Regulatory and Economic Aspects in Oncology (Recent Results in Cancer Research, 213)

This book explores topics of importance to all who have an interest in economic methods for assessment of the efficacy and effectiveness of new cancer treatments and in regulatory measures relating to their marketing authorization and pricing. Targeted therapies and modern immunotherapy are placing a substantial strain on health care budgets. Regulation and economic methods to assess the parameters for establishing efficacy and effectiveness are therefore of prime importance. Payer authorities have to determine whether the use of these novel therapies yields clinical benefits that justify their increasing cost. In the simplest terms, cost-effectiveness analyses quantify the ratio between the extent to which an intervention raises healthcare costs and the extent to which it improves health outcomes. Rigorous cost-effectiveness analyses translate all health outcomes into quality-adjusted life years. On the other hand, in order to sustain innovation, price regulations must be coupled with efforts to ensure that drug companies are still able to recoup their investments in high-risk and high-costs research programs. Ultimately, decisions regarding health care expenditures are also a question of society’s willingness to pay. Contents 6 About the Editor 8 1 Introduction and Overview 9 Abstract 9 References 12 2 Cost of Cancer: Healthcare Expenditures and Economic Impact 14 Abstract 14 1 Introduction 15 2 Methods 16 3 Total Health Expenditures on Cancer 16 4 Spending on Cancer Drugs 19 5 Resource Use Outside the Healthcare Sector for Care of Cancer Patients 22 6 Resources Lost Due to Economic Impact on Persons with Cancer 23 7 Loss of Health in Economic Terms 26 8 Summary and Conclusions 27 References 30 3 Oncology from an HTA and Health Economic Perspective 31 Abstract 31 1 Introduction 32 2 Brief Overview of Cost-Effectiveness Models in Oncology 34 3 Issue with Clinical Inputs Due to Crossover (Switch) in Randomised Clinical Trials 35 4 Need for Survival Extrapolation and Limitations with Current Parametric Model 37 5 Rare Indications with Limited Economic and Comparative Evidence Available 39 6 High Pace of Clinical Development 40 7 Further Issues with Health Economic Models in Oncology 40 7.1 Health-Related Quality of Life 40 8 Comparator and Off-Label 41 9 Cost-Effectiveness Vs Affordability 41 10 Conclusion 42 References 42 4 Heterogeneous Recommendations for Oncology Products Among Different HTA Systems: A Comparative Assessment 45 Abstract 45 1 Introduction 46 2 Brief Overview of Selected HTA Agencies 47 2.1 France—HAS 47 2.2 Germany—IQWiG/G-BA 47 2.3 UK—England—NICE 48 2.4 UK—Scotland—SMC 49 2.5 Sweden 49 2.6 Australia 50 2.7 Canada 50 3 Comparison of HTA Decision-Making Frameworks 51 3.1 HTA Outcomes 51 3.2 HTA Aspects Specific to Oncology 53 4 Evaluation Criteria and Processes in HTA 54 4.1 Cross-Country Comparison of HTA Recommendations in Oncology 56 5 Conclusion 59 References 60 5 Patient-Reported Outcomes in Oncology, Beyond Randomized Controlled Trials 62 Abstract 62 1 Introduction 63 2 Patient Perspective Differs from HealthCare Professional Perspective 63 3 Definition of PROs and Classification 64 4 PROs in Oncology Clinical Trials 64 5 Validity of PRO Instruments 66 6 Other Methods to Capture Patient’s Perspectives 66 7 Value of PRO in Oncology 67 References 68 6 Patient-Reported Outcomes in Health Economic Decision-Making: A Changing Landscape in Oncology 71 Abstract 71 1 Introduction 72 2 Global Oncology Snapshot 73 3 Reframing the Value Equation 74 4 Patient-Centered Care and Patient-Reported Outcomes 75 5 Investments in PRO Measures 76 6 Challenges and Potential Solutions 79 7 Conclusion 83 References 83 7 Approaches to Capturing Value in Oncology 88 Abstract 88 1 Introduction 89 2 Value—An Ambiguous Concept 90 3 Quality-Adjusted Life Years (QALY) and ICERs Core Metrics 91 4 The Five Value Frameworks 93 4.1 The ESMO Magnitude of Clinical Benefit Scale 93 4.2 The American Society of Clinical Oncology (ASCO) Value Framework 96 4.3 National Comprehensive Cancer Network Evidence Blocks 97 4.4 Memorial Sloan Kettering Cancer Center DrugAbacus 98 4.5 The Institute for Clinical and Economic Review Value Assessment Framework 98 5 Are Frameworks a Boon or a Bane? 99 5.1 Clinical Trial Data Versus Real-World Evidence 99 5.2 Method of Scoring 100 5.3 Problems with QALYs 100 5.4 Perspective (Payer, Policymaker, Physician, Patient) 102 5.5 Including Costs 102 6 MCBS Versus ICER 103 7 Future Perspectives 106 8 Conclusion 106 References 107 8 Orphan Drugs in Oncology 112 Abstract 112 1 Introduction 113 2 Orphan Drugs: Regulatory Process 114 3 Orphan Drugs: Health Technology Assessment and Pricing 115 4 Orphan Drugs in Oncology 118 4.1 Overview 118 4.2 HTA Outcomes for Orphan Drugs in Oncology: Example of France, Germany and England 126 4.3 High Costs of Oncology Orphan Drugs 137 4.4 Future Perspectives 139 5 Conclusion 141 References 141 9 Recent Developments in Health Economic Modelling of Cancer Therapies 146 Abstract 146 1 Summary of the Standard