Patients, payers and developers of Orphan Medicinal Products: lessons learned from 10 years' multi-stakeholder dialogue on improving access in Europe via MoCA.

BACKGROUND: The Mechanism of Coordinated Access to Orphan Medicinal Products (MoCA) was established in 2013 with the intention of developing a coordinated mechanism between volunteering EU stakeholders and developers of Orphan Medicinal Products (OMPs) to support the exchange of information aimed at enabling informed decisions on pricing and reimbursement at Member State level and to evaluate the value of an OMP based on a Transparent Value Framework. The objective of the collaborative approach was to support more equitable access to authorised therapies for people living with rare diseases, rational prices for payers and more predictable market conditions for OMP developers. Over the past 10 years, the MoCA has conducted a series of pilot projects, examining a variety of different products and technologies at different stages of development; and with contributions from a variety of patient representatives, participation from EU payers from a range of Member States and, recently, with EUnetHTA members and the European Medicines Agency participating in the meetings as observers. RESULTS: 10 years on from the establishment of the MoCA, the European landscape has significantly evolved, not only in the field of drug development with increasingly transformative therapies based on novel technologies, but also in terms of larger numbers of approved treatments, increased budget impact and the resulting associated uncertainties; as well as in terms of stakeholder collaboration and interactions. The value of early dialogue with OMP developers, including the EU payer community via their national decision-making authorities, is a key element within this early interaction and contributes to identifying, managing and reducing uncertainties allowing a prospectively planned approach earlier in development and, consequently, to support more timely, sustainable and equitable access to new OMPs, particularly where there is a high unmet medical need. CONCLUSIONS: The voluntary, informal nature of the MoCA interactions creates a flexible framework for non-binding dialogue. A forum for such interactions is needed to achieve the aims of the MoCA and both to support healthcare systems in planning as well as to underpin timely, equitable and sustainable access to new therapies for patients with rare diseases within the EU.

Assessing the Accuracy of Sales Forecasts Submitted by Pharmaceutical Companies Applying for Reimbursement in Austria.

Objectives: Reimbursement decisions on new medicines require an assessment of their value. In Austria, when applying for reimbursement of new medicines, pharmaceutical companies are also obliged to submit forecasts of future sales. We systematically examined the accuracy of these pharmaceutical sales forecasts and hence the usefulness of these forecasts for reimbursement evaluations. Methods: We retrospectively analyzed reimbursement applications of 102 new drugs submitted between 2005 and 2014, which were accepted for reimbursement outside of hospitals, and for which actual reimbursed sales were available for at least 3 years. The main outcome variable was the accuracy ratio, defined as the ratio of forecasted sales submitted by pharmaceutical companies when applying for reimbursement to actual sales from reimbursement data. Results: The median accuracy ratio [95% confidence interval] was 1.33 [1.03; 1.74, range 0.15-37.5], corresponding to a median overestimation of actual sales by 33%. Forecasts of actual sales for 55.9% of all examined products either overestimated actual sales by more than 100% or underestimated them by more than 50%. The accuracy of sales forecasts did not show systematic change over the analyzed decade nor was it discernibly influenced by reimbursement status (restricted or unrestricted), the degree of therapeutic benefit, or the therapeutic area of the pharmaceutical product. Sales forecasts of drugs with a higher degree of innovation and those within a dynamic market tended to be slightly more accurate. Conclusions: The majority of sales forecasts provided by applicants for reimbursement evaluations in Austria were highly inaccurate and were on average too optimistic. This is in line with published results for other jurisdictions and highlights the need for caution when using such forecasts for reimbursement procedures.

Comparative effectiveness of branded vs. generic versions of antihypertensive, lipid-lowering and hypoglycemic substances: a population-wide cohort study.

