A structured methodology for essential medicines lists and health emergency stockpiles: Experience with the Emergency Medicines Buffer Stock in the United Kingdom.

INTRODUCTION: Formularies of essential medicines, such as Essential Medicines Lists (EMLs) and health emergency stockpiles, are intended to be always available, including in emergency situations, acting as important tools for access to medicines. The Emergency Medicines Buffer Stock (EMBS) in the United Kingdom (UK) was a stockpile of critical medicines managed by the UK Department of Health and Social Care (DHSC). We propose a new methodology for selecting and including medicines in EMLs and health emergency stockpiles and empirically apply it for selecting medicines in the case of the UK EMBS. METHODS: We used Multi-Attribute Value Theory and Portfolio Decision Analysis to develop a three-phase methodological framework for medicines selection, involving: (i) the decision context definition and selection of evaluation criteria, (ii) the therapeutic area prioritisation, and (iii) the medicines value-for-money evaluation and product selection. The EMBS application took place in 2018-2019 and focused on therapeutic area prioritisation, involving primary data collection through expert interviews (n = 4), a workshop with DHSC decision-makers (n = 13), and an online survey with National Clinical Directors and relevant experts (n = 24). A Monte Carlo simulation supported therapeutic area prioritisation using the British National Formulary (BNF) classification. FINDINGS: Two criteria sets were selected for i) therapeutic area prioritisation, reflecting the value concerns of population need and shortage severity, and ii) medicines evaluation, reflecting magnitude of clinical benefit and supply vulnerability, among others. Primary evidence was collected for "national need" and "shortage severity", based on which a "population health loss" index was developed. A total of 51 therapeutic areas were ranked using their index value while assessing the robustness of the ranking. The top ranked therapeutic area was antisecretory drugs and mucosal protectants, closely followed by diabetes drugs. CONCLUSIONS: The methodological application generated a ranking of therapeutic areas based on expected "population health loss" index, while addressing evidence uncertainty. The methodology can be adapted for other EMLs and emergency stockpile contexts to inform medicines selection.

Understanding the socioeconomic costs of dystrophic epidermolysis bullosa in Europe: a costing and health-related quality of life study.

BACKGROUND: Dystrophic epidermolysis bullosa (EB) is a family of rare genetic dermatological conditions. Recent evidence indicated that in addition to its detrimental implications on patient health-related quality of life (HRQoL), there are substantial socioeconomic cost implications, especially regarding direct non-medical costs. This study aims to understand the burden of dystrophic EB (DEB) in Europe, using a primary EB patient-level dataset. METHODS: A bottom-up, cross-sectional, study design was adopted for non-institutionalised patients diagnosed with EB who received outpatient care across EU5 countries: France, Germany, Italy, Spain, and the United Kingdom. A prevalence-based approach was used to estimate resource utilisation from a societal perspective, including direct (medical and non-medical) and indirect costs for patients and caregivers. Patient and caregiver outcomes were obtained using the EQ-5D questionnaire. RESULTS: A sample of 91 DEB patients was analysed. Overall, average EU5 annual cost per patient was estimated at €53,359, ranging from €18,783 (France) to €79,405 (Germany). Average EU5 annual direct medical costs were estimated at €8357 (15.7% of total), ranging from €5658 (France) to €12,576 (Germany); average direct non-medical costs were estimated at €41,353 (77.5% of total), ranging from €11,961 (France) to €57,000 (Germany); and average indirect costs were estimated at €3649 (6.8% of total), ranging from €1025 (Italy) to €9930 (United Kingdom). Costs varied across patients with different disability but also between children and adults. The mean EQ-5D index score for adult DEB patients ranged between 0.304 (United Kingdom) and 0.541 (Germany), with an EU5 average of 0.456, whereas the mean EQ-5D visual analogue scale score ranged between 47.5 (Germany) and 70.0 (France), with an EU5 average of 61.9. Limitations included potential patient selection bias, recall bias, and exclusion of bandaging and related costs. CONCLUSIONS: The study revealed a substantial socioeconomic burden for DEB in Europe, attributable mostly to high direct non-medical costs, with the majority of patients requiring support from caregivers at home. Compared to the average economic burden of the overall EB patient population, costs for DEB patients are higher across all components of direct medical, direct non-medical and indirect costs.

Multiple Criteria Decision Analysis for HTA across four EU Member States: Piloting the Advance Value Framework.

