Cover Image

PAPERBACK
$43.50



View/Hide Left Panel

New Vaccine Development Establishing Priorities

VOLUME II Diseases of Importance in Developing Countries

Part Two of a Two-Part Study by the

Committee on Issues and Priorities for New Vaccine Development

Division of Health Promotion and Disease Prevention and Division of International Health

INSTITUTE OF MEDICINE

NATIONAL ACADEMIES PRESS

Washington, D.C.
1986
www.nap.edu



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page R1
Survey New Vaccine Development Establishing Priorities VOLUME II Diseases of Importance in Developing Countries Part Two of a Two-Part Study by the Committee on Issues and Priorities for New Vaccine Development Division of Health Promotion and Disease Prevention and Division of International Health INSTITUTE OF MEDICINE NATIONAL ACADEMIES PRESS Washington, D.C. 1986 www.nap.edu

OCR for page R1
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries NATIONAL ACADEMY PRESS 2101 CONSTITUTION AVE., NW WASHINGTON, DC 20418 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The Institute of Medicine was chartered in 1970 by the National Academy of Sciences to enlist distinguished members of the appropriate professions in the examination of policy matters pertaining to the health of the public. In this, the Institute acts under both the Academy’s 1863 congressional charter responsibility to be an adviser to the federal government and its own initiative in identifying issues of medical care, research, and education. The work on which this publication is based was initiated and funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, under contract No. NO1-AI-22678. The U.S. Agency for International Development, through the Public Health Service’s Vaccine Development and Health Research Participating Agency Services Agreement No. 000001-04-S5, also provided valuable financial support. Library of Congress Cataloging-in-Publication Data (Revised for vol. 2) New vaccine development. Prepared for the National Institute of Allergy and Infectious Diseases. Includes bibliographies and index. Contents: v. 1. Diseases of importance in the United States—v. 2. Diseases of importance in developing countries. 1. Vaccines—Research—Government policy. 2. Communicable diseases—United States—Preventive inoculation. 3. Communicable diseases—Developing countries—Preventive inoculation. I. Institute of Medicine (U.S.). Committee on Issues and Priorities for New Vaccine Development. II. National Institute of Allergy and Infectious Diseases (U.S.) RA638.N49 1985 614.4’7’0973 84–62037 ISBN 0-309-03494-9 (pbk.: v. 1) ISBN 0-309-03679-8 (v. 2) Printed in the United States of America

OCR for page R1
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries Committee on Issues and Priorities for New Vaccine Development SAMUEL L.KATZ (chair), Department of Pediatrics, Duke University Medical Center A.JOHN BEALE, Wellcome Research Laboratories, United Kingdom MARSHALL H.BECKER, Department of Health Behavior and Health Education, University of Michigan, Ann Arbor JAMES CHIN, Department of Health Services, State of California Health and Welfare Agency, Berkeley PURNELL W.CHOPPIN, Howard Hughes Medical Institute, Bethesda, Md. THEODORE C.EICKHOFF, Department of Internal Medicine, Presbyterian/St Luke’s Medical Center, Denver FRANCIS A.ENNIS, Department of Medicine and Molecular Genetics, University of Massachusetts Medical Center, Worcester HARVEY V.FINEBERG, Institute for Health Research, Harvard School of Public Health MAURICE R.HILLEMAN, Merck Institute for Therapeutic Research, Merck Sharp & Dohme Research Laboratories GERALD T.KEUSCH, Division of Geographic Medicine, Tufts University RICHARD F.KINGHAM, Covington and Burling, Washington, D.C. BERNARD ROIZMAN, Department of Microbiology and Biophysics, University of Chicago HENRY R.SHINEFIELD, Department of Pediatrics, Kaiser Permanente Medical Group, San Francisco JANE E.SISK, Office of Technology Assessment, United States Congress CLADD E.STEVENS, Laboratory of Epidemiology, The New York Blood Center LEROY WALTERS, Kennedy Institute of Ethics, Georgetown University MILTON C.WEINSTEIN, Institute for Health Research, Harvard School of Public Health See Appendix G for further information on committee members. Institute of Medicine Staff ROY WIDDUS, Study Director and Director, Division of International Health ENRIQUETA C.BOND, Director, Division of Health Promotion and Disease Prevention GUTHRIE BIRKHEAD, Consultant CYNTHIA HOWE, Research Assistant ELAINE MCGARRAUGH, Staff Associate EVE K.NICHOLS, Editor JUDE C.PAYNE, Research Assistant GAIL E.SPEARS, Administrative Secretary NORA STEINER, Research Assistant