Generic medications offer substantial potential cost savings to health systems compared to their branded counterparts. In Europe and the US, they are only approved if they are bioequivalent to the respective originator product. Nevertheless, the lack of clinical outcomes is sometimes used as the reason for hesitancy in prescribing generics. We performed an observational retrospective study on 17 branded vs. generic pharmaceutical substances for the treatment of hypertension/heart failure, hyperlipidemia, and diabetes mellitus in a dataset of 9,413,620 insured persons, representing nearly the full population of Austria, from 2007 to 2012. We compared generic vs. branded medications using hazard ratios for all-cause death and major adverse cardiac and cardiovascular events (MACCE) as outcomes of interest. Using patient demographics, health characteristics from hospitalization records, and pharmacy records as covariates, we controlled for confounding in Cox models through inverse probability of treatment weighting (IPTW) using high-dimensional propensity scores. We observed that the unadjusted hazard ratios strongly favor generic drugs for all three pooled treatment indications (hypertension/heart failure, hyperlipidemia, diabetes mellitus), but were attenuated towards unity with increasingly larger covariate sets used for confounding control. We found that after IPTW adjustment the generic formulation was associated with significantly fewer deaths in 10 of 17 investigated drugs, and with fewer MACCE in 11 of 17 investigated drugs. This result favoring generic drugs was also present in a number of sub-analyses based on gender, prior disease status, and treatment discontinuation. E-value sensitivity analyses suggested that only strong unmeasured confounding could fully explain away the observed results. In conclusion, generic medications were at least similar, and in some cases superior, to their branded counterparts regarding mortality and major cardiovascular events.

Achieving equal and timely access to innovative anticancer drugs in the European Union (EU): summary of a multidisciplinary CECOG-driven roundtable discussion with a focus on Eastern and South-Eastern EU countries.

The Central European Cooperative Oncology Group (CECOG) and 'ESMO Open-Cancer Horizons' roundtable discussion brought together stakeholders from several European Union (EU) countries involved in drug development, drug authorisation and reimbursement or otherwise affected by delayed and unequal access to innovative anticancer drugs. The approval process of drugs is well established and access delays can be caused directly or indirectly by national or regional decision-making processes on reimbursement. The two key aspects for those involved in reimbursement decisions are first the level of evidence required to decide and second pricing, which can be challenging for some innovative oncology compounds, especially in Eastern and South-Eastern European countries. Other important factors include: available healthcare budget; the structure and sophistication of healthcare authorities and health technology assessment processes; societal context and political will. From the point of view of the pharmaceutical industry, better alignment between stakeholders in the process and adaptive pathway initiatives is desirable. Key aspects for patients are improved access to clinical trials, preapproval availability and reports on real-world evidence. Restricted access limits oncologists' daily work in Eastern and South-Eastern EU countries. The roundtable discussion suggested considering the sequencing of regulatory approval and reimbursement decisions together with more flexible contracting as a possible way forward. The panel concluded that early and regular dialogue between all stakeholders including regulators, payers, patient stakeholders and industry is required to improve the situation.

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.

HTA programme response to the challenges of dealing with orphan medicinal products: Process evaluation in selected European countries.

BACKGROUND: Challenges commonly encountered in HTA of orphan medicinal products (OMPs) were identified in Advance-HTA. Since then, new initiatives have been developed to specifically address issues related to HTA of OMPs. OBJECTIVE AND METHODS: This study aimed to understand why these new HTA initiatives in England, Scotland and at European-level were established and whether they resolve the challenges of OMPs. The work of Advance-HTA was updated with a literature review and a conceptual framework of clinical, regulatory and economic challenges for OMPs was developed. The new HTA programmes were critiqued against the conceptual framework and outstanding challenges identified. RESULTS: The new programmes in England and Scotland recognise the challenges identified in demonstrating the value of ultra-OMPs (and OMPs) and that they require a different process to standard HTA approaches. Wider considerations of disease and treatment experiences from a multi-stakeholder standpoint are needed, combined with other measures to deal with uncertainty (e.g. managed entry agreements). While approaches to assessing this new view of value of OMPs, extending beyond cost/QALY frameworks, differ, their criteria are similar. These are complemented by a European initiative that fosters multi-stakeholder dialogue and consensus about value determinants throughout the life-cycle of an OMP. CONCLUSION: New HTA programmes specific to OMPs have been developed but questions remain about whether they sufficiently capture value and manage uncertainty in clinical practice.

