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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.

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.MAPPs will result in new medicines initially 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 considered for approval under MAPPs but subsequently proved ineffective or unsafe in Phase III trials and were never licensed. 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 allocation of resources, 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.

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. Utilisation measured in defined daily doses (DDDs)/ 1000 patients/ quarter (DIQs) and expenditure in Euros/ DDD. Health authority activities to influence treatments categorised 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 utilisation of the new PIs versus ribavirin indicates differences in dual versus 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 utilisation 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 negotiations across countries, with their impact monitored in the future to provide additional guidance.

Background: Rising expenditure for new cancer medicines is accelerating concerns that their costs will become unsustainable for universal healthcare access. Moreover, early market access of new oncology medicines lacking appropriate clinical evaluation generates uncertainty over their cost-effectiveness and increases expenditure for unknown health gain. Patient-level data can complement clinical trials and generate better evidence on the effectiveness, safety and outcomes of these new medicines in routine care. This can support policy decisions including funding. Consequently, there is a need for improving datasets for establishing real-world outcomes of newly launched oncology medicines.Aim: To outline the types of available datasets for collecting patient-level data for oncology among different European countries. Additionally, to highlight concerns regarding the use and availability of such data from a health authority perspective as well as possibilities for cross-national collaboration to improve data collection and inform decision-making.Methods: A mixed methods approach was undertaken through a cross-sectional questionnaire followed-up by a focus group discussion. Participants were selected by purposive sampling to represent stakeholders across different European countries and healthcare settings. Descriptive statistics were used to analyze quantifiable questions, whilst content analysis was employed for open-ended questions.Results: 25 respondents across 18 European countries provided their insights on the types of datasets collecting oncology data, including hospital records, cancer, prescription and medicine registers. The most available is expenditure data whilst data concerning effectiveness, safety and outcomes is less available, and there are concerns with data validity. A major constraint to data collection is the lack of comprehensive registries and limited data on effectiveness, safety and outcomes of new medicines. Data ownership limits data accessibility as well as possibilities for linkage, and data collection is time-consuming, necessitating dedicated staff and better systems to facilitate the process. Cross-national collaboration is challenging but the engagement of multiple stakeholders is a key step to reach common goals through research.Conclusion: This study acts as a starting point for future research on patient-level databases for oncology across Europe. Future recommendations will require continued engagement in research, building on current initiatives and involving multiple stakeholders to establish guidelines and commitments for transparency and data sharing.

Background: In last 2 decades, there have been substantial changes in the utilization patterns of antihypertensive medicines following new clinical trials and the introduction of new treatment guidelines. The aim of this study was to analyze utilization and prescribing patterns regarding antihypertensive medicines in the Republic of Srpska, Bosnia and Herzegovina during an 11-years follow-up according to national and European treatment guidelines.Methods: In this retrospective, observational study, medicine utilization data were analyzed between 2009–2019 period using the ATC/DDD methodology and expressed as the number of DDD/1,000 inhabitants/day (DID/TID). The medicine utilization 90% (DU90%) method was used for determine the quality of prescribing.Results: During the observed period, the use of antihypertensive medicines increased more than 3-times (125.97 DDD/TID in 2009 vs 414.95 DDD/TID in 2019), corresponding to a rise in the prevalence of hypertensive patients from 91.7/1,000 to 186.3/1,000 in the same period. This was mainly driven by increased use of angiotensin converting enzyme inhibitors with 241.69%, beta blockers with 146.87%, calcium channel blockers with 251.55%, and diuretics with 178.95%. Angiotensin receptor blockers were the fastest growing group of antihypertensive medicines in this period and their utilization increased nearly 40 times.Conclusions: The overall antihypertensive medicines utilization was largely influenced by national and ESH/ESC guidelines and strongly corresponded to the positive medicine list of the national health insurance fund. Antihypertensive medicines utilization is comparable with medicine utilization trends in other countries.

Background: From October 2018, adalimumab biosimilars could enter the European market. However, in some countries, such as Netherlands, high discounts reported for the originator product may have influenced biosimilar entry.Objectives: The aim of this paper is to provide a European overview of (list) prices of originator adalimumab, before and after loss of exclusivity; to report changes in the reimbursement status of adalimumab products; and discuss relevant policy measures.Methods: Experts in European countries received a survey consisting of three parts: 1) general financing/co-payment of medicines, 2) reimbursement status and prices of originator adalimumab, and availability of biosimilars, and 3) policy measures related to the use of adalimumab.Results: In May 2019, adalimumab biosimilars were available in 24 of the 30 countries surveyed. Following introduction of adalimumab biosimilars, a number of countries have made changes in relation to the reimbursement status of adalimumab products. Originator adalimumab list prices varied between countries by a factor of 2.8 before and 4.1 after loss of exclusivity. Overall, list prices of originator adalimumab decreased after loss of exclusivity, although for 13 countries list prices were unchanged. When reported, discounts/rebates on originator adalimumab after loss of exclusivity ranged from 0% to approximately 26% (Romania), 60% (Poland), 80% (Denmark, Italy, Norway), and 80–90% (Netherlands), leading to actual prices per pen or syringe between €412 (Finland) and €50 – €99 (Netherlands). To leverage competition following entry of biosimilar adalimumab, only a few countries adopted measures specifically for adalimumab in addition to general policies regarding biosimilars. In some countries, a strategy was implemented even before loss of exclusivity (Denmark, Scotland), while others did not report specific measures.Conclusion: Even though originator adalimumab is the highest selling product in the world, few countries have implemented specific policies and practices for (biosimilar) adalimumab. Countries with biosimilars on the market seem to have competition lowering list or actual prices. Reported discounts varied widely between countries.

Introduction: There are increasing concerns world-wide with growing rates of antibiotic resistance necessitating urgent action. There have been a number of initiatives in the Republic of Srpska in recent years to address this and improve rational antibiotic prescribing and dispensing despite limited resources to fund multiple initiatives.Objective: Analyse antibiotic utilization patterns in the Republic of Srpska following these multiple initiatives as a basis for developing future programmes in the Republic if needed.Methods: Observational retrospective study of total outpatient antibiotic utilization from 2010 to 2015, based on data obtained from the Public Health Institute, alongside documentation of ongoing initiatives to influence utilization. The quality of antibiotic utilization principally assessed according to ESAC, ECDC, and WHO quality indicators and DU 90% (the drug utilization 90%) profile as well as vs. neighboring countries.Results: Following multiple initiatives, antibiotic utilization remained relatively stable in the Republic at 15.6 to 18.4 DIDs, with a decreasing trend in recent years, with rates comparable or lower than neighboring countries. Amoxicillin and the penicillins accounted for 29–40 and 50% of total utilization, respectively. Overall, limited utilization of co-amoxiclav (7–11%), cephalosporins, macrolides, and quinolones, as well as low use of third and fourth generation cephalosporins vs. first and second cephalosporins. However, increasing utilization of co-amoxiclav and azithromycin, as well as higher rates of quinolone utilization compared to some countries, was seen.Conclusions: Multiple interventions in the Republic of Srpska in recent years have resulted in one of the lowest utilization of antibiotics when compared with similar countries, acting as an exemplar to others. However, there are some concerns with current utilization of co-amoxiclav and azithromycin which are being addressed. This will be the subject of future research activities.

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.