COMPARATOR REPORT ON PATIENT ACCESS TO CANCER MEDICINES IN EUROPE REVISITED BENGT JÖNSSON THOMAS HOFMARCHER PETER LINDGREN IHE REPORT NILS WILKING 2016:4 COMPARATOR REPORT ON PATIENT ACCESS TO CANCER MEDICINES IN EUROPE REVISITED Authors: Bengt Jönsson, PhD, professor emeritus Stockholm School of Economics, Stockholm, Sweden Thomas Hofmarcher, MSc The Swedish Institute for Health Economics, Lund Sweden Lund University, Lund, Sweden Peter Lindgren, PhD, associate professor The Swedish Institute for Health Economics, Lund, Sweden Karolinska Institutet, Stockholm, Sweden Nils Wilking, MD, PhD, associate professor Senior strategic advisor cancer, Skåne University Hospital Lund/Malmö, Sweden Karolinska Institutet, Stockholm, Sweden IHE Report 2016:4 e-ISSN 1651-8187 The report can be downloaded from IHE’s website www.ihe.se Please cite this report as: Jönsson, B., Hofmarcher, T., Lindgren, P., Wilking, N. Comparator report on patient access to cancer medicines in Europe revisited. IHE Report 2016:4, IHE: Lund. ACCESS TO CANCER MEDICINES IN EUROPE Content Content 2 Foreword 5 List of Abbreviations 7 Executive summary 9 1 The burden and cost of cancer in Europe 1995–2014 12 1.1 Health burden of cancer 13 1.1.1 Incidence 15 1.1.2 Mortality 19 1.1.3 Survival 25 1.1.4 Burden of disease 27 Economic burden of cancer 31 Direct cost of cancer 35 1.3.1 Comparison with previous results 40 1.3.2 Development of the direct cost over time 41 1.3.3 Spending on cancer and patient outcomes 46 Cost of cancer drugs 48 1.4.1 Development of the cost of cancer drugs in absolute terms 49 1.4.2 Development of the cost of cancer drugs in relative terms 53 Indirect cost of cancer 57 1.5.1 Results from previous studies 58 1.5.2 Development of the indirect cost over time 62 Conclusion 68 1.7 References chapter 1 72 2 Medical review 78 Understanding the biology of tumour cells 79 Targeting of the cell cycle and apoptosis, DNA replication/transcription and repair 80 Targeting hormones, growth factors, and cell signalling pathways 80 Inhibiting angiogenesis 84 Immunotherapy 84 IHE REPORT 2016:4 2 www.ihe.se ACCESS TO CANCER MEDICINES IN EUROPE Companion diagnostics 85 Advances in diagnostic techniques 86 Advances in supportive drug treatment 86 Advances towards curing cancer 87 Advances towards the prevention of cancer 88 Clinical effectiveness 89 Summary and conclusion 90 References chapter 2 91 3 Access to oncology drugs 2005 – 2014 96 Definitions of access to cancer drugs and methodological aspects 96 3.1.1 Definition of cancer drugs 97 3.1.2 Measurements of sales of cancer drugs 98 3.1.3 Sales related to incidence, mortality and prevalance 100 3.1.4 Sales related to date of launch 101 Definitions used in and results from earlier studies 102 Materials and methods used in this study 105 3.3.1 Data sources 105 3.3.2 Definitions of access 105 3.3.3 Geographic scope 105 Cancer drugs 106 Top-selling drugs 112 Vintage 113 Uptake in selected therapeutic areas 114 3.7.1 Breast cancer 116 3.7.2 Chronic myeloid leukemia 123 3.7.3 Colorectal cancer 127 3.7.4 Lung cancer 132 3.7.5 Malignant melanoma 137 3.7.6 Multiple myeloma 141 3.7.7 Taxanes 145 IHE REPORT 2016:4 3 www.ihe.se ACCESS TO CANCER MEDICINES IN EUROPE Conclusions 150 References chapter 3 152 4 Policy issues for improved access to cancer medicines 153 Burden of cancer and spending on cancer care 154 Access and national health care spending 155 Access and value 160 4.3.1 ESMO-MCBS and HTA 162 4.3.2 ESMO-MCBS and uptake 163 4.3.3 Conclusions 166 Access and regulatory decision-making 167 Access, health technology assessment (HTA) and reimbursement decisions 168 Access, price and payments for new cancer medicines 171 4.6.1 Price comparisons – theory and practice 171 4.6.2 Market access agreements 175 Concluding remarks 176 References chapter 4 179 A Appendix 181 Age-standardized incidence rates 181 Age-standardized mortality rates 184 Survival rates 188 Economic preconditions and spending on health 194 Methodology for the calculation of the cancer-specific health expenditure as a share of total health expenditure 197 Summary tables of the economic burden of cancer 206 Composition of the direct cost of cancer 213 A.7.1 Distribution of the direct cost across cancer types 213 A.7.2 Distribution of the direct cost across cost categories 214 A.7.3 Distribution of the direct cost across stages of cancer 219 Composition of the indirect cost of cancer 223 IHE REPORT 2016:4 4 www.ihe.se ACCESS TO CANCER MEDICINES IN EUROPE Foreword This report is an update of a report we published in 2005 on differences between European countries in patients´ access to new cancer drugs. The background to that report was the introduction of some important new cancer medicines in the late 1990s, and