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.

The European challenges of funding orphan medicinal products.

BACKGROUND: Funding of orphan medicinal products (OMPs) is an increasing challenge in the European Union (EU). OBJECTIVES: To identify the different methods for public funding of OMPs in order to map the availability for rare disease patients, as well as to compare the public expenditures on OMPs in 8 EU member states. METHODS: Information on the reimbursement status of 83 OMPs was collected in 8 countries by distinguishing standard and special reimbursements. In two consecutive years, the total public expenditures on OMPs were calculated by using annual EUR exchange rates. Annual total public expenditures were calculated per capita, and as a proportion of GDP, total public pharmaceutical and healthcare budgets. Differences between countries were compared by calculating the deviations from the average spending of countries. RESULTS: In 2015 29.4-92.8% of the 83 OMPs were available with any kind of public reimbursement in participant countries including special reimbursement on an individual basis. In Austria, Belgium and France more OMPs were accessible for patients with public reimbursement than in Bulgaria, Czech Republic, Hungary and Poland. Standard reimbursement through retail pharmacies and/or hospitals was applied from 0 to 41% of OMPs. The average annual total public expenditure ranged between 1.4-23.5 €/capita in 2013 and 2014. Higher income countries spent more OMPs in absolute terms. Participant countries spent 0.018-0.066% of their GDPs on funding OMPs. Average expenditures on OMPs were ranged between 2.25-6.51% of the public pharmaceutical budget, and 0.44-0.96% of public healthcare expenditures. CONCLUSIONS: Standard and special reimbursement techniques play different roles in participant countries. The number of accessible OMPs indicated an equity gap between Eastern and Western Europe. The spending on OMPs as a proportion of GDP, public pharmaceutical and healthcare expenditure was not higher in lower income countries, which indicates substantial differences in patient access to OMPs in favour of higher-income countries. Equity in access for patients with rare diseases is an important policy objective in each member state of the EU; however, equity in access should be harmonized at the European level.

Adaptive Pathways: Possible Next Steps for Payers in Preparation for Their Potential Implementation.

Medicines receiving a conditional marketing authorization through Medicines Adaptive Pathways to Patients (MAPPs) will be a challenge for payers. The "introduction" of MAPPs is already seen by the European Medicines Agency (EMA) as a fait accompli, with payers not consulted or involved. However, once medicines are approved through MAPPs, they will be evaluated for funding by payers through different activities. These include Health Technology Assessment (HTA) with often immature clinical data and high uncertainty, financial considerations, and negotiations through different types of agreements, which can require monitoring post launch. Payers have experience with new medicines approved through conditional approval, and the fact that MAPPs present additional challenges is a concern from their perspective. There may be some activities where payers can collaborate. The final decisions on whether to reimburse a new medicine via MAPPs will have more variation than for medicines licensed via conventional processes. This is due not only to increasing uncertainty associated with medicines authorized through MAPPs but also differences in legal frameworks between member states. Moreover, if the financial and side-effect burden from the period of conditional approval until granting full marketing authorization is shifted to the post-authorization phase, payers may have to bear such burdens. Collection of robust data during routine clinical use is challenging along with high prices for new medicines during data collection. This paper presents the concept of MAPPs and possible challenges. Concerns and potential ways forward are discussed and a number of recommendations are presented from the perspective of payers.

Systemic Measures and Legislative and Organizational Frameworks Aimed at Preventing or Mitigating Drug Shortages in 28 European and Western Asian Countries.

