Potential approaches for the pricing of cancer medicines across Europe to enhance the sustainability of healthcare systems and the implications.

Introduction: There are growing concerns among European health authorities regarding increasing prices for new cancer medicines, prices not necessarily linked to health gain and the implications for the sustainability of their healthcare systems.Areas covered: Narrative discussion principally among payers and their advisers regarding potential approaches to the pricing of new cancer medicines.Expert opinion: A number of potential pricing approaches are discussed including minimum effectiveness levels for new cancer medicines, managed entry agreements, multicriteria decision analyses (MCDAs), differential/tiered pricing, fair pricing models, amortization models as well as de-linkage models. We are likely to see a growth in alternative pricing deliberations in view of ongoing challenges. These include the considerable number of new oncology medicines in development including new gene therapies, new oncology medicines being launched with uncertainty regarding their value, and continued high prices coupled with the extent of confidential discounts for reimbursement. However, balanced against the need for new cancer medicines. This will lead to greater scrutiny over the prices of patent oncology medicines as more standard medicines lose their patent, calls for greater transparency as well as new models including amortization models. We will be monitoring these developments.

Identifying Patient Access Barriers for Tumor Necrosis Factor Alpha Inhibitor Treatments in Rheumatoid Arthritis in Five Central Eastern European Countries.

INTRODUCTION: Although there is a significant utilization gap of biologic medicines in the EU, many studies estimate equity in patient access to biopharmaceuticals only based on their availability on the national list of reimbursed medicines. Hidden access barriers may facilitate financial sustainability of pharmaceuticals in less affluent EU countries; however, they have rarely been documented in scientific publications. Our objective was to explore these access barriers for tumor necrosis factor (TNF) alpha inhibitors in rheumatoid arthritis (RA) in five Central and Eastern European countries. METHODS: A detailed interview guide was developed based on multi-stakeholder workshops and a targeted literature review. In each participant country 3-3-3-3 interviews with payers, rheumatologists, patients/patient representatives, and industry representatives were conducted. Responses were aggregated at a country level and validated by primary investigators in each country. RESULTS: Limited number of RA centers and consequently significant travelling time and cost for patients in distant geographical areas, uneven budget allocation among centers, limited capacity of nurses, narrowed patient population in national financial protocols compared to international clinical guidelines in initiating or continuing biologics, high administrative burden in prescribing biologics and limited health literacy of patients were the most relevant barriers to timely patient access in at least three participant countries. CONCLUSION: Assessing only the availability of TNF alpha inhibitors on the national list of reimbursed medicines provides limited information about real-world patient access to these medicines. Revealing hidden access barriers may contribute to initiate policy actions which could reduce inequity in patient access.

Proposal for a regulation on health technology assessment in Europe - opinions of policy makers, payers and academics from the field of HTA.

INTRODUCTION: In January 2018 the European Commission published a Proposal for a Regulation on Health Technology Assessment (HTA): 'Proposal for a Regulation on health technology assessment and amending Directive 2011/24/EU'. A number of stakeholders, including some Member States, welcomed this initiative as it was considered to improve collaboration, reduce duplication and improve efficiency. There were however a number of concerns including its legal basis, the establishment of a single managing authority, the preservation of national jurisdiction over HTA decision-making and the voluntary/mandatory uptake of joint assessments by Member States. Areas covered: This paper presents the consolidated views and considerations on the original Proposal as set by the European Commission of a number of policy makers, payers, experts from pricing and reimbursement authorities and academics from across Europe. Expert commentary: The Proposal has since been extensively discussed at Council and while good progress has been achieved, there are still divergent positions. The European Parliament gave a number of recommendations for amendments. If the Proposal is approved, it is important that a balanced, improved outcome is achieved for all stakeholders. If not approved, the extensive contribution and progress attained should be sustained and preserved, and the best alternative solutions found.

Barriers for Access to New Medicines: Searching for the Balance Between Rising Costs and Limited Budgets.