Three-State Partitioned Survival Model 146 2 Survival Curve Analysis 148 3 Newer Methods Such as Piecewise Curve Fitting and ‘Mixed Cure’ Models 149 4 How to Deal with Crossover or Single Arm Trials 150 5 Utilities—The Ways in Which Utilities Can Be Applied, Applying Utilities with Proximity to Death 151 6 The Economic Implications of Increased Survival in Oncology 153 References 153 10 Drug Pricing and Value in Oncology 155 Abstract 155 1 Introduction 155 2 Evidence on Expenditures and Price Growth for Cancer Drugs 157 2.1 Expenditures 157 2.2 Launch Price Trends 157 2.3 Price Growth Post-launch: Measurement Issues 158 3 Drivers of High Prices for Cancer Drugs: Reimbursement Rules Matter 160 3.1 Reimbursement Rules and Pricing Incentives in the USA 160 3.2 Pricing in Developed Countries Ex-USA 164 4 R&D and Pricing 165 5 Value-Based Pricing: A Way Forward 166 5.1 Value-Based Pricing 166 6 Conclusion 168 References 168 11 Regulatory and Evidence Requirements and the Changing Landscape in Regulation for Marketing Authorisation 170 Abstract 170 1 Introduction 170 2 Requirements for Marketing Authorisation 172 3 Special Types of Marketing Authorisations 174 4 Demonstration of Efficacy and Positive Benefit-Risk Balance 176 5 Experience Interpreting the Regulatory Requirements 177 6 Orphan Medicinal Products, Protection, Exclusivity and Other Incentives 178 7 Paediatric Requirements for Medicinal Products 181 8 Efforts to Improve Timely Access to New Medicines 181 9 Guidelines on Clinical Drug Development of Anticancer Medicinal Products 183 9.1 Summary 186 References 186 12 Prioritization not Rationing in Cancer Care 189 Abstract 189 1 Introduction 190 2 Clarifying Terms 191 3 Economic Discussion Regarding Scarcity and Medical Decision-Making 193 4 Ethical Decision-Making Framework 195 5 Heterogenization and Comparison Analysis Provide Innovation-Oriented and Value-Generating Framework 197 6 Order Ethics Provides Framework for Responsible Cancer-Care Prioritization 200 7 Conclusion 203 Acknowledgements 203 References 204 Front Matter ....Pages i-vii Introduction and Overview (Evelyn Walter)....Pages 1-5 Cost of Cancer: Healthcare Expenditures and Economic Impact (Bengt Jönsson)....Pages 7-23 Oncology from an HTA and Health Economic Perspective (Clement Francois, Junwen Zhou, Michał Pochopien, Leila Achour, Mondher Toumi)....Pages 25-38 Heterogeneous Recommendations for Oncology Products Among Different HTA Systems: A Comparative Assessment (Szymon Jarosławski, Eve Hanna, Monique Dabbous, Lylia Chachoua, Mondher Toumi)....Pages 39-55 Patient-Reported Outcomes in Oncology, Beyond Randomized Controlled Trials (Mondher Toumi, Szymon Jarosławski, Christos Chouhaid, Bruno Fallissard, P. Auquier)....Pages 57-65 Patient-Reported Outcomes in Health Economic Decision-Making: A Changing Landscape in Oncology (Mandi Pratt-Chapman, Afsan Bhadelia)....Pages 67-83 Approaches to Capturing Value in Oncology (Evelyn Walter)....Pages 85-108 Orphan Drugs in Oncology (Daria Korchagina, Szymon Jaroslawski, Guy Jadot, Mondher Toumi)....Pages 109-142 Recent Developments in Health Economic Modelling of Cancer Therapies (William Green, Matthew Taylor)....Pages 143-151 Drug Pricing and Value in Oncology (Patricia M. Danzon)....Pages 153-167 Regulatory and Evidence Requirements and the Changing Landscape in Regulation for Marketing Authorisation (Francesco Pignatti, Elias Péan)....Pages 169-187 Prioritization not Rationing in Cancer Care (Nikolaus Knoepffler, Jürgen Zerth, Martin O’Malley)....Pages 189-205 This book explores a wide range of topics of importance to all those who have an interest in economic methods for assessment of the efficacy and effectiveness of new cancer treatments and in regulatory measures relating to the marketing authorization and pricing of such treatments. It also examines drug pricing and drug price regulation in different countries and explores the changing landscape in marketing authorization and its regulation. These issues are becoming increasingly important with the introduction of expensive targeted cancer therapies, which are placing a substantial strain on healthcare healthcare budgets. Payer authorities have to determine whether the use of targeted therapies yields clinical benefits that justify their cost. In the simplest terms, cost-effectiveness analysis quantifies the ratio between the extent to which an intervention raises healthcare costs and the extent to which it improves health outcomes. Rigorous cost-effectiveness analyses translate all health outcomes into quality-adjusted life years. On the other hand, in order to sustain innovation, price regulation must be coupled with efforts to ensure that drug companies are still able to recoup their investments in high-risk and high-cost research programs. Ultimately, decisions regarding health care expenditure are also a reflection of society's willingness to pay This book provides an up to date user friendly resource on the emerging field of digital medicine and its present and potential future role in modern healthcare. 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