OCR for page R1
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries Consultants FAKHRY ASSAAD, Division of Communicable Diseases, World Health Organization, Geneva NATTH BHAMARAPRAVATI, Mahidol University, Thailand CHARLES C.J.CARPENTER, Department of Medicine, Case Western Reserve University FEDERICO CHAVEZ-PEON, Industria Paraestatal Farmaceutica, FISOMEX, Mexico SCOTT HALSTEAD, Health Sciences Division, The Rockefeller Foundation KARL M.JOHNSON, Hoffman-LaRoche, Incorporated ADETOKUNBO O.LUCAS, Special Programme for Research and Training in Tropical Diseases, World Health Organization ARNOLD S.MONTO, School of Public Health, University of Michigan FRANKLIN A.NEVA, National Institute of Allergy and Infectious Diseases, National Institutes of Health S.RAMACHANDRAN, Department of Science and Technology, Government of India JOHN B.ROBBINS, National Institute of Child Health and Human Development, National Institutes of Health JONAS SALK, The Salk Institute for Biological Studies DONALD S.SHEPARD, Institute for Health Research, Harvard School of Public Health DAVID H.SMITH, Department of Pediatrics, University of Rochester PHILIPPE STOECKEL, Association pour la Promotion de la Medicine Preventive, Paris JULIA WALSH, Harvard Medical School KENNETH WARREN, Health Sciences Division, The Rockefeller Foundation THOMAS H.WELLER, Department of Tropical Public Health, Harvard School of Public Health National Institute of Allergy and Infectious Diseases Steering Committee ROBERT M.CHANOCK, Chief, Laboratory of Infectious Diseases WILLIAM JORDAN, Director, Microbiology and Infectious Diseases Program JOHN E.NUTTER, Chief, Office of Program Planning and Evaluation BERNARD TALBOT, Deputy Director, National Institute of Allergy and Infectious Diseases C.DAVID WISE, Chief, Evaluation Section, Office of Program Planning and Evaluation U.S. Agency for International Development Advisors GEORGE T.CURLIN, Assistant Director for Health Research, Office of International Health, Public Health Service KENNETH J.BART, Director, Office of Health, U.S. Agency for International Development Liaison Committee BENNETT ELISBERG, Director, Division of Product Quality Control, Food and Drug Administration ALAN HINMAN, Director, Division of Immunization, Center for Prevention Services, Centers for Disease Control JEFFREY KOPLAN, Assistant Director for Public Health Practice, Centers for Disease Control PHILIP K.RUSSELL, Commander General, Fitzsimmons Army Medical Center

OCR for page R1
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries Acknowledgements This report could not have been prepared without the assistance of many individuals who willingly gave their valuable time to provide information and advice, and to prepare or comment on draft sections of the final document. A list of those to whom the committee is particularly indebted appears as Appendix H. It is possible that some individuals may have been omitted from this list by oversight. If this has happened, the committee offers its sincere apologies.

OCR for page R1
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries This page intentionally left blank.

