A1 Differences in equitable access to medicines between European countries
Availability
New medicines are often launched first either in the United States or in Europe. Between 2010 and 2014 for instance, 93 new chemical or biological entities were launched in the US and 83 in Europe, while less than 30 were launched in Japan or other parts oft he world [1].
The actual availability of medicines on the market (i.e. being marketed), however, varies between European countries [2-4]. In the European Union (EU), new medicines have to be granted a marketing authorization by the European Medicines Agency EMA, or by national agencies in rare cases. In principle, companies can launch their product in any EU Member States as soon as it is authorized. However, also in the light of the high prices of (new) medicines, pharmaceutical manufacturers have an interest to have their medicines, at least partially funded, by public payers, and will thus apply for a price of their product and public funding, in line with national regulation. According to European legislation (EU Transparency Directive [5]), pricing and reimbursement procedures should be concluded within 180 days.
These processes, together with manufacturers’ launch strategies, have an impact on the availability of new pharmaceuticals in EU Member States. The European pharmaceutical industry association EFPIA produced the W.A.I.T (Patients Waiting to Access Innovative Therapies) reports. The latest available report showed that the discrepancies ranged from 116 to 515 days between the marketing authorization and the pricing /reimbursement decision for a sample of 66 out-patient medicines, centrally authorized by EMA during 2008-2010, in 20 European countries [6]. Delays in the pricing and reimbursement procedures were reported to be the major cause for these differences [5]. However, marketing authorization holders were also accountable for delays in regulatory processes because their dossiers were not complete or did not contain the required information [2], so there is no comprehensive picture on the availability and on the causes of possible delays in pricing and reimbursement decisions.
Limited availability of medicines on the market also results from companies’ decision to bring a product on the market at a later stage, or to not market at all. A major reason for such strategic launch sequence of marketing authorization holders is the wide-spread use of external price referencing that will be discussed in the main body of the article. Furthermore, companies may decide not to market their products in less-resourced countries because the country cannot afford them at the price the marketing authorization holder asks for, or because the market is not attractive due to its small size [3, 7]. Availability problems have been observed for new on-patent medicines as well as for generics [8, 9].
In addition, limited availability can be attributable to shortages of medicines that were initially marketed but cannot be supplied. Shortages, again, have different reasons; one cause is parallel trade (for a definition see A3) that is allowed and encouraged within the European Union and that incentivizes traders to make use of the arbitrage between lower-priced and higher-priced countries [3, 10-12]. However, increasingly global manufacturing capacity problems have caused shortages, and price pressures on old generic medicines, and this may have pushed manufacturers out of the market.
Medicine prices
Medicine prices vary considerably across European countries. For new medicines, higher-income countries (e.g., Denmark, Germany, Sweden, Switzerland) tend to have higher prices, whereas lower-income European countries, and those hit by the global financial crisis (e.g. Greece, Spain, Portugal), tend to have lower prices [2, 13-18]. While this seems not to be surprising, this pattern is not always seen for all products (e.g. orphan medicines) [19] and countries. Though being high-income economies, France, Norway and UK tend to show lower prices within the spectrum of EU Member States, for instance [20]. Price variation in European countries remains to be observed even if price data are adjusted per gross domestic product [21, 22]. The scenario for generic medicine prices is different: Nordic countries tend to have relatively lower prices in comparison to other European countries [23, 24].
Policy-makers from several European countries consider the high prices of medicines as a major barrier to access [25-29]. If a patient had to pay for the treatment out of pocket, the total cost of a full course of sofosbuvir alone would be equivalent to one year or more of average earnings for individuals in 12 of 30 countries. This has been mainly analysed for European countries [22].
Utilization
Medicine utilization varies across the European countries [30-35], and also within countries [36]. High or low medicine utilization may, or may not, point to inappropriate use, depending on what had been defined as the ideal level of use for specific medicines. There are multiple causes for differences in medicine utilisation across and within different countries, population groups and therapeutic classes such as the market entry of competitor medicines [37] and changes in clinical guidelines. Cultural diversity (e.g. attitudes and beliefs towards psychotropic medicines) is a major cause for cross-country differences; and pharmaceutical policies can also impact uptake of medicines [38, 39]. Reimbursement restrictions of benzodiazepines in the Netherlands have led to a decrease in their use [40]. The lifting of prescribing restrictions on generic losartan in Austria, while still in place for patented angiotensin receptor blockers, resulted in higher uptake [41]. While Finland and Portugal were successful in increasing generic market shares of major antipsychotic medicines through measures to enhance generic uptake, they had, likely unintended, decreases in its overall use of antipsychotic medicines [42]. While a gradient favouring individuals from higher socioeconomic groups in the consumption of non-prescribed medicines was found in eight Central and Eastern Europe countries, for prescribed medicines this was identified in ‘only’ three of the surveyed countries, indicating a possibly positive impact of pharmaceutical policies to reduce socioeconomic inequality [43].