Multiple Criteria Decision Analysis (MCDA) has emerged as a methodology for Health Technology Assessment (HTA). However, limited empirical evidence is available on its use by decision-makers; where available, it only comes from single-setting exercises, while cross-country comparative studies are unavailable. This study applies the Advance Value Framework (AVF), an MCDA methodology for HTA based on multi-attribute value theory, through a series of case studies with decision-makers in four countries, to explore its feasibility and compare decision-makers' value preferences and results. The AVF was applied in the evaluation of three drugs for metastatic, castrate resistant, prostate cancer (abiraterone, cabazitaxel and enzalutamide) in the post-chemotherapy indication. Decision conferences were organised in four European countries in collaboration with their HTA or health insurance organisations by involving relevant assessors and experts: Sweden (TLV), Andalusia/Spain (AETSA), Poland (AOTMiT) and Belgium (INAMI-RIZIV). Participants' value preferences, including performance scoring and criteria weighting, were elicited through a facilitated decision-analysis modelling approach using the MACBETH technique. Between 6 and 11 criteria were included in each jurisdiction's value model, allocated across four criteria domains; Therapeutic Benefit criteria consistently ranked first in relative importance across all countries. Consistent drug rankings were observed in all settings, with enzalutamide generating the highest overall weighted preference value (WPV) score, followed by abiraterone and cabazitaxel. Dividing drugs' overall WPV scores by their costs produced the lowest "cost per unit of value" for enzalutamide, followed by abiraterone and cabazitaxel. These results come in contrast with the actual country HTA recommendations and pricing decisions. Overall, although some differences in value preferences were observed between countries, drug rankings remained the same. The MCDA methodology employed could act as a decision support tool in HTA, due to the transparency in the construction of value preferences in a collaborative manner.

Using a stated preference discrete choice experiment to assess societal value from the perspective of decision-makers in Europe. Does it work for rare diseases?

OBJECTIVES: To pilot the feasibility of using a discrete choice experiment (DCE) design to investigate individual preferences from the decision-maker perspective regarding the use of public funding for orphan drugs and generate prior information for future experimental designs. METHODS: A DCE was used on a convenience sample of participants from five European countries (England, France, Germany, Italy and Spain), exploring their preferences in distinct healthcare scenarios involving orphan drugs. A preliminary review of the empirical literature on distributive preferences informed the selection of attributes and their levels in the design. An online questionnaire was used to conduct the DCE survey. RESULTS: A total of 199 questionnaires were completed. The five country model showed relative preference for some attributes over others: cost of treatment, improvement in health, value for money and availability of treatment alternatives received the greatest attention. However, disease severity, beginning of life, waiting times and side effects were also shown to be important social values that should not be ignored. CONCLUSIONS: The findings presented in this study provide insight about the preferences that can influence decisions on orphan drugs in different countries. This study also provides valuable prior information that could inform future DCE designs in this area.

Social/economic costs and health-related quality of life in patients with juvenile idiopathic arthritis in Europe.

OBJECTIVE: The aim of this study was to determine the economic burden from a societal perspective and the health-related quality of life (HRQOL) of patients with juvenile idiopathic arthritis (JIA) in Europe. METHODS: We conducted a cross-sectional study of patients with JIA from Germany, Italy, Spain, France, the United Kingdom, Bulgaria, and Sweden. Data on demographic characteristics, healthcare resource utilization, informal care, labor productivity losses, and HRQOL were collected from the questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D-5L) questionnaire. RESULTS: A total of 162 patients (67 Germany, 34 Sweden, 33 Italy, 23 United Kingdom, 4 France, and 1 Bulgaria) completed the questionnaire. Excluding Bulgarian results, due to small sample size, country-specific annual health care costs ranged from €18,913 to €36,396 (reference year: 2012). Estimated direct healthcare costs ranged from €11,068 to €22,138; direct non-healthcare costs ranged from €7837 to €14,155 and labor productivity losses ranged from €0 to €8715. Costs are also shown to differ between children and adults. The mean EQ-5D index score for JIA patients was estimated at between 0.44 and 0.88, and the mean EQ-5D visual analogue scale score was estimated at between 62 and 79. CONCLUSIONS: JIA patients incur considerable societal costs and experience substantial deterioration in HRQOL in some countries. Compared with previous studies, our results show a remarkable increase in annual healthcare costs for JIA patients. Reasons for the increase are the inclusion of non-professional caregiver costs, a wider use of biologics, and longer hospital stays.