OCR for page R1
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries Preface This volume is the second report from the Institute of Medicine’s Committee on Issues and Priorities for New Vaccine Development. The first report dealt with vaccines for diseases of importance in the United States. The purpose of this volume is to help in setting priorities for the accelerated development of vaccines against diseases prevalent in developing countries. The background of the study and the committee’s approach were outlined in the preface to Volume I, which is reprinted in Appendix J. The project was initiated by the National Institute of Allergy and Infectious Diseases, which provided major funding for the overall effort. For the second phase of the project on diseases of importance in developing countries, valuable financial support was also provided by the U.S. Agency for International Development. In the second phase of the study, the committee made particular efforts to draw on the expertise and opinions of individuals who have worked extensively in public health fields in developing countries. Consultants from several parts of the world attended a meeting of the committee in August 1984, and many others contributed views by mail or telephone. Any group assessing vaccine development—whether for disease afflicting the United States population or mankind in general—would be sorely remiss if it omitted consideration of acquired immune deficiency syndrome (AIDS). As the committee was completing its first analysis, reports identifying the probable etiologic agent of AIDS were emerging, scarcely three to four years after the recognition of the syndrome. At that time, the committee believed that comparison of AIDS vaccine prospects with those of other advanced candidates for accelerated vaccine development would have been premature. In the ensuing year remarkable progress has been made, largely because of the powerful molecular and cellular biotechnologies that have emerged from basic biomedical research. Yet, significant questions remain before the prospects for vaccine development can be assessed clearly or its priority relative to other diseases evaluated. Uncertainty and apprehension as to the increasing magnitude of the problem (both domestic and global) is but one reason why this disease may merit separate consideration. The state of knowledge in this area is now approaching that where consideration can be given to the question of accelerated AIDS vaccine development. However, the Committee on Issues and Priorities for New Vaccine Development elected to forgo the option of including AIDS in this volume, because of the fact that at the time this volume was nearing completion the Institute of Medicine and the National Academy of Sciences, in consortium, had embarked on an intensive assessment of research needs and opportunities and treatment and health care issues related to AIDS. That exercise, scheduled for completion in the fall of 1986, includes consideration of vaccine prospects.

OCR for page R1
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries The committee gratefully acknowledges the assistance provided by its consultants (listed above) and other advisers listed in Appendix H. It also wishes to take particular note of the continued excellent support of the Institute of Medicine staff headed by Roy Widdus. The assistance and advice of the National Institute of Allergy and Infectious Diseases project officer, C.David Wise, is also gratefully acknowledged, as is that provided by George T.Curlin, of the Public Health Service, on behalf of the Agency for International Development. Samuel L.Katz Chairman

OCR for page R1
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries Abstract This report describes a method designed to aid government decision makers in establishing priorities for accelerated development of vaccines against diseases of importance in developing countries. The method is based on a quantitative model in which vaccine candidates are ranked according to their potential health benefits (reduction of morbidity and mortality). The model also provides the capacity to utilize “affordability” (willingness to pay for benefit) as a supplementary criterion. The approach uses the same (incomplete) information that could theoretically be used in other methods of decision making. Because the information is incomplete and because the method entails, in some instances, predicting the future, gaps must be filled by estimates or judgments by experts. Commentary is included in Chapter 1 to explain the advantages of the system and to prevent misinterpretation of the power and precision of the method. The committee believes that final selection of priorities should be made after decision makers have evaluated certain nonquantifiable considerations discussed in the report, but not incorporated into the model. These include the goals of the agency and its schedule for achieving them, considerations of equity or intent in the distribution of benefits, the opportunity and need for the agency to exert influence on development, the balance of the desired portfolio of vaccine development projects, and certain other nonquantifiable factors relating to the diseases and alternative control approaches. The method was applied to 29 vaccine candidates for 19 diseases of importance in the developing world where new or improved vaccines were judged technically feasible within the next decade. (A prior assessment considered vaccines for diseases of importance in the United States). Costs and benefits are viewed from a perspective for the developing world as a whole. The committee did not address the issues of balance between basic scientific research and vaccine development, and it expressly refrained from placing a monetary value on health benefits. An important early step in the evaluation of a potential vaccine is the selection of an appropriate target population. The committee assumed that vaccine utilization within target populations would be uniform because delivery was likely to be through the World Health Organization Expanded Program on Immunization. However, techniques are described for incorporating differential utilization, if desired. A new technique was designed to compare quantitatively the health impacts of diseases and vaccines using units of “mortality equivalents.” Elements incorporated into the calculation of a vaccine’s expected health benefit include data (and estimates) on the disease burden resulting from each pathogen, value judgments on the undesirability of conditions arising from the disease, the proportion of the disease falling in the target population, various predictions on the vaccine’s development (e.g., probability of success), and its characteristics (e.g., efficacy and the time before benefits would be achieved). The way in which value judgments on the undesirability of conditions resulting from disease (e.g., levels of acute and chronic morbidity, infertility, or death) are incorporated into the system allows quantitative expression of any perspective and an examination of its effects on the ranking. The perspective used to illustrate application of the method was

