ typical study processes encountered the 2020 coronavirus disease 2019 (COVID-19) pandemic. Although we were able to meet face to face in January 2020 for our first meeting and had the pleasure of getting to know one another individually at that time, the remaining meetings, workshops, and report deliberations were all held online. We held virtual public hearings via video telecommunication connections on several occasions, receiving briefings that greatly informed the content of the report and our ultimate conclusions and recommendations.

The release of COVID-19 vaccines in December 2020 offered us confirmatory evidence regarding the problem we were studying and, in particular, the advantages of multi-dose vials. Our last committee meeting, included some discussion (and a few moments of levity) as members commented on the sudden public awareness of the advantages of multi-dose vials. A sixth dose of vaccine was discovered in vials that were meant to include only five doses, thereby allowing one more individual to be vaccinated from each vial. Accordingly, there was elation in the public health community and major news coverage of an issue that readers will find addressed within the pages of this report.

Despite the pandemic that forced us into unusual virtual meeting conditions, we had vibrant discussions and built close collaborative relationships, both among the committee members and with the remarkable staff from the National Academies’ Health and Medicine Division who guided us through the process. The National Academies deserve recognition and credit for the way in which they responded to the demand for a technological solution to the requirements of our committee as well as many other National Academies activities that have occurred in 2020.

We accordingly begin our thanks with recognition of our study director, Francis Amankwah, whose energy and commitment to the project were evident throughout. He had an excellent grasp of the issues (having worked on the earlier Making Medicines Affordable report), organized our efforts with great skill, and demonstrated an ability to capture in writing what committee members discussed or submitted for inclusion. Assisted by Alexandra Andrada (associate program officer) and Annalee Gonzales (administrative assistant), the team mastered the technology and impressed us all with their skill and camaraderie. We note as well

the important oversight roles played by Tracy Lustig (senior program officer) and Sharyl Nass (who directs the Board on Health Care Services at the National Academies), both of whom regularly attended our virtual meetings. We benefited greatly from their wisdom and experience.

The committee (see Appendix D) thanks the many individuals who provided briefings on key topics that we needed to understand or who submitted written comments that informed our deliberations (see Appendix C). We found that much of what we needed to study was not previously well documented in writing, so the testimony of these key individuals was valuable and highly appreciated. The detail provided in the report is largely derived from the information provided by these experts and stakeholders.

Some of the information we needed required additional data analysis, and we are grateful for extensive work performed on the committee’s behalf by Aditi Sen (Johns Hopkins Bloomberg School of Public Health) and Hui Zhao (The University of Texas MD Anderson Cancer Center). Much of the discussion in Chapter 3 (and in Appendix B) would not have been possible without their rigorous assessment of the relevant Medicare and IBM MarketScan data that were available to us.

As committee chair I want to express also my sincere thanks to the committee members themselves. It was a wonderful group with whom to work, beautifully balanced with regard to expertise and with a uniform commitment to fulfilling the task at hand—even with the complications introduced into the normal study process by the pandemic. Some of the clinicians on the committee had to excuse themselves for periods of times during a call when they had to address the clinical needs of a coronavirus patient, but they returned to re-immerse themselves quickly in the ongoing discussions. I am grateful for having had the opportunity to work with this superb group of scientists and clinicians.

Edward Shortliffe, Chair
Committee on Implications of Discarded Weight-Based Drugs