Cover_WHO_nr44_Mise en page 1 2/02/16 14:34 Page 1 44 ENSURING INNOVATION IN DIAGNOSTICS FOR BACTERIAL INFECTION BACTERIAL FOR IN DIAGNOSTICS ENSURING INNOVATION IMPLICATIONS FOR POLICY FOR IMPLICATIONS Ensuring innovation 44 The inappropriate use of antibiotics is a primary cause of the ongoing increase in drug resistance amongst pathogenic bacteria. The resulting decrease in the efficacy of in diagnostics for antibiotics threatens our ability to combat infectious diseases. Rapid, point-of-care tests to identify pathogens and better target the appropriate treatment could greatly improve the use of antibiotics. Yet there are few such tests currently available or being Observatory developed despite the rapid pace of medical innovation. Clearly something is inhibiting bacterial infection Studies Series the much-needed development of new and more convenient diagnostic tools. This study delineates priorities for developing diagnostics to improve antibiotic Implications for policy prescription and use with the goal of managing and curbing the expansion of drug resistance. It calls for new approaches, particularly in the provision of diagnostic devices, and, in doing so, outlines some of the inadequacies in health, science and Edited by policy initiatives that have led to the dearth of such devices. The authors make the case Chantal Morel that there is a clear and urgent need for innovation, not only in the technology of diagnosis, but also in public policy and medical practice to support the availability and Lindsay McClure use of better diagnostic tools. Suzanne Edwards Victoria Goodfellow, Dale Sandberg, Joseph Thomas, Elias Mossialos Thomas, Joseph Dale Sandberg, Victoria Goodfellow, Suzanne Edwards, McClure, Lindsay Morel, Chantal by Edited Victoria Goodfellow This book explores the complexities of the diagnostics market from the perspective of both supply and demand, unearthing interesting bottlenecks, some obvious, some more Dale Sandberg subtle. It calls for a multifaceted and broad policy response, and an overhaul of current Joseph Thomas practice, so that the growth of bacterial resistance can be stemmed. Elias Mossialos The editors Chantal Morel, Research Officer, LSE Health (London School of Economics and Political Science), Faculty of Medicine, University of Geneva Lindsay McClure, Research Associate, LSE Health Suzanne Edwards, Research Associate, LSE Health Victoria Goodfellow, Research Associate, LSE Health Dale Sandberg, Research Associate, LSE Health Joseph Thomas, Research Assistant, LSE Health Elias Mossialos, Professor of Health Policy, LSE Health 9 7 Observatory Studies Series No. 44 8 ISBN 9289050395 9 2 8 9 0 5 0 3 9 5 Ensuring innovation in diagnostics for bacterial infection The European Observatory on Health Systems and Policies supports and promotes evidence-based health policy-making through comprehensive and rigorous analysis of health systems in Europe. It brings together a wide range of policy-makers, academics and practitioners to analyse trends in health reform, drawing on experience from across Europe to illuminate policy issues. The Observatory is a partnership hosted by the WHO Regional Office for Europe; which includes the governments of Austria, Belgium, Finland, Ireland, Norway, Slovenia, Sweden, the United Kingdom, and the Veneto Region of Italy; the European Commission; the World Bank; UNCAM (French National Union of Health Insurance Funds); the London School of Economics and Political Science; and the London School of Hygiene & Tropical Medicine. The Observatory has a secretariat in Brussels and it has hubs in London (at LSE and LSHTM) and at the Technical University of Berlin. Ensuring innovation in diagnostics for bacterial infection Implications for policy Edited by Chantal Morel Research Officer, LSE Health (London School of Economics and Political Science), Faculty of Medicine, University of Geneva Lindsay McClure Research Associate, LSE Health Suzanne Edwards Research Associate, LSE Health Victoria Goodfellow Research Associate, LSE Health Dale Sandberg Research Associate, LSE Health Joseph Thomas Research Assistant, LSE Health Elias Mossialos Professor of Health Policy, LSE Health © World Health Organization 2016 (acting as the host organization for, and secretariat of, the European Observatory on Health Systems and Policies) Address requests about publications to: Publications, WHO Regional Office for Europe, UN City, Marmorvej 51, DK-2100 Copenhagen Ø, Denmark. Alternatively, complete an online request form for documentation, health information, or for permission to quote or translate, on the Regional Office web site (http://www.euro.who.int/ pubrequest). All rights reserved. The European Observatory on Health Systems and Policies welcomes requests for permission to reproduce or translate its publications, in part or in full. