The Early Awareness and Alert System in Sweden: History and Current Status.

Introduction: Over the past decades, early awareness and alert (EAA) activities and systems have gained importance and become a key early health technology assessment (HTA) tool. While a pioneer in HTA, Sweden had no national level EAA activities until 2010. We describe the evolution and current status of the Swedish EAA System. Methods: This was a historical analysis based on the knowledge and experience of the authors supplemented by a targeted review of published and gray literature as well as documents relating to EAA activities in Sweden. Key milestones and a description of the current state of the Swedish EAA System is presented. Results: Initiatives to establish a system for the identification and assessment of emerging health technologies in Sweden date back to the 1980s. In the 1990s, the Swedish Agency for HTA and Assessment of Social Services (SBU) supported the development of EuroScan as one of its founder members. In the mid-2000s, an independent regional initiative, driven by the Stockholm County Drug and Therapeutics Committee, resulted in the establishment of a regional horizon scanning function. By 2009, this work had expanded to a collaboration between the four biggest counties in Sweden. The following year it was further expanded to the national level and since then the Swedish EAA System has been carrying out identification, filtration and prioritization of new medicines, early assessment of the prioritized medicines, and dissemination of information. In 2015, the EAA System was incorporated into the Swedish national process for managed introduction and follow-up of new medicines. Outputs from the EAA System are now used to select new medicines for inclusion in this process. Conclusions: The Swedish EAA System started as a regional initiative and rapidly grew to become a national level activity. An important feature of the system today is its complete integration into the national process for managed introduction and follow-up of new medicines. The system will continue to evolve as a response both to the changing landscape of health innovations and to new policy initiatives at the regional, national and international level.

High adherence to the 'Wise List' treatment recommendations in Stockholm: a 15-year retrospective review of a multifaceted approach promoting rational use of medicines.

OBJECTIVES: To present the 'Wise List' (a formulary of essential medicines for primary and specialised care in Stockholm Healthcare Region) and assess adherence to the recommendations over a 15-year period. DESIGN: Retrospective analysis of all prescription data in the Stockholm Healthcare Region between 2000 and 2015 in relation to the Wise List recommendations during the same time period. SETTING: All outpatient care in the Stockholm Healthcare Region. PARTICIPANTS: All prescribers in the Stockholm Healthcare Region. MAIN OUTCOME MEASURES: The number of core and complementary substances included in the Wise List, the adherence to recommendations by Anatomic Therapeutic Chemical (ATC) 1st level using defined daily doses (DDDs) adjusted to the DDD for 2015, adherence to recommendations over time measured by dispensed prescriptions yearly between 2002 and 2015. RESULTS: The number of recommended core substances was stable (175-212). Overall adherence to the recommendations for core medicines for all prescribers increased from 75% to 84% (2000 to 2015). The adherence to recommendations in primary care for core medicines increased from 80% to 90% (2005 to 2015) with decreasing range in practice variation (32% to 13%). Hospital prescriber adherence to core medicine recommendations was stable but increased for the combination core and complementary medicines from 77% to 88% (2007 to 2015). Adherence varied between the 4 therapeutic areas studied. CONCLUSIONS: High and increasing adherence to the Wise List recommendations was seen for all prescriber categories. The transparent process for developing recommendations involving respected experts and clinicians using strict criteria for handling potential conflicts of interests, feedback to prescribers, continuous medical education and financial incentives are possible contributing factors. High-quality evidence-based recommendations to prescribers, such as the Wise List, disseminated through a multifaceted approach, will become increasingly important and should be developed further to include recommendations and introduction protocols for new expensive medicines.

Quality and efficiency of statin prescribing across countries with a special focus on South Africa: findings and future implications.

INTRODUCTION: Statins are recommended first-line treatment for hyperlipidemia, with published studies suggesting limited differences between them. However, there are reports of under-dosing. South Africa has introduced measures to enhance generic utilization. Part one documents prescribed doses of statins in 2011. Part two determines the extent of generics versus originator and single-sourced statins in 2011 and their costs. RESULTS: Underdosing of simvastatin in 2011 with average prescribed dose of 23.7 mg; however, not for atorvastatin (20.91 mg) or rosuvastatin (15.02 mg). High utilization of generics versus originators at 93-99% for atorvastatin and simvastatin, with limited utilization of single-sourced statins (22% of total statins - defined daily dose basis), mirroring Netherlands, Sweden and UK. Generics priced 33-51% below originator prices. DISCUSSION: Opportunity to increase simvastatin dosing through education, prescribing targets and incentives. Opportunity to lower generic prices with generic simvastatin 96-98% below single-sourced prices in some European countries.

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.

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.

Impact of delisting ARBs, apart from losartan, on ARB utilisation patterns in Denmark: implications for other countries.

