A Review of Selected Federal Vaccine and Immunization Policies, Based on Case Studies of Pneumococcal Vaccine September 1979 NTIS order #PB80-116106 Library of Congress Catalog Card Number 79-600165 For sale by the Superintendent of Documents, U.S. Government Printing Office Washington, D.C. 20402 Stock No. 052-003 -00701-1 — FOREWORD This work originated in April 1978 as a background study in OTA’S Congressional Fellowship Program. The study initially was limited to an analysis of the benefits and costs of pneumococcal vaccine, with particular emphasis on vaccine reimbursement under Medicare for the elderly. As a result of encouragement by several reviewers, the scope of investigation was broadened substantially to include three other areas of vaccine policy concerns: research, development, and production; safety and efficacy; and 1iabili- ty. Cost-effectiveness analysis was selected to assess benefits and costs, and the entire report was incorporated into a larger OTA study entitled Cost-Effectiveness of Medical Technologies. This report is the first of six documents to be published as a part of the larger cost-effectiveness study. A Review of Selected Federal Vaccine and Immunnization Policies was prepared by OTA staff in consultation with several authorities in the relevant subject areas. The authors’ professional backgrounds include training in pubic health, pharmacy, econom- ics, law, medicine, public administration, public policy, and political science. Consult- ants included representatives from pharmaceutical companies, including Eli Lilly and Company, Merck Sharp and Dohme, and Lederle Laboratories; Government agencies, including the Bureau of Biologics (BOB), Center for Disease Control (CDC), National In- stitute of Allergy and Infectious Diseases (NIAID), National Center for Health Statistics (NCHS), and Bureau of the Census; and academic institutions, in particular, Duke Uni- versity, Harvard University, the University of Pennsylvania, and the University of Cali- fornia at San Francisco. Drafts of the report were reviewed by members of two OTA advisory bodies: the Health Program Advisory Committee and the Cost-Effectiveness of Medical Technol- ogies Advisory Panel. Various drafts also were reviewed by approximately so other indi- viduals representing a wide range of professional disciplines. We were grateful for these many contributions to the work. ~ JOHN H. GIBBONS Director iii * OTA HEALTH GROUP STAFF Joyce C. Lashof, Assistant Director Health and Life Sciences Division H. David Banta, Health Group Manager Michael A. Riddiough, Project Director Jane Sisk Willems, Health Econonmics and Policy Co-Project Director (April-September 1978) Claudia Sanders, Health Policy Lawrence Miike, Vaccine Liability John Bell, Computer Modeling Clyde Behney, Health Policy Editorial Staff Kerry B. Kemp, Editor and Writer’ Page S. Gardner, Editor Administrative Staff Virginia Cwal ina Shirley Ann Gayheart William S. Burnett OTA PUBLISHING STAFF John C. Holmes, Publishing Officer Kathie S. Boss Joanne Heming + Independent cc)ntrac I(,r OTA HEALTH GROUP ADVISORY COMMITTEE Frederick C. Robbins, Chairman Dean, School of Medicine, Case Western Reserve University Stuart H. Altman Sidney S. Lee Dean Associate Dean Floremce Heller School Community Medicine Brandeis University McGill Unversity Robert M. Ball Mark Lepper Senior Scholar Vice President for Evaluation Institute of Medicine Rush-Presbyterian Medical School National Academy of Sciences St. Luke’s Medical Center Bernard Barber Professor C. Frederick Mosteller Professor and Chairman Department of Sociology Barnard College Department of Biostatistics Columbia University School of Public Health Harvard University Lewis H. Butler Adjunct Professor of Health Policy Beverlee Myers Health Policy Program Director University of California Department of Health Services State of California Kurt Deuschle Professor of Community Medicine Helen Ewing Nelson Mount Sinai School of Medicine President Consumer Research Foundation Rashi Fein Mill Valley, Calif. Professor of tile Economics of Medicine Center for Comunity Health and Medical Care Charles A. Sanders General Director Harzard Medical School Massachusetts General Hospital Melvin A. Glasser Director Kerr L. White Social Security Department Deputy Director of Health Sciences United Auto Workers Rockefeller Foudation COST-EFFECTIVENESS OF MEDICAL TECHNOLOGIES ADVISORY PANEL MEMBERS John R. Hogness, Chairman President, Association for Academic Health Centers Sheldon Leonard Mnager Regulatory Affairs General Electric Company Barbara J. McNeil Department of Radiology Peter Bent Brigham Hospital Robert H. Moser Executive Vice President American College of Physicians C. Frederick Mosteller Chirman Department of Biostatistics Harward University Robert M. Sigmond Advisor in Hospital Affairs Blue Cross and Blue Shield Associates Jane Sisk Willems V.A. Scholar Veterans Administration vii — ACKNOWLEDGMENTS Several people provided