Drug shortages have been identified as a public health problem in an increasing number of countries. This can negatively impact on the quality and efficiency of patient care, as well as contribute to increases in the cost of treatment and the workload of health care providers. Shortages also raise ethical and political issues. The scientific evidence on drug shortages is still scarce, but many lessons can be drawn from cross-country analyses. The objective of this study was to characterize, compare, and evaluate the current systemic measures and legislative and organizational frameworks aimed at preventing or mitigating drug shortages within health care systems across a range of European and Western Asian countries. The study design was retrospective, cross-sectional, descriptive, and observational. Information was gathered through a survey distributed among senior personnel from ministries of health, state medicines agencies, local health authorities, other health or pharmaceutical pricing and reimbursement authorities, health insurance companies and academic institutions, with knowledge of the pharmaceutical markets in the 28 countries studied. Our study found that formal definitions of drug shortages currently exist in only a few countries. The characteristics of drug shortages, including their assortment, duration, frequency, and dynamics, were found to be variable and sometimes difficult to assess. Numerous information hubs were identified. Providing public access to information on drug shortages to the maximum possible extent is a prerequisite for performing more advanced studies on the problem and identifying solutions. Imposing public service obligations, providing the formal possibility to prescribe unlicensed medicines, and temporary bans on parallel exports are widespread measures. A positive finding of our study was the identification of numerous bottom-up initiatives and organizational frameworks aimed at preventing or mitigating drug shortages. The experiences and lessons drawn from these initiatives should be carefully evaluated, monitored, and presented to a wider international audience for careful appraisal. To be able to find solutions to the problem of drug shortages, there is an urgent need to develop a set of agreed definitions for drug shortages, as well as methodologies for their evaluation and monitoring. This is being progressed.

Payers' Views of the Changes Arising through the Possible Adoption of Adaptive Pathways.

Payers are a major stakeholder in any considerations and initiatives concerning adaptive licensing of new medicinal products, also referred to as Medicines Adaptive Pathways to patients (MAPPs). Firstly, the scope and necessity of MAPPs need further scrutiny, especially with regard to the definition of unmet need. Conditional approval pathways already exist for new medicines for seriously debilitating or life-threatening diseases and only a limited number of new medicines are innovative. Secondly, MAPPs will result in new medicines on the market with limited evidence about their effectiveness and safety. Additional data are to be collected after approval. Consequently, adaptive pathways may increase the risk of exposing patients to ineffective or unsafe medicines. We have already seen medicines approved conventionally that subsequently proved ineffective or unsafe amongst a wider, more co-morbid population as well as medicines that could have been considered for approval under MAPPs but subsequently proved ineffective or unsafe in Phase III trials and were never licensed. Thirdly, MAPPs also put high demands on payers. Routine collection of patient level data is difficult with high transaction costs. It is not clear who will fund these. Other challenges for payers include shifts in the risk governance framework, implications for evaluation and HTA, increased complexity of setting prices, difficulty with ensuring equity in the allocation of resources, definition of responsibility and liability and implementation of stratified use. Exit strategies also need to be agreed in advance, including price reductions, rebates, or reimbursement withdrawals when price premiums are not justified. These issues and concerns will be discussed in detail including potential ways forward.

Introduction and Utilization of High Priced HCV Medicines across Europe; Implications for the Future.