Addressing barriers to the prevention, diagnosis and treatment of hepatitis B and C in the face of persisting fiscal constraints in Europe: report from a high level conference.

In the WHO-EURO region, around 28 million people are currently living with chronic viral hepatitis, and 120,000 people die every year because of it. Lack of awareness and understanding combined with the social stigma and discrimination exacerbate barriers related to access to prevention, diagnosis and treatment services for those most in need. In addition, the persisting economic crisis has impacted on public health spending, thus posing challenges on the sustainable investment in promotion, primary and secondary prevention, diagnosis and treatment of viral hepatitis across European countries. The Hepatitis B and C Public Policy Association in cooperation with the Hellenic Center for Disease Prevention and Control together with 10 partner organizations discussed at the Athens High Level Meeting held in June 2014 recent policy developments, persisting and emerging challenges related to the prevention and management of viral hepatitis and the need for a de minimis framework of urgent priorities for action, reflected in a Call to Action (Appendix S1). The discussion confirmed that persisting barriers do not allow the full realisation of the public health potential of diagnosing and preventing hepatitis B and C, treating hepatitis B and curing hepatitis C. Such barriers are related to (a) lack of evidence-based knowledge of hepatitis B and C, (b) limited access to prevention, diagnosis and treatment services with poor patient pathways, (c) declining resources and (d) the presence of social stigma and discrimination. The discussion also confirmed the emerging importance of fiscal constraints on the ability of policymakers to adequately address viral hepatitis challenges, particularly through increasing coverage of newer therapies. In Europe, it is critical that public policy bodies urgently agree on a conceptual framework for addressing the existing and emerging barriers to managing viral hepatitis. Such a framework would ensure all health systems share a common understanding of definitions and indicators and look to integrate their responses to manage policy spillovers in the most cost-effective manner, while forging wide partnerships to sustainably and successfully address viral hepatitis.

The rising burden of cancer in the developing world.

Cancer remains one of the leading causes of morbidity and mortality worldwide. It is predicted that by 2020, the number of new cases of cancer in the world will increase to more than 15 million, with deaths increasing to 12 million. Much of the burden of cancer incidence, morbidity, and mortality will occur in the developing world. This forms part of a larger epidemiological transition in which the burden of chronic, non-communicable disease-once limited to industrialized nations-is now increasing in less developed countries. In addition to the accumulating risks associated with diet, tobacco, alcohol, lack of exercise, and industrial exposures, the developing world is already burdened by cancers some of which are attributable to infectious diseases. These disparities in cancer risk combined with poor access to epidemiological data, research, treatment, and cancer control and prevention combine to result in significantly poorer survival rates in developing countries for a range of specific malignancies. This paper summarizes the recent trends in the epidemiology and survival of cancers in the developing and developed world, and explores potential causes and policy responses to the disproportionate and growing cancer burden in less developed countries. Such responses may include raising awareness as well as education and training to foster better informed decision-making, together with improved cancer surveillance, early detection and emphasis on prevention. Improved health care financing and international initiatives and/or partnerships could also provide additional impetus in targeting resources where needed urgently.

Can economic evaluation guidelines improve efficiency in resource allocation? The cases of Portugal, The Netherlands, Finland, and the United Kingdom.

The use of economic evaluation in decision making appears to have increased over the past few years and economic evaluation is looked upon as another measure to help contain costs and improve efficiency in an evidence-based decision-making environment. Following the examples of Australia and the Canadian Province of Ontario, four European Union (EU) countries (Finland, the Netherlands, Portugal, and the United Kingdom) have recently introduced economic evaluation guidelines. In addition to the Australian and Canadian guidelines, which constitute a hurdle to reimbursement, the paradigm that seems to be evolving in the four EU countries follows a similar route. Finland and the Netherlands seem to be moving toward the notion of a fourth hurdle to reimbursement, whereas the National Institute for Clinical Excellence in England and Wales was in principle meant to influence practice, although in reality this essentially acts as a hurdle to reimbursement, requiring a different data set to that used by regulatory authorities. Whereas the Portuguese guidelines were developed to assist in preparing economic submissions to support reimbursement decisions, they are unclear about when such evidence will be required and also discuss the dissemination of economic evidence to broader audiences. The introduction of these guidelines poses a number of challenges to policy makers, the implications of which are analyzed in the paper: a) to ensure that economic evaluations are carried out scientifically without industrial or political bias; b) to define an acceptable methodology that would increase their credibility; and c) to address certain practical issues ranging from deciding how to use economic evaluations in policy making to setting up new institutions or improving the coordination and dissemination of evidence. The variation in the use of economic evaluation guidelines in the four EU countries highlights the differences in national pharmaceutical policies and is in line with policy makers' continuous attempts to contain costs. While the paper critically discusses the guidelines, it also points out that a series of methodologic issues need to be addressed if economic criteria are to be introduced in policy making with the aim to improve resource allocation. The paper concludes that economic evaluation as a discipline is beginning to impact on policy, whereas the consistent use of economic evaluation results is, in principle, being adopted by policy makers but needs to go a step further to reach practitioners.