References
1.EFPIA. The Pharmaceutical Industry in figures. Key data 2015. Brussels: European Federation of Pharmaceutical Industries and Associations, 2016.
2.Bouvy J, Vogler S. Background Paper 8.3 Pricing and Reimbursement Policies: Impacts on Innovation. In: World Health Organization, editor. Priority Medicines for Europe and the World "A Public Health Approach to Innovation" Update on 2004 Background Paper. Geneva 2013.
3.Kanavos P, Vandoros S, Irwin R, Nicod E, Casson M. Differences in costs of and access to pharmaceutical products in the EU. Brussels: European Parliament, 2011.
4.Vogler S, Habl C, Leopold C, Rosian-Schikuta I, de Joncheere K, Lyager Thomsen T. PPRI Report. Vienna: Pharmaceutical Pricing and Reimbursement Information, 2008.
5.European Commission. Council Directive 89/105/EEC of 21 December 1988 relating to the transparency of measures regulating the prices of medicinal products for human use and their inclusion in the scope of national health insurance systems. 1998. Available at: (accessed 4 November 2016).
6.EFPIA. Patients' W.A.I.T. Indicator - Report 2011
Accessible from: (accessed 23 June 2016). 2011.
7.Heads of Medicines Agencies. Report of Task Force of HMA. Availability of Human Medicinal Products. Madeira: 2007.
8.Leopold C, Rovira J, Habl C. Generics in small markets or for low volume medicines European Union. Vienna: EMINet, 2010.
9.Carone G, Schwierz C, Xavier A. Cost-containment policies in public pharmaceutical spending in the EU. Brussels: European Commission, Directorate-General for Economics and Financial Afairs, 2012.
10.De Weerdt E, Simoens S, Hombroeckx L, Casteels M, Huys I. Causes of drug shortages in the legal pharmaceutical framework. Regulatory Toxicology and Pharmacology. 2015;71(2):251–8.
11.Pauwels K, Huys I, Casteels M, Simoens S. Drug shortages in European countries: a trade-off between market attractiveness and cost containment? BMC Health Services Research. 2014;14(1):1-9.
12.Gray A, Manasse Jr HR. Shortages of medicines: a complex global challenge. Bulletin of the World Health Organization. 2012;90(3):158-.
13.Vogler S, Kilpatrick K, Babar Z-U-D. Analysis of Medicine Prices in New Zealand and 16 European Countries. Value in Health. 2015;18(4):484–92
14.Vogler S, Vitry A, Babar Z-U-D. Cancer drugs in 16 European countries, Australia, and New Zealand: a cross-country price comparison study. The Lancet Oncology. 2016;17(1):39-47.
15.Kanavos PG, Vandoros S. Determinants of branded prescription medicine prices in OECD countries. Health Economics Policy and Law. 2011;6(3):337.
16.Kanavos P, Ferrario A, Vandoros S, Anderson GF. Higher US Branded Drug Prices And Spending Compared To Other Countries May Stem Partly From Quick Uptake Of New Drugs. Health Affairs. 2013;32(4):753-61.
17.Danzon PM, Furukawa MF. International prices and availability of pharmaceuticals in 2005. Health Affairs. 2008;27(1):221-33.
18.Leopold C, Mantel-Teeuwisse AK, Vogler S, de Joncheere K, Laing RO, Leufkens HGM. Is Europe still heading to a common price level for on-patent medicines? An exploratory study among 15 Western European countries. Health Policy. 2013;112:209-16.
19.Michel M, Toumi M. Access to orphan drugs in Europe: current and future issues. 2012.
20.Brekke KR, Holmås TH, Straume OR. Are Pharmaceuticals Still Inexpensive in Norway? A Comparison of Prescription Drug Prices in Ten European Countries. SNF Report No. 08/10. 2010.
21.Europe Economics. External Price Referencing. London: 2013.