BACKGROUND: Infection with the Hepatitis C Virus (HCV) is a widespread transmittable disease with a diagnosed prevalence of 2.0%. Fortunately, it is now curable in most patients. Sales of medicines to treat HCV infection grew 2.7% per year between 2004 and 2011, enhanced by the launch of the protease inhibitors (PIs) boceprevir (BCV) and telaprevir (TVR) in addition to ribavirin and pegylated interferon (pegIFN). Costs will continue to rise with new treatments including sofosbuvir, which now include interferon free regimens. OBJECTIVE: Assess the uptake of BCV and TVR across Europe from a health authority perspective to offer future guidance on dealing with new high cost medicines. METHODS: Cross-sectional descriptive study of medicines to treat HCV (pegIFN, ribavirin, BCV and TVR) among European countries from 2008 to 2013. Utilization measured in defined daily doses (DDDs)/1000 patients/quarter (DIQs) and expenditure in Euros/DDD. Health authority activities to influence treatments categorized using the 4E methodology (Education, Engineering, Economics and Enforcement). RESULTS: Similar uptake of BCV and TVR among European countries and regions, ranging from 0.5 DIQ in Denmark, Netherlands and Slovenia to 1.5 DIQ in Tayside and Catalonia in 2013. However, different utilization of the new PIs vs. ribavirin indicates differences in dual vs. triple therapy, which is down to factors including physician preference and genotypes. Reimbursed prices for BCV and TVR were comparable across countries. CONCLUSION: There was reasonable consistency in the utilization of BCV and TVR among European countries in comparison with other high priced medicines. This may reflect the social demand to limit the transmission of HCV. However, the situation is changing with new curative medicines for HCV genotype 1 (GT1) with potentially an appreciable budget impact. These concerns have resulted in different prices across countries, with their impact on budgets and patient outcomes monitored in the future to provide additional guidance.

LOOKING BACK ON 5 YEARS OF HORIZON SCANNING IN ONCOLOGY.

OBJECTIVES: The regularly structured adaptation of health technology assessment (HTA) programs is of utmost importance to sustain the relevance of the products for stakeholders and to justify investment of scarce financial resources. This study describes internal adjustments and external measures taken to ensure the Horizon Scanning Programme in Oncology (HSO) is current. METHODS: Formal evaluation methods comprising a survey, a download, an environmental analysis, and a Web site questionnaire were used to evaluate user satisfaction. RESULTS: The evaluation showed that users were satisfied with HSO outputs in terms of timeliness, topics selected, and depth of information provided. Discussion of these findings with an expert panel led to changes such as an improved dissemination strategy and the introduction of an additional output, that is, the publication of a league table of emerging oncology drugs. The rather high level of international usage and the environmental analysis highlighted a considerable overlap in topics assessed and, thus, the potential for international collaboration. As a consequence, thirteen reports were jointly published based on eleven "calls for collaboration." To further facilitate collaboration and the usability of reports for other agencies, HSO reports will be adjusted according to tools developed at a European level. CONCLUSIONS: Evaluation of the impact of HTA programs allows the tailoring of outputs to fit the needs of the target population. However, within a fast developing HTA community, estimates of impact will increasingly be determined by international collaborative efforts. Refined methods and a broader definition of impact are needed to ultimately capture the efficiency of national HTA programs.

Prevalence and determinants of unintended double medication of antihypertensive, lipid-lowering, and hypoglycemic drugs in Austria: a nationwide cohort study.

PURPOSE: Double medication is defined as the unintended overlapping prescription of two identical substances with the same route of administration by two different prescribers to the same patient. Consequences of double medication are reduced patient safety and excess healthcare costs. Based on nationwide prescription data from 2011 covering 97% of Austria's population, we estimated double medication prevalences for treatment of hypertension, hyperlipidemia, and diabetes mellitus. METHODS: We investigated prescriptions of 88 antihypertensive, 16 lipid-lowering and 29 hypoglycemic substances in 7,971,323 persons in 2011. Prevalence of double medication was calculated patientwise (prevalence by patients) and timewise (prevalence by patient-years). Risk factors for double medication were identified by logistic regression. RESULTS: For antihypertensive, lipid-lowering, and hypoglycemic subtances, overall 15.0% (men: 15.1%, women: 15.0%), 13.1% (13.7%, 12.5%), and 13.0% (13.0%, 13.4%) of patients were doubly medicated, respectively. Corresponding prevalences by patient-years were 1.6%, 2.0%, and 1.2%. Logistic regression confirmed lower age and copayment waiver as independent risk factors of double medication. Furthermore, double medication occurred more often with prescriptions from hospitals or internal medicine specialists compared with general practitioners, as well as in August compared with earlier or later in the calendar year. CONCLUSION: While appropriate care or comanagement of patients by internal medicine specialists and general practitioners may explain some of the double prescriptions, our data indicate that unintended double medication is frequent. In Austria, lack of financial incentives of patients to avoid filling duplicate prescriptions explains a considerable fraction of double medication occurrences.