INTRODUCTION: Renin-angiotensin inhibitor drugs have been a target for health authority initiatives across Europe with the potential for substantial savings once generic angiotensin-converting enzyme inhibitors (ACEIs) became available without compromising care. Recently, losartan was the first angiotensin receptor blocker (ARB) to lose its patent. In Denmark, the authorities removed all other ARBs from the reimbursement list, apart from losartan, as they were all seen as essentially similar for the management of hypertension or congestive heart failure at appropriate doses, but more expensive. Similarly, all other ARB fixed-dose combinations (FDCs), apart from losartan, were removed from the reimbursement list. OBJECTIVE: The aims of the study were to (i) assess the impact of these reimbursement changes on the subsequent utilisation of losartan and other ARBs alone or as FDCs; (ii) assess changes in the prices of losartan and other ARBs post-generic losartan to calculate potential savings; and (iii) compare the impact of the policies in Denmark with other European countries to provide guidance. METHODOLOGY: This was a retrospective segmented regression analysis of an interrupted time-series design comparing utilisation patterns before and after the changes in ARB reimbursement status. Utilisation was measured in defined daily doses (DDDs). Changes in total expenditure and expenditure/DDD were also assessed over time. RESULTS: Losartan utilisation grew from 31 to 33 % of total single ARB utilisation before generic losartan, to 93 % by October 2011. There was a corresponding decrease in the utilisation of all other ARBs. Both changes were significant (p < 0.001). Total expenditure on single ARBs in 2011 was 77 % below 2009 levels despite a 16 % increase in utilisation. Estimated savings were 290.5 million Danish Kroner (DKK). A similar trend was seen for losartan FDCs, which was also significant (p < 0.001). DISCUSSION: Losartan utilisation grew appreciable following the changes. The change was much greater than seen in countries that had eased prescribing restrictions for losartan but not the other ARBs. Active therapeutic switching programmes plus education and financial incentives also significantly enhanced losartan utilisation following generics in two countries and regions; however, the increase in losartan utilisation was less than that seen in Denmark.

Influence of lifting prescribing restrictions for losartan on subsequent sartan utilization patterns in Austria: implications for other countries.

INTRODUCTION: Prescribing restrictions for angiotensin receptor blockers (ARBs) limited their utilization in Austria. Recently, generic losartan became available with its prescribing restrictions lifted while still in place for patented ARBs. OBJECTIVES: The main aim of this study is to assess the impact of the lifting of the prescribing restriction on utilization of losartan in ambulatory care versus other single ARBs, expenditure per defined daily dose (DDD) of losartan as well as total ARB expenditure and utilization of ARB combinations. Finally, to suggest potential measures that could be introduced to further enhance ARB-prescribing efficiency. METHODOLOGY: A quasi-experimental study of the utilization of different ARBs alone or in fixed dose combinations using a segmented time series. Utilization measured in DDDs, defined as 'the average maintenance dose of a drug when used in its major indication in adults'. Costs measured as total expenditure for different ARBs as well as their expenditure/DDD. RESULTS: Losartan utilization increased significantly following the withdrawal of prescribing restrictions (p > 0.001). Utilization of single-sourced ARBs also increased , but the growth rate was appreciably reduced once restrictions were lifted for losartan (p > 0.01). As a result, total expenditure of single ARBs increased but at an appreciably lower rate than utilization, helped by total expenditure/DDD for losartan declining by 78% over the study period. There was continuing appreciable utilization of fixed-dose combinations. CONCLUSION: Lifting of prescribing restrictions for losartan significantly enhanced its utilization, increasing ARB-prescribing efficiency, providing direction to other European authorities. Additional reforms are being considered to further switch utilization away from single-sourced ARBs to additionally improve prescribing efficiency as more multiple sourced ARBs become available.

Improving the managed entry of new medicines: sharing experiences across Europe.

The 3-day course on the managed entry of new medicines was run by the Piperska group, which is a pan-European group striving to enhance the health of the public as a whole and the individual patient through exchanging ideas and research around the rational use of drugs. Participants included health authority and health insurance personnel, academics and those from commercial organizations. The principal aim of the conference was to bring together people to discuss ways to improve the managed entry of new drugs.

Imperative to consider multiple initiatives to maximize prescribing efficiency from generic availability: case history from Abu Dhabi.

INTRODUCTION: Pharmaceutical expenditure has risen rapidly in Abu Dhabi, resulting in policies surrounding generics. However, various circumstances will reduce potential savings, including pharmacists still being free to dispense either originator or branded generics and be fully reimbursed. OBJECTIVES: To research the changes in utilization patterns of proton pump inhibitors (PPIs) and lipid-lowering drugs before and after combined reforms on generics; and subsequently, calculate potential savings based on 'best practices' among Western European countries. METHODS: An uncontrolled before-and-after observational study of utilization and expenditure of PPIs, statins and ezetimibe between 2004 and 2010, as well as up to 12 months before the first generic policy, to 1 year after the second generic policy, was carried out. Utilization was converted to defined daily doses (DDDs; 2011 DDDs) and DDDs/1000 inhabitants per day. Expenditure/DDD was calculated for omeprazole and simvastatin. RESULTS: PPI utilization rose by 6.5-fold from 2004 to 2010, principally driven by increased utilization of patent-protected PPIs, although more recently stabilization in esomperazole utilization has occurred. Similar changes were seen for statins. Introduction of best practices would reduce PPI expenditure in 2010 by 32.8 million United Arab Emirates dirham (AED; €6.26 million) and statins by over 27 million AED (€5.15 million). CONCLUSION: Limited demand-side measures led to increased utilization of patent-protected products in Abu Dhabi following the generic reforms. Successful measures will release considerable resources.