22.Iyengar S, Tay-Teo K, Vogler S, Beyer P, Wiktor S, de Joncheere K, et al. Prices, Costs, and Affordability of New Medicines for Hepatitis C in 30 Countries: An Economic Analysis. PLoS Med. 2016;13(5):e1002032.
23.Simoens S. International comparison of generic medicine prices. Current Medical Research and Opinion. 2007;23(11):2647-54.
24.Vogler S. How large are the differences between originator and generic prices? Analysis of five molecules in 16 European countries. Farmeconomia Health economics and therapeutic pathways. 2012;13 (Suppl 3):29-41.
25.Zimmermann N, Vogler S, Bak Pedersen H. Policy options to deal with high-cost medicines - survey with European policy-makers. Journal of Pharmaceutical Policy and Practice. 2015;8(Suppl 1):P8.
26.WHO Regional Office for Europe. Access to new medicines in Europe: technical review of policy initiatives and opportunities for collaboration and research. Copenhagen: 2015.
27.Ministry of Health WaS. Summary of Medicines Plan. The Hague: 2016. Accessible at: (accessed 14 May 2016).
28.Council of the European Union. Council conclusions on the "Reflection process on modern, responsive and sustainable health systems". Employment, Social Policy, Health and Consumers Affairs. Council meeting. Brussels, 10 December 2013. 2013.
29.European Commission. Council conclusions on innovation for the benefit of patients (2014/C 438/06). Brussels: 6 December 2014.
30.Nolte E, Newbould J, Conklin A. International variation in the usage of medicines - A review of literature. 2010.
31.Nolte E, Corbett J. International variation in drug usage - An exploratory analysis of the “causes” of variation. 2014.
32.Ferech M, Coenen S, Malhotra-Kumar S, Dvorakova K, Hendrickx E, Suetens C, et al. European Surveillance of Antimicrobial Consumption (ESAC): outpatient antibiotic use in Europe. Journal of Antimicrobial Chemotherapy. 2006;58(2):401-7.
33.Hoebert J, Laing R, Stephens P. Pharmaceutical consumption. The world medicines situation 2011. 2011.
34.Jönsson B, Persson U, Wilking N. Innovative Treatments for cancer in Europe - Value, cost, and access. Lund: IHE-Report, 2016.
35.Jönsson B, Hofmarcher T, Lindgren P, Wilking N. Comparator report on patient access to cancer medicines in Europe revisited. IHE report. 2016;4.
36.White R, Mallinson M. Variability In Local Uptake And Patient Access To Medicines-Implementation Of Scottish Medicines Consortium Guidelines. Value in Health. 2013;16(3):A258.
37.Godman B, Persson M, Miranda J, Skiöld P, Wettermark B, Barbui C, et al. Changes in the Utilization of Venlafaxine after the Introduction of Generics in Sweden. Applied health economics and health policy. 2013;11(4):383-93.
38.Hoebert JM. Cross-country variation in medicines use; a pharmaceutical system perspective 2013.
39.Godman B, Shrank W, Andersen M, Berg C, Bishop I, Burkhardt T, et al. Comparing policies to enhance prescribing efficiency in Europe through increasing generic utilization: changes seen and global implications. Expert Reviews. 2010;10(6):707-22.
40.Hoebert JM, Souverein PC, Mantel-Teeuwisse AK, Leufkens HG, van Dijk L. Reimbursement restriction and moderate decrease in benzodiazepine use in general practice. The Annals of Family Medicine. 2012;10(1):42-9.
41.Bucsics A, Godman B, Burkhardt T, Schmitzer M, Malmström RE. Influence of lifting prescribing restrictions for losartan on subsequent sartan utilization patterns in Austria: implications for other countries. Expert Review of Pharmacoeconomics & Outcomes Research. 2012;12(6):809-19.
42.Leopold C, Zhang F, Mantel-Teeuwisse AK, Vogler S, Valkova S, Ross-Degnan D, et al. Impact of pharmaceutical policy interventions on utilization of antipsychotic medicines in Finland and Portugal in times of economic recession: interrupted time series analyses. International Journal for Equity in Health. 2014;13(1):53.
43.Vogler S, Österle A, Mayer S. Inequalities in medicine use in Central Eastern Europe: an empirical investigation of socioeconomic determinants in eight countries. International Journal for Equity in Health. 2015;14(1):124.