valuable assistance in the preparation of this report. Indi- viduals at the National Center for Health Statistics (NCHS), in particular, were very in- strumental in developing data sets for the cost-effectiveness analysis. While OTA must assume ultimate responsibility for the content of this report, it greatly appreciates the contributions of—among many others—the following individuals: Clarence A. Abramson Alan R. Hinman, M. D., M.P.H. Paul D. Parkman, M.D. Senior Counsel Center for Disease Control Deputy Director Merck and Company, Inc. Atlanta, Ga. Bureau of Biologics Rahway, N.J. Food and Drug Administration Robert Austrian, M.D. Mark Hornbrook, Ph.D. Bethesda, Md. Department of Research Medicine National Center for Health University of Pennsylvania Services Research Frederick C, Robbins, M.D. School of Medicine Hyattsville, Md. Dean, School of Medicine Philadelphia, Pa. Irving S. Johnson, Ph.D. Case Western Reserve University Michael Beatrice, R. Ph., M.S. Vice President of Research Cleveland, Ohio Bureau of Biologics Eli Lilly and Company Food and Drug Administration Indianapolis, Ind. John Robbins, M.D. Bethesda, Md. Bureau of Biologics Joel Kavet, D. SC. Claire Broome, M.D. Food and Drug Administration Department of Health, Education, Center for Disease Control Bethesda, Md. and Welfare Atlanta, Ga. Rockville, Md. David W. Fraser, M. D., Donald Shepard, Ph.D. Center for Disease Control Kenneth Manton, Ph.D. Harvard School of Public Health Atlanta, Ga. Duke University Boston, Mass. Donald Hill Durham, N.C, Bureau of Biologics Eric Stollard Food and Drug Administration Barbara J. McNeil, M. D., Ph.D. Duke University Bethesda, Md. Harvard Medical School Durham, N.C. Boston, Mass. James Hill, Ph.D. Judith Wagner, Ph.D. National Institute of Allergy and Harry M. Meyer, Jr., M.D. Infectious Diseases Director Urban Institute Washington, D.C. Bethesda, Md. Bureau of Biologics Maurice Hilleman, Ph. D., D. SC. Food and Drug Administration Director Bethesda, Md. Ronald Wilson Merck Institute for National Center for Health Statistics Elena Nightingale, M.D. Department of Health, Education, Therapeutic Research Institute of Medicine and Welfare West Point, Pa. Washington, D.C. Hyattsville, Md. CONTENTS Page . Glossary of Terms . Xlll Glossary of Acronyms. xvi chapter 1. SUMMARY . 3 Introduction . ., . 3 Vaccine Research, Development, and Production . 4 Vaccine Safety and Efficacy. 7 Cost-Effectiveness Analysis of Vaccination Programs . 10 General Applications of CEA . 10 CEA and Its Relationship to Reimbursement for Vaccinations . 11 CEA Methodology and Data . 12 Legal Liability and Compensation for Vaccine-Related Injuries ., . 13 Scope of the Study. 16 Organization of the Report . ., . 17 2. A CASE STUDY: FINANCING THE RESEARCH AND DEVELOPMENT OF PNEUMOCOCCAL VACCINE . 23 Background and Introduction . , . 23 Early Pneumococcal Vaccine Research and Development (1881-1966) . 32 Federal Government Participation in the Research and Development of Pneumococ- cal Vaccine (1967-79). 33 Industry Participation in the Research and Development of Pneumococcal Vaccine (1967-79) . 34 The Role of Federal Financing in the Research and Development of Pneumococcal Vaccine . 36 3. A CASE STUDY: EVALUATING THE SAFETY AND EFFICACY OF PNEUMOCOCCAL VACCINE . 41 Background and Introduction . 41 Types of Studies Used To Evaluate the Safety and Efficacy of Polyva Pneumococcal -. Vaccine . 43 Results of Premarketing Clinical Trials of Pneumococcal Vaccine . 47 Clinical Safety . 47 Clinical Efficacy . 49 BOB’s Prelicensing Evaluation of Pneumococcal Vaccine. 51 Postmarketing Data Regarding the Safety and Efficacy of Pneumococcal Vaccine . 52 Limitations of Premarketing Evaluations of the Safety and Efficacy of Pneumococcal Vaccine . 56 Inherent Limitations of Premarketing Clinical Studies . 56 Vaccine Testing Among Foreign Populations . 57 Lack of Vaccine Testing Among High Risk Populations . 60 4. A CASE STUDY: COST-EFFECTIVENESS ANALYSIS OF VACCINATION AGAINST PNEUMOCOCCAL pneumonia . 65 Background and Introduction . 65 ix — CONTENTS—continued Page Measurement of Health Effects and Societal Medical Costs of Pneumococcal Vaccination . 66 Health Effects . 67 Medical Care Costs. 68 Cost-EffectivenessEquationand Model . 68 Base Case and Sensitivity Analysis. 69 Data Sources . 70 Results . 71 Base Case . 72 Sensitivity Analysis. 73 Modification of the Model for the High Risk Population . 76 Modification of the Societal Model for Medicare . 77 Discussion of Results . 78 5. A REVIEW: LEGAL LIABILITY AND COMPENSATION FOR VACCINE-RELATED INJURIES. 83 Background and Introduction . 83 Case Law onVaccine-Related Injuries . 87 Legal Determination of Liability by Courts of Different Jurisdictions . 87 Causes of Action for Vaccine-Related Injuries . 88 Legal LiabilityTheories Embodied in Recent Case Law . 89 Principles Underlying Pricing of Liability Insurance. 92 Coverage . 93 Ratemaking . 95 Vaccine Risks, Adverse Reactions, and Liability Claims. ..