Hanne Bak Pedersen

Antibiotic use in eastern Europe: a cross-national database study in coordination with the WHO Regional Office for Europe

BACKGROUND There are no reliable data on antibiotic use in non-European Union (EU) southern and eastern European countries and newly independent states. We aimed to collect valid, representative, comparable data on systemic antimicrobial use in these non-EU countries of the WHO European region. METHODS Validated 2011 total national wholesale antibiotic-use data of six southern and eastern European countries and regions and seven newly independent states were analysed in accordance with the WHO anatomical therapeutic chemical (ATC)/defined daily doses (DDD) method and expressed in DDD/1000 inhabitants per day (DID). FINDINGS Total (outpatients and hospital care) antibiotic use ranged from 15·3 DID for Armenia to 42·3 DID for Turkey. Co-amoxiclav was mainly used in Georgia (42·9% of total antibiotic use) and Turkey (30·7%). Newly independent states used substantial quantities of ampicillin and amoxicillin (up to 55·9% of total antibiotic use in Azerbaijan). Montenegro and Serbia were the highest consumers of macrolides (15·8% and 19·5% of total antibiotic use, respectively), mainly azithromycin. Parenteral antibiotic treatment is common practice: 46·4% of total antibiotic use in Azerbaijan (mainly ampicillin; 5·3 DID) and 31·1% of total antibiotic use in Tajikistan (mainly ceftriaxone; 4·7 DID). INTERPRETATION This study provides publicly available total antibiotic-use data for 13 non-EU countries and areas of the WHO European region. These data will raise awareness of inappropriate antibiotic use and stimulate policy makers to develop action plans. The established surveillance system provides a method to develop quality indicators of antibiotic use and to assess the effect of policy and regulatory actions. FUNDING Netherlands Ministry of Health, Welfare, and Sport, and EU.

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.

Exploring the evidence base for national and regional policy interventions to combat resistance

The effectiveness of existing policies to control antimicrobial resistance is not yet fully understood. A strengthened evidence base is needed to inform effective policy interventions across countries with different income levels and the human health and animal sectors. We examine three policy domains-responsible use, surveillance, and infection prevention and control-and consider which will be the most effective at national and regional levels. Many complexities exist in the implementation of such policies across sectors and in varying political and regulatory environments. Therefore, we make recommendations for policy action, calling for comprehensive policy assessments, using standardised frameworks, of cost-effectiveness and generalisability. Such assessments are especially important in low-income and middle-income countries, and in the animal and environmental sectors. We also advocate a One Health approach that will enable the development of sensitive policies, accommodating the needs of each sector involved, and addressing concerns of specific countries and regions.

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.

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.

Quality indicators as a tool in improving the introduction of new medicines.

Quality indicators are increasingly used as a tool to achieve safe and quality clinical care, cost‐effective therapy, for professional learning, remuneration, accreditation and financial incentives. A substantial number focus on drug therapy but few address the introduction of new medicines even though this is a burning issue. The objective was to describe the issues and challenges in designing and implementing a transparent indicator framework and evaluation protocol for the introduction of new medicines and to provide guidance on how to apply quality indicators in the managed entry of new medicines. Quality indicators need to be developed early to assess whether new medicines are introduced appropriately. A number of key factors need to be addressed when developing, applying and evaluating indicators including dimensions of quality, suggested testing protocols, potential data sources, key implementation factors such as intended and unintended consequences, budget impact and cost‐effectiveness, assuring the involvement of the medical professions, patients and the public, and reliable and easy‐to‐use computerized tools for data collection and management. Transparent approaches include the need for any quality indicators developed to handle conflict of interests to enhance their validity and acceptance. The suggested framework and indicator testing protocol may be useful in assessing the applicability of indicators for new medicines and may be adapted to healthcare settings worldwide. The suggestions build on existing literature to create a field testing methodology that can be used to produce country‐specific quality indicators for new medicines as well as a cross international approach to facilitate access to new medicines.

Improving the managed introduction of new medicines: sharing experiences to aid authorities across Europe

The 3-day course on the managed introduction of new drugs was organised by the Piperska group together with the Agency for Health Technology Assessment and Tariff System (AOTMiT) and WHO Europe to share experiences and case histories among health authority and health insurance company personnel, academics and those from commercial organisations from across Europe on potential ways to optimise the managed entry of new medicines. This starts pre-launch with horizon scanning and budgeting, then peri-launch including critical drug evaluation, and finally post launch including monitoring prescribing of new medicines against agreed guidance and indicators. There were also discussions on issues regarding managed entry schemes and procurement strategies including biosimilars.

How can pricing and reimbursement policies improve affordable access to medicines? Lessons learned from European countries

This article discusses pharmaceutical pricing and reimbursement policies in European countries with regard to their ability to ensure affordable access to medicines. A frequently applied pricing policy is external price referencing. While it provides some benchmark for policy-makers and has been shown to be able to generate savings, it may also contribute to delay in product launch in countries where medicine prices are low. Value-based pricing has been proposed as a policy that promotes access while rewarding useful innovation; however, implementing it has proven quite challenging. For high-priced medicines, managed-entry agreements are increasingly used. These agreements allow policy-makers to manage uncertainty and obtain lower prices. They can also facilitate earlier market access in case of limited evidence about added therapeutic value of the medicine. However, these agreements raise transparency concerns due to the confidentiality clause. Tendering as used in the hospital and offpatent outpatient sectors has been proven to reduce medicine prices but it requires a robust framework and appropriate design with clear strategic goals in order to prevent shortages. These pricing and reimbursement policies are supplemented by the widespread use of Health Technology Assessment to inform decision-making, and by strategies to improve the uptake of generics, and also biosimilars. While European countries have been implementing a set of policy options, there is a lack of thorough impact assessments of several pricing and reimbursement policies on affordable access. Increased cooperation between authorities, experience sharing and improving transparency on price information, including the disclosure of confidential discounts, are opportunities to address current challenges.

Pharmaceutical policies in a crisis? Challenges and solutions identified at the PPRI Conference

In October 2015, the third international Pharmaceutical Pricing and Reimbursement Information (PPRI) Conference was held in Vienna to foster discussion on challenges in pricing and reimbursement policies for medicines. The research presented highlighted that commonly used pharmaceutical pricing and reimbursement policies are not sufficiently effective to address current challenges. Conference participants called for fundamental reforms to ensure access to medicines, particularly to new and potentially more effective and/or safe medicines, while safeguarding the financial sustainability of health systems and working towards universal health coverage.

Policy options to deal with high-cost medicines – survey with European policy-makers.

Background The affordability and financing of new, frequently high-cost, medicines pose challenges to governments world-wide. In Europe, the continual introduction of new premium-priced medicines is of special concern and requires adapted policy options. The aim of the study was to survey whether and which pricing and reimbursement policy options European countries have implemented for new premium-priced medicines.