Introduction: There is continued unmet medical need for new medicines across countries especially for cancer, immunological diseases, and orphan diseases. However, there are growing challenges with funding new medicines at ever increasing prices along with funding increased medicine volumes with the growth in both infectious diseases and non-communicable diseases across countries. This has resulted in the development of new models to better manage the entry of new medicines, new financial models being postulated to finance new medicines as well as strategies to improve prescribing efficiency. However, more needs to be done. Consequently, the primary aim of this paper is to consider potential ways to optimize the use of new medicines balancing rising costs with increasing budgetary pressures to stimulate debate especially from a payer perspective. Methods: A narrative review of pharmaceutical policies and implications, as well as possible developments, based on key publications and initiatives known to the co-authors principally from a health authority perspective. Results: A number of initiatives and approaches have been identified including new models to better manage the entry of new medicines based on three pillars (pre-, peri-, and post-launch activities). Within this, we see the growing role of horizon scanning activities starting up to 36 months before launch, managed entry agreements and post launch follow-up. It is also likely there will be greater scrutiny over the effectiveness and value of new cancer medicines given ever increasing prices. This could include establishing minimum effectiveness targets for premium pricing along with re-evaluating prices as more medicines for cancer lose their patent. There will also be a greater involvement of patients especially with orphan diseases. New initiatives could include a greater role of multicriteria decision analysis, as well as looking at the potential for de-linking research and development from commercial activities to enhance affordability. Conclusion: There are a number of ongoing activities across countries to try and fund new valued medicines whilst attaining or maintaining universal healthcare. Such activities will grow with increasing resource pressures and continued unmet need.

Drug Policy in Slovakia.

Slovak law sets clear rules and timelines in the process of approving the price and reimbursement of drugs. During the last decade, the Ministry of Health adopted several cost-containment measures in the price and reimbursement policy. The most effective measures were the implementation of the external referencing of drug prices in 2008 and the reimbursement law in 2011. The new act introduced several regulations such as making stricter rules for the referencing of prices, setting cost per quality-adjusted life-year threshold, and defining new rules for the setting of reimbursements. On one side, implementation of these measures helped to achieve visible cost savings, but, on the other side, cost-containment policies have had some unintended consequences. In recent years, Slovakia has been facing a decreased availability of drugs because of parallel exports. As a result of the government's effort, Slovakia is the only country in the European Union that implemented a legal ban on the re-export of medicines. During the decade before 2011, many innovative drugs were included in the reimbursement system. Because of stricter legal conditions introduced in 2011, there has been a gradual shift in reimbursing innovative drugs from the standard reimbursement system to reimbursement by way of exceptions of health insurance companies. Recently, there has been an ongoing discussion on possible changes to the reimbursement law.

The Implementation of Managed Entry Agreements in Central and Eastern Europe: Findings and Implications.

BACKGROUND: Managed entry agreements (MEAs) are a set of instruments to facilitate access to new medicines. This study surveyed the implementation of MEAs in Central and Eastern Europe (CEE) where limited comparative information is currently available. METHOD: We conducted a survey on the implementation of MEAs in CEE between January and March 2017. RESULTS: Sixteen countries participated in this study. Across five countries with available data on the number of different MEA instruments implemented, the most common MEAs implemented were confidential discounts (n = 495, 73%), followed by paybacks (n = 92, 14%), price-volume agreements (n = 37, 5%), free doses (n = 25, 4%), bundle and other agreements (n = 19, 3%), and payment by result (n = 10, >1%). Across seven countries with data on MEAs by therapeutic group, the highest number of brand names associated with one or more MEA instruments belonged to the Anatomical Therapeutic Chemical (ATC)-L group, antineoplastic and immunomodulating agents (n = 201, 31%). The second most frequent therapeutic group for MEA implementation was ATC-A, alimentary tract and metabolism (n = 87, 13%), followed by medicines for neurological conditions (n = 83, 13%). CONCLUSIONS: Experience in implementing MEAs varied substantially across the region and there is considerable scope for greater transparency, sharing experiences and mutual learning. European citizens, authorities and industry should ask themselves whether, within publicly funded health systems, confidential discounts can still be tolerated, particularly when it is not clear which country and party they are really benefiting. Furthermore, if MEAs are to improve access, countries should establish clear objectives for their implementation and a monitoring framework to measure their performance, as well as the burden of implementation.

Dabigatran - a continuing exemplar case history demonstrating the need for comprehensive models to optimize the utilization of new drugs.

BACKGROUND: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are effectiveness, safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies showed dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. These concerns resulted in extensive activities pre- to post-launch to manage its introduction. OBJECTIVE: To (i) review authority activities across countries, (ii) use the findings to develop new models to better manage the entry of new drugs, and (iii) review the implications based on post-launch activities. METHODOLOGY: (i) Descriptive review and appraisal of activities regarding dabigatran, (ii) development of guidance for key stakeholder groups through an iterative process, (iii) refining guidance following post launch studies. RESULTS: Plethora of activities to manage dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions and monitoring of prescribing post launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centering on three pillars of pre-, peri-, and post-launch activities. Post-launch activities include increasing use of patient registries to monitor the safety and effectiveness of new drugs in clinical practice. CONCLUSION: Models for introducing new drugs are essential to optimize their prescribing especially where concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding.