European collaboration on relative effectiveness assessments: What is needed to be successful?

OBJECTIVE: The objective of this study is to identify the possible barriers and critical success factors for the implementation of European collaboration in the field of relative effectiveness assessment (REA) of drugs. METHODS: Data were gathered through semi-structured interviews with representatives from eight European health technology assessment (HTA) organisations involved in assessment of drugs for coverage decision-making (AAZ, AIFA, AHTAPol, HAS, HVB, IQWIG, NICE and ZiN). RESULTS: Potential barriers identified mainly relate to methodology, resources and challenges with implementation in the respective national processes (e.g. legal restrictions). The most critical success factors for production of cross-border assessments were the continuous cooperation of competent partners, and the quality and timely availability of the assessment. CONCLUSION: Further adaptation of the process and methods is required for optimal collaboration. In the near future it can be expected that cross-border assessments will meet in particular the needs of smaller/middle-sized European countries and also European countries with less developed HTA systems as the potential efficiency/quality gains are the highest for these countries. Therefore, national implementation of cross-border assessments is especially likely in these countries in the coming years. Once more experience is gained with cross-border assessments, and successes become more evident, efficiency/quality gains may also be likely for some larger countries with well established processes.

Potential savings in prescription drug costs for hypertension, hyperlipidemia, and diabetes mellitus by equivalent drug substitution in Austria: a nationwide cohort study.

BACKGROUND: Healthcare systems spend considerable proportions of their budgets on pharmaceutical treatment of hypertension, hyperlipidemia, and diabetes mellitus. From data on almost all residents of Austria, a country with mandatory health insurance and universal health coverage, we estimated potential cost savings by substituting prescribed medicines with the cheapest medicines that were of the same chemical substance and strength, and available during the same time. METHODS: Data from 8.3 million persons (98.5 % of the total Austrian insured population) from 2009-2012 were analyzed. Real prescription costs for antihypertensive, lipid-lowering, and hypoglycemic medicines achievable by same-substance, same-strength drug substitution were computed for each active ingredient, and per gender and 1-year age category of patients. RESULTS: In 2012, health insurance providers spent 231.3 million, 77.8 million, and 91.9 million for antihypertensive, lipid-lowering, and diabetes medications, of which 52.2 million (22.6 %), 15.9 million (20.5 %), and 4.1 million (4.5 %), respectively, could have been saved by same-substance drug substitution. Highest potential savings were calculated for amlodipine (8.0 million, 65.4 %), simvastatin (12.2 million, 59.3 %), and metformin (2.4 million, 54.6 %), respectively. Higher savings for men than for women resulted from differing prescribed cumulative dosages and proportions of patients with co-payment waiver. Potential cost savings in antihypertensive and lipid-lowering drugs increased from 2009-2012. CONCLUSION: Our study highlights the cost-savings potential from arguably the most acceptable of interventions, simply switching to the cheapest available same-substance, same-strength product. In 2012, this strategy could have reduced costs for antihypertensive, lipid-lowering, and hypoglycemic treatment by up to 18.0 %.

Are new models needed to optimize the utilization of new medicines to sustain healthcare systems?