OCR for page R1
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries the median of responses from a number of health professionals in a range of developing countries. (The committee, however, does not endorse this or any other specific perspective for policy formulation in this area.) A comprehensive assessment of the net expected costs (possibly savings) associated with each vaccine candidate would include the cost of vaccine development, the likely cost of the vaccination program, the expected cost savings from treatment averted, and the cost of adverse reactions. Procedures to perform these calculations (conducted for the domestic U.S. analysis) are described in the report. For this analysis the committee judged it was not practical or realistic to attempt to estimate, for the entire developing world, the typical treatments for various disease conditions and their average costs. Thus, the cost components in this analysis relate to expenditures necessary to achieve the vaccine benefits, that is, the cost of development and the cost of vaccine for the immunization programs. (Delivery and administration costs, like utilization, are assumed to be uniform.) No “indirect” economic measures of health outcome were used. Implementing the method requires substantial amounts of information about diseases and vaccine characteristics. Data having the desired degree of reliability are not always available, however. When data are unavailable, expert judgments are required to quantify factors that are incorporated into the calculations. Scientific opinions differ on some of these judgments (e.g., the probability of success), and uncertainty surrounds much of the data (e.g., disease incidence and efficacy). The method requires the user to identify and be explicit about such factors, which the committee believes is preferable to leaving them unspecified, amorphous, or unquantified. The attempt to be explicit about certain estimates should not, however, be interpreted as an indication that a high degree of precision, unanimity, or certainty in comparisons is currently possible. The final format is flexible, can be updated as necessary to assess new vaccine candidates or to reassess current contenders, and allows users to vary estimates or predictions across a range of plausible values to determine their effects on the final result. The results from several sensitivity analyses indicate that the rank order of candidates remains fairly stable for the issues tested, which include different discount rates, probabilities of success, and various levels of financial resource constraint. Additional analyses are suggested to provide further information on the key elements that affect decisions and to indicate where new information is most needed. The table on page xi shows the categories into which the assessed vaccine candidates fall under a fairly wide range of assumptions and resource availabilities. Because certain candidates may enter different categories if other plausible assumptions are adopted, the assignments in the table should not be regarded as definitive. The committee recommends use of the method to government decision makers. The capacity to make rational choices on vaccine development priorities and vaccine formulation would be enhanced by better information on disease incidence and the pathogen serotypes prevalent in particular regions. Therefore, NIAID and other national and international agencies should consider means of improving the epidemiologic information on infectious diseases. After the committee achieved consensus on vaccine development predictions (late summer 1985), preliminary unpublished results from certain ongoing studies came to their attention. These results, if confirmed, may slightly alter the predictions on some vaccine candidates, particularly on candidates targeted against the same pathogen relative to each other, e.g., as for cholera and rotavirus. The committee did not conduct calculations based on the preliminary information but believes it would not significantly alter the overall conclusions described above; it recommends early reappraisal of candidate ranking as data from ongoing studies are publicly reported. An improved vaccine for hepatitis B virus (a polypeptide produced by recombinant DNA technology), predicted by the committee to be licensed in 1 year or less, was in fact licensed on July 24, 1986.