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the European Observatory on Health Systems and Policies concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the European Observatory on Health Systems and Policies in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by the European Observatory on Health Systems and Policies to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either express or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the European Observatory on Health Systems and Policies be liable for damages arising from its use. The views expressed by authors, editors, or expert groups do not necessarily represent the decisions or the stated policy of the European Observatory on Health Systems and Policies or any of its partners. ISBN 978 92 890 50364 Printed in the United Kingdom Cover design by M2M Table of contents Acknowledgements ix List of abbreviations xi List of tables and figures xv 1. Introduction 1 2. Background 3 2.1 Trends in the use and misuse of antibiotics 3 2.2 Trends in the prevalence of resistance 7 3. Overview of the diagnostics market 13 3.1 Introduction 13 3.2 Shape and size of the market 13 3.3 Recent trends in the market 16 3.4 Exhibits: examples of recent breakthroughs in diagnostic development 25 4. Supply-side bottlenecks inhibiting development of priority diagnostics 33 4.1 Introduction 33 4.2 Drivers of resource allocation decisions by developers and prospective diagnostic developers 33 4.3 Scientific and technical barriers 40 5. Reimbursement-related signals received from procurement and reimbursement agencies 57 5.1 Introduction 57 5.2 Background: reimbursement in the United States 57 5.3 Coverage: determining clinical utility 58 5.4 Background: overview of reimbursement of diagnostics in the United Kingdom and Europe 77 5.5 Implications of being tied to indication 81 5.6 Variation across countries 84 5.7 Reimbursement case study 86 vi Ensuring innovation in diagnostics for bacterial infection 6. Regulation 89 6.1 Introduction 89 6.2 History of medical device regulation 89 6.3 Evolving needs for medical device regulation 90 6.4 Overview of regulatory processes for market entry in Europe and the United States 90 6.5 United States current regulatory structures/frameworks 92 6.6 EU current regulatory structures/framework 102 6.7 Reform under way in the United States 108 6.8 Reforms under way in Europe 115 6.9 Industry stakeholder involvement in European regulatory reforms 118 6.10 Evaluation of communication pathways between regulator and industry 118 6.11 FDA flexibility in antibiotic approval/trial design which may influence uptake of diagnostics 121 6.12 Flexibility in clinical trial requirements for antibiotic development 121 6.13 Regulatory comparison United States/EU 122 6.14 Harmonization of the diagnostics regulatory pathway in the United States and EU 125 6.15 Industry perspectives on harmonization 128 6.16 Stakeholder perception of overall regulatory processes for diagnostics 129 7. Intellectual property challenges 133 7.1 Introduction 133 7.2 History 133 7.3 Patent-related bottlenecks to diagnostic development 136 8. Demand-side issues 145 8.1 Introduction: complexity in demand expression 145 8.2 Engagement to improve developer understanding of demand 146 8.3 Determinants of and barriers to uptake of new POC diagnostics 148 8.4 Diagnostic and clinical guidelines 155 8.5 Prescribing culture 161 8.6 Patient barriers 164 9. Economic evaluation: the limited evidence base affecting both supply and demand for new diagnostics 165 9.1 Introduction 165 9.2 Background: economic evaluation and cost–effectiveness 165 9.3 Background: economic evaluation in the United States 167 9.4 Background: summary of the evidence from economic evaluations of rapid POC diagnostics 170 9.5 Challenges in making the “business case” for new diagnostics 178 Table of contents vii 9.6 Need for greater role of public sector in setting format priorities 182 9.7 Cost–effectiveness evidence in reimbursement