the rapid increase in the costs for cancer medicines that followed after that. We recognized the need for oncologists and health economists to work together to address the issues that this new field of medical innovation created. Most important is that the increase in costs as well as the new science behind and the value of the new treatment opportunities for patients could not be seen in isolation if the objective is to develop rational policies to make best use of the new opportunities. We have thus continued to work together to study the development in cancer science and how it is translated into clinical practice, including the economic consequences and benefits for patients. In the first report we examined the ten-year period from 1995-2004 to understand the driving factors behind changes in medical oncology, and how new drugs were introduced and used in different countries. We looked into the availability of data to describe the situation, and developed a methodology for comparing access using the available data. Not surprisingly, everybody did not agree with our methods and results, and also pointed out shortcomings in the data we used. However, we noticed that we had defined the important questions, and many studies followed that challenged and complemented our findings, comparing selected groups of countries, medicines, and time periods, using mainly the same data sources, but with different definitions of access. In this report we do a follow-up of the development for the ten-year period 2005-2014 with, in principle, the same method that we used in the first study. This has the advantage that we now can gain insight into what has happened over a twenty-year period with significant scientific and clinical progress in oncology. We are also using the same type of data, which has advantages, but also creates some frustration because we had expected more progress in collecting and publishing of data that support documentation and analysis of one of the most important changes in contemporary medicine. We still lack patient specific data to assess which patients that get what treatments, and with what outcome, that can be used for international comparative studies. But in the same way as we need to make decisions about the use of new cancer medicines before we know their actual value for different patients, we need to make policy decisions based on what we know about access, costs and outcome in different countries. This is not a study with an answer to a single question and neither with a single answer to a specific question. We leave to the reader to investigate what can be learned from the report. But there are a few things that are noticeable. One is the lack of relevant data, which should be addressed. The second is that we yet have not seen any explosion in the costs for cancer care, but mainly a shift from cost for inpatient care to new cancer drugs. Spending on cancer does not reflect the burden of disease measured as share of total mortality or disability adjusted life years. You may also note from comparing this and the previous report that we do IHE REPORT 2016:4 5 www.ihe.se ACCESS TO CANCER MEDICINES IN EUROPE not think that HTA plays the significant role for access that we predicted ten years ago. The main reason is that regulatory pivotal clinical trials do not provide the data for such assessment early in development. Instead we see a much more intense discussion about initial pricing at launch of new cancer medicines, and the need for follow up data in clinical practice for assessment of value and payment by outcome. Equal access to cancer medicines remains a challenge in Europe and requires flexible pricing and reimbursement approaches that reflect the affordability levels of the different countries. Unequal access should have consequences for outcome, but we have not tried to directly link data on access to outcome in a statistical analysis. We may make a new attempt to see what the results look like in a later analysis. Finally, while we discuss policy implications and potential measures to improve access, we have no prescriptions for specific solutions. We think that rational access policies must be developed at the country level. This does not mean that collaboration and exchange of information between EU member states is discouraged. But centralized European solutions will by default focus on prices, and it is obvious that the issues are too complicated for price control to be a solution. We would like to thank Thomas Hofmarcher and Peter Lindgren for excellent research support for this updated version of the report, and Per Troin at IMS for assisting us in defining, extracting and interpretation of the data on the sales of cancer medicines 2005-2014.