OCR for page R1
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries Summary of Findings: Rankings of Various Vaccine Candidates Based on Their Potential Health Benefits Under a Variety of Assumptions and Resource Constraints High Intermediate Low S.pneumoniae Plasmodium spp. (malaria; both monovalent and circumsporozoite protein-based approaches) Rotavirus (all three candidates) S.typhi (Ty21a) Shigella spp. Hepatitis B virus H.influenzae type b E.coli (either candidate) Streptococcus group A S.typhi (an aromatic amino acid-requiring strain) M.leprae V.cholerae (either candidate) Respiratory syncytial virus (either candidate) Parainfluenza Rabies (vero cell derived or glycoprotein) Hepatitis A (either candidate) N.meningitidis Yellow fever virus Dengue Rabies (live vector virus) Japanese encephalitis virus NOTE: Because certain vaccine candidates may enter different categories if other plausible assumptions are adopted, these assignments should not be regarded as definitive.

OCR for page R1
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries This page intentionally left blank.

OCR for page R1
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries Contents 1.   Summary   1 2.   Priority Setting for Health-Related Investments: A Review of Methods   19 3.   Overview of the Analytic Approach   30 4.   Comparison of Disease Burdens   44 5.   Predictions on Vaccine Development   63 6.   Assessing the Likely Utilization of New Vaccines   76 7.   Calculation and Comparison of the Health Benefits and Differential Costs Associated with Candidate Vaccines   82 8.   Additional Issues in the Selection of Priorities for Accelerated Vaccine Development   106 9.   Findings, Conclusions, and Recommendations   121 APPENDIXES     A   Selection of Vaccine Candidates for Accelerated Development   143 B   The Burden of Disease Resulting from Acute Respiratory Illness   149 C   The Burden of Disease Resulting from Diarrhea   159 D-1   The Prospects for Immunizing Against Dengue Virus   170 D-2   The Prospects for Immunizing Against Escherichia coli   178 D-3   The Prospects for Immunizing Against Hemophilus influenzae Type b   186 D-4   The Prospects for Immunizing Against Hepatitis A Virus   197 D-5   The Prospects for Immunizing Against Hepatitis B Virus   208 D-6   The Prospects for Immunizing Against Japanese Encephalitis Virus   223 D-7   The Prospects for Immunizing Against Mycobacterium leprae   241 D-8   The Prospects for Immunizing Against Neisseria meningitidis   251 D-9   The Prospects for Immunizing Against Parainfluenza Viruses   267 D-10   The Prospects for Immunizing Against Plasmodium spp.   275

OCR for page R1
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries D-11 The Prospects for Immunizing Against Rabies Virus   287 D-12   The Prospects for Immunizing Against Respiratory Syncytial Virus   299 D-13 The Prospects for Immunizing Against Rotavirus   308 D-14 The Prospects for Immunizing Against Salmonella typhi   319 D-15 The Prospects for Immunizing Against Shigella spp.   329 D-16 The Prospects for Immunizing Against Streptococcus Group A   338 D-17 The Prospects for Immunizing Against Streptococcus pneumoniae   357 D-18 The Prospects for Immunizing Against Vibrio cholerae   376 D-19 The Prospects for Immunizing Against Yellow Fever   390 E Questionnaire for Assessing Morbidity-Mortality Trade-Offs   403 F Technical Notes   412 G Biographical Notes on Committee Members   413 H Additional Sources of Advice to the Committee   418 I Contents of Supplement to Volume II   420 J Preface to Volume I   421 K Contents to Volume I   423 Index   425

OCR for page R1
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries New Vaccine Development Establishing Priorities

OCR for page R1
New Vaccine Development: Establishing Priorities, Volume II, Diseases of Importance in Developing Countries This page intentionally left blank.