Medicines have made an appreciable contribution to improving health. However, even high-income countries are struggling to fund new premium-priced medicines. This will grow necessitating the development of new models to optimize their use. The objective is to review case histories among health authorities to improve the utilization and expenditure on new medicines. Subsequently, use these to develop exemplar models and outline their implications. A number of issues and challenges were identified from the case histories. These included the low number of new medicines seen as innovative alongside increasing requested prices for their reimbursement, especially for oncology, orphan diseases, diabetes and HCV. Proposed models center on the three pillars of pre-, peri- and post-launch including critical drug evaluation, as well as multi-criteria models for valuing medicines for orphan diseases alongside potentially capping pharmaceutical expenditure. In conclusion, the proposed models involving all key stakeholder groups are critical for the sustainability of healthcare systems or enhancing universal access. The models should help stimulate debate as well as restore trust between key stakeholder groups.

Different initiatives across Europe to enhance losartan utilization post generics: impact and implications.

INTRODUCTION: There is an urgent need for health authorities across Europe to fully realize potential savings from increased use of generics to sustain their healthcare systems. A variety of strategies were used across Europe following the availability of generic losartan, the first angiotensin receptor blocker (ARB) to be approved and marketed, to enhance its prescribing vs. single-sourced drugs in the class. Demand-side strategies ranged from 100% co-payment for single-sourced ARBs in Denmark to no specific measures. We hypothesized this heterogeneity of approaches would provide opportunities to explore prescribing in a class following patent expiry. OBJECTIVE: Contrast the impact of the different approaches among European countries and regions to the availability of generic losartan to provide future guidance. METHODOLOGY: Retrospective segmented regression analyses applying linear random coefficient models with country specific intercepts and slopes were used to assess the impact of the various initiatives across Europe following the availability of generic losartan. Utilization measured in defined daily doses (DDDs). Price reductions for generic losartan were also measured. RESULTS: Utilization of losartan was over 90% of all ARBs in Denmark by the study end. Multiple measures in Sweden and one English primary care group also appreciably enhanced losartan utilization. Losartan utilization actually fell in some countries with no specific demand-side measures. Considerable differences were seen in the prices of generic losartan. CONCLUSION: Delisting single-sourced ARBs produced the greatest increase in losartan utilization. Overall, multiple demand-side measures are needed to change physician prescribing habits to fully realize savings from generics. There is no apparent "spill over" effect from one class to another to influence future prescribing patterns even if these are closely related.

Multiple policies to enhance prescribing efficiency for established medicines in Europe with a particular focus on demand-side measures: findings and future implications.

INTRODUCTION: The appreciable growth in pharmaceutical expenditure has resulted in multiple initiatives across Europe to lower generic prices and enhance their utilization. However, considerable variation in their use and prices. OBJECTIVE: Assess the influence of multiple supply and demand-side initiatives across Europe for established medicines to enhance prescribing efficiency before a decision to prescribe a particular medicine. Subsequently utilize the findings to suggest potential future initiatives that countries could consider. METHOD: An analysis of different methodologies involving cross national and single country retrospective observational studies on reimbursed use and expenditure of PPIs, statins, and renin-angiotensin inhibitor drugs among European countries. RESULTS: Nature and intensity of the various initiatives appreciably influenced prescribing behavior and expenditure, e.g., multiple measures resulted in reimbursed expenditure for PPIs in Scotland in 2010 56% below 2001 levels despite a 3-fold increase in utilization and in the Netherlands, PPI expenditure fell by 58% in 2010 vs. 2000 despite a 3-fold increase in utilization. A similar picture was seen with prescribing restrictions, i.e., (i) more aggressive follow-up of prescribing restrictions for patented statins and ARBs resulted in a greater reduction in the utilization of patented statins in Austria vs. Norway and lower utilization of patented ARBs vs. generic ACEIs in Croatia than Austria. However, limited impact of restrictions on esomeprazole in Norway with the first prescription or recommendation in hospital where restrictions do not apply. Similar findings when generic losartan became available in Western Europe. CONCLUSIONS: Multiple demand-side measures are needed to influence prescribing patterns. When combined with supply-side measures, activities can realize appreciable savings. Health authorities cannot rely on a "spill over" effect between classes to affect changes in prescribing.