Personalizing health care: feasibility and future implications.

Considerable variety in how patients respond to treatments, driven by differences in their geno- and/ or phenotypes, calls for a more tailored approach. This is already happening, and will accelerate with developments in personalized medicine. However, its promise has not always translated into improvements in patient care due to the complexities involved. There are also concerns that advice for tests has been reversed, current tests can be costly, there is fragmentation of funding of care, and companies may seek high prices for new targeted drugs. There is a need to integrate current knowledge from a payer's perspective to provide future guidance. Multiple findings including general considerations; influence of pharmacogenomics on response and toxicity of drug therapies; value of biomarker tests; limitations and costs of tests; and potentially high acquisition costs of new targeted therapies help to give guidance on potential ways forward for all stakeholder groups. Overall, personalized medicine has the potential to revolutionize care. However, current challenges and concerns need to be addressed to enhance its uptake and funding to benefit patients.

Dabigatran - a case history demonstrating the need for comprehensive approaches to optimize the use of new drugs.

BACKGROUND: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies have shown dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. There are also issues with potentially re-designing anticoagulant services. This has resulted in activities across countries to better manage its use. OBJECTIVE: To (i) review authority activities in over 30 countries and regions, (ii) use the findings to develop new models to better manage the entry of new drugs, and (iii) review the implications for all major stakeholder groups. METHODOLOGY: Descriptive review and appraisal of activities regarding dabigatran and the development of guidance for groups through an iterative process. RESULTS: There has been a plethora of activities among authorities to manage the prescribing of dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions, and monitoring of prescribing post-launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centering on three pillars of pre-, peri-, and post-launch activities. CONCLUSION: Models for introducing new drugs are essential to optimize their prescribing especially where there are concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding.

Trends in the lung cancer incidence and mortality in the Slovak and Czech Republics in the contexts of an international comparison.

INTRODUCTION: Lung cancer represents the most frequent cause of cancer-related deaths in the industrialized countries. The aim of this study was to analyze the lung cancer incidence and mortality and the possible reasons for any differences discovered in two neighboring Central European countries-the Slovak Republic. METHODS: We used linear regression model when analyzing incidence and mortality; the trends are presented with corresponding 95% confidence intervals (CI) and p-value with null hypothesis being constant with time. RESULTS: Statistically significant increase of age-standardized incidence (0.707/100,000/year, 95% CI 0.107-1.307, p = 0,025) and mortality (1.339/100,000/year, 95% CI 1.050-1.629, p < 0.0001) of the lung cancer was revealed in males in the Slovak Republic (1980-1991). On the contrary, values of both indicators were stabilized in the Czech Republic. Since year 1991-2005 a statistically highly significant decrease of both incidence and mortality values was observed in males, which was greater in the Slovak Republic. Peak of the curve was not reached in women population, while incidence and mortality values have significantly continuous growth in both countries. CONCLUSIONS: According to the lung cancer incidence and mortality trends in both countries (in correlation with smoking prevalence) we consider the support of efforts to change the attitude towards smoking predominantly in women and younger generation to be the most accurate action to reduce these trends.

Health care reform in six Central European countries. A focus on health economic requirements in the drug pricing and reimbursement processes.

This study gives an overview of the health care reform in six Central European countries after the transition from a central planning system to a regulated market economy. We focused on cost containment policies for drugs, especially the requirements for submitting health economic data in the pricing and/or reimbursement processes. The literature review was supplemented with a survey with decision makers at national health authorities in each country. The study covered Croatia, Czech Republic, Hungary, Poland, Slovakia, and Slovenia. All countries had in common that health economic information was used in reimbursement rather than in pricing processes. Differences between the six countries were mainly variations in the relative importance of health economic data and the presence of explicit requirements and guidelines. Published health economic guidelines exist in two countries and one of the six countries applies a mandatory submission system for a selected range of new drugs. In most of the Central European countries it is more typical that authorities issue a brief list of required data for reimbursement submissions that include health economic information among other data. There is a generally widespread expectation towards more systematic and formalized requirements for health economic and outcomes research data appearing within the next 3-5 years in the region.