Cross-border issues in the provision of health services: are we moving towards a European health care policy?

This paper analyses likely implications of two recent European Court rulings on the provision of health care across borders within the European Union. We argue that the two cases have fundamental implications for the provision of health services as free access to care across borders conflicts with the principle of subsidiarity. We then explore the potential short- and long-term implications of the two cases for all involved in the provision of health services, namely patients, different types of purchasers and different types of providers. We argue that the short-term implications relating to freedom to provide goods and services may lead to re-thinking how services are financed and provided. At the same time, the rulings may lead to greater transparency in health services, with attempts to compare efficiency and prices between providers in different countries. Consumers may benefit directly by gaining access to a product or service that is not available in their country of residence or is available but at a higher cost or lower quality. They may also benefit indirectly in the long term, through greater transparency and efficiency.

The single market for pharmaceuticals in the European Union in light of European Court of Justice rulings.

This article analyses the likely implications for the European pharmaceutical market of 2 European Court rulings (Kohll and Decker) and addresses whether these will contribute to the completion of the single European market. In doing so, the Kohll and Decker cases are discussed and the likely implications of these cases for key stakeholders (patients, providers, payers and the industry) are investigated. Of the 2 cases, the latter has direct application to pharmaceuticals as tradable goods. The article argues that the short term implications for the stakeholders, relating to the freedom of providing goods, may lead to a re-thinking of how pharmaceutical products are financed and provided in European Union (EU) countries in the long term. A key corollary of the Decker case is that it leads to greater transparency and awareness of pharmaceutical price differentials across the member states. As part of this transparency, consumers may benefit directly by gaining access to a product that may not be available in their country of residence, or may be available but at a higher cost. Consumers may also benefit indirectly through greater transparency and efficiency in the long term. Providers may wish to increase their procurement from cheaper sources of the same product and much will depend on their future procurement strategies. Manufacturers will in this case face an increase in parallel trade streams and may respond by not marketing or producing in 'low-price' countries. The rulings add a further supranational dimension to a national policy issue and may have far reaching implications for the EU pharmaceutical market and industry.

Outstanding regulatory aspects in the European pharmaceutical market.

This paper identifies and analyses a number of outstanding regulatory aspects in the completion of the European pharmaceutical single market. It discusses pricing and competition in pharmaceuticals in the aftermath of the 3 Frankfurt Roundtables and their results. It analyses the environment for generic competition in the European Union (EU) and the extent to which this environment needs to be amended in order for such competition to be promoted. It links the issues of parallel trade, standardisation, single trademark, the European databank and the definition of innovation with the current situation in the functioning of the single market, particularly the sovereignty of the member states in determining pricing and reimbursement levels. It argues that the above problems need to be tackled in conjunction with pricing and reimbursement. The paper further points at new developments, in particular biotechnology patenting and orphan drug regulation, where the EU has introduced or is about to introduce new legislation that has been needed for a long time and examines how this legislation can be beneficial. Finally, the paper analyses the implications for healthcare provision in the member states of 2 legal cases heard before the European Court of Justice in relation to the free movement of goods and healthcare provided across borders. The paper concludes that there is still a long list of regulatory aspects that remain unresolved despite the fact that significant progress has been made to date, and observes that economic analysis in pharmaceutical regulation is very much intertwined with political expediency. In addition, the definition of political expediency varies as one considers developments at the EU or national level, since it does not necessarily follow that individual actors coincide in opinion.

International comparisons of health care expenditures: what we know and what we do not know.

International comparisons of health care expenditures and their determinants have attracted considerable attention since the early 1960s and have since been used widely to compare countries. The impetus for this has been two-fold: firstly, to assess the macroeconomic efficiency of health systems by determining whether different methods of financing and delivering health care have contributed to the control of overall spending levels; and, secondly, to investigate the determinants of the level of health care expenditure. Empirical research has suggested that there is a causal and statistically significant relationship between growth in health spending and growth in gross domestic product (GDP), and that an increase in the latter brings about a proportionately larger increase in the former. This relationship holds even when other potential determinants, such as urbanisation and age structure of the population, are included in the analysis, leading to the conclusion that health care is a luxury good. This paper examines the extent to which this finding is valid from a methodological perspective and how far it assists policy analysis. We argue that there are significant problems in the measurement of health spending and GDP, discuss the methodological problems in the analysis and suggest that the observed relationship between GDP and health spending is unhelpful and almost certainly misleading for health policy development.

Financing pharmaceuticals in transition economies.

This paper (a) provides a methodological taxonomy of pricing, financing, reimbursement, and cost containment methodologies for pharmaceuticals; (b) analyzes complex agency relationships and the health versus industrial policy tradeoff; (c) pinpoints financing measures to balance safety and effectiveness of medicines and their affordability by publicly funded systems in transition; and (d) highlights viable options for policy-makers for the financing of pharmaceuticals in transition. Three categories of measures and their implications for pharmaceutical policy cost containing are analyzed: supply-side measures, targeting manufacturers, proxy demand-side measures, targeting physicians and pharmacists, and demand-side measures, targeting patients. In pursuing supply side measures, we explore free pricing for pharmaceuticals, direct price controls, cost-plus and cost pricing, average pricing and international price comparisons, profit control, reference pricing, the introduction of a fourth hurdle, positive and negative lists, and other price control measures. The analysis of proxy-demand measures includes budgets for physicians, generic policies, practice guidelines, monitoring the authorizing behavior of physicians, and disease management schemes. Demand-side measures explore the effectiveness of patient co-payments, the impact of allowing products over-the-counter and health promotion programs. Global policies should operate simultaneously on the supply, the proxy demand, and the demand-side. Policy-making needs to have a continuous long-term planning. The importation of policies into transition economy may require extensive and expensive adaptation, and/or lead to sub-optimal policy outcomes.

A prospective view on European pharmaceutical research and development. Policy options to reduce fragmentation and increase competitiveness.

This article analyses 3 areas of policy that could reduce the fragmentation and improve the competitiveness of the European pharmaceutical sector. It argues that a potential solution to the issue of fragmentation of pharmaceutical research, development and innovation may be the development of policies at the European level, in those areas that European institutions have a competence. These areas may not necessarily rely exclusively on solving the issue of pricing and reimbursing pharmaceuticals as European Union (EU) Member States invoke the subsidiarity principle to claim policy exclusivity in this area. By contrast, policy areas where European institutions have a competence may include: i) a more intensified collaboration in science and technology policy (supporting the science base, identifying education needs for the future, collaborating in the development of new technologies and fostering university-industry collaboration); ii) support of research and development (R&D) by means of directly channelling funds into basic pharmaceutical research, avoiding duplication of the research effort, developing a set of research priorities, tackling the issue of technology transfer, promoting university-industry and cross-border collaborations or providing incentives that would induce private R&D activities in areas with large socioeconomic impact; and iii) an improvement in the environment for the financing of innovation in the EU, by means of selective use of tax policy at the national level (and where applicable, at the EU level), institutional reform in order to widen the pool of available funds for private investment, and the introduction of schemes that would encourage individuals and institutions to hold equity in innovative companies. The article identifies specific research, regulatory, medical and financing needs that require policy intervention, evaluates the possible dynamic implications of such interventions and highlights the benefits that may accrue from their implementation.

Single European currency and Monetary Union. Macroeconomic implications for pharmaceutical spending.

This article examines the potential implications of introducing a single currency among the Member States of the European Union for national pharmaceutical prices and spending. In doing so, it provides a brief account of the direct effects of introducing a single currency on pharmaceutical business. These are static in nature and include the elimination of exchange rate volatility and transaction costs, increased price transparency and limited potential for parallel trade. It subsequently analyses the potential medium and long term macroeconomic policy choices facing the Member States and their impact on pharmaceutical spending following the introduction of a single currency. These include policy directions in order to meet the Maastricht convergence criteria in the run-up to forming an Economic and Monetary Union (EMU) and the implications of EMU on national macroeconomic policy thereafter. This article argues that the necessity for tight fiscal policies across the EU and, in particular, in those Member States facing high budget deficits and overall debt levels, will continue to exert considerable downward pressure on pharmaceutical spending.