Table A1.

Pricing approaches for generics and major demand-side measures principally for the PPIs and statins among the different European countries typically up to 2007 (Von Ferber et al., 1999; Schmacke and Lauterberg, 2002; Wessling and Lundin, 2006; Hyde, 2007; Magrini et al., 2007; Office of Fair Trading, 2007; Peura et al., 2007; Sakshaug et al., 2007; Fattore and Jommi, 2008; Festoy et al., 2008; Godman et al., 2008a,b, 2009b,c, 2010a,b,c; Simoens, 2008a; Teixeira and Vieira, 2008; Wettermark et al., 2008, 2009a,b, 2010a; Eriksson and Lundin, 2009; Adamski et al., 2010; Barry et al., 2010; DoH, 2010; Martikainen et al., 2010; McGinn et al., 2010; Sermet et al., 2010; Stock et al., 2010).

Country	Key supply and demand-side reforms
AT – Austria	Generic pricing (mixed approach)    Initially first generic 48% below originator, with originator mandated to lower its price by 30% for continued    reimbursement; second generic 15% below the first to be reimbursed; third generic 10% lower than the second    (overall 60% below pre-patent loss prices)    Market forces after that with physicians incentivized to prescribe cheapest branded generics Demand-side measures    Education – includes guidance and benchmarking    Economics – includes financial incentives for physicians to enhance efficient prescribing including the cheapest    generic in the class    Enforcement – Prescribing restrictions for both atorvastatin and rosuvastatin (prior approval scheme via the Chief    Medical Officer of the patient's social health insurance fund)
DE – Germany	Generic pricing    Market forces for generics along with reference pricing in the class (PPIs and statins) Demand-side measures (variation among the States)    Educational initiatives – include prescribing guidance, quality circles and web based training programs    Economics – includes budgets, financial incentives linked with prescribing targets and patient co-payments for a    more expensive molecule than the referenced priced product (molecule or class)    Engineering – includes Disease Management programs, price: volume agreements, rebate contracts between    pharmaceutical companies and Sickness Funds and prescribing targets    Enforcement – Atorvastatin delisted from the normal reimbursement list in 2003 following the instigation of    reference pricing for the statins (“Jumbo Class”)
EE – Estonia	Generic pricing    Third generic 43% below originator prices; market forces after that Demand-side measures    Education – prescribing information to physicians    Economics includes co-payment for the PPIs and statins       PPIs – 50% co-payment       Statins – 10–25% co-payment, rosuvastatin 50% co-payment in patients with familial hypercholesterolemia (total       cholesterol > 8 mmol/l) and following a CV event (total cholesterol > 4.5 mmol/l)    Enforcement for the statins – reimbursement only for restricted indications otherwise 100% co-payment
ES – Spain and regions (Catalonia)	Generic pricing    Currently market forces driving down generic prices. This may change to a mixed approach Demand-side measures (some variation among Autonomous Communities including Catalonia)    Education – includes benchmarking, guidance and educational courses    Economics – includes financial incentives for physicians to meet agreed prescribing targets    Engineering – includes prescribing targets    Enforcement – includes mandatory for pharmacists to dispense cheapest molecule if the prescribed product is more    expensive than current reference price, which is usually a generic. This must be generic if the same price as the drug    prescribed. No opportunity for patients to cover any additional costs themselves
FI – Finland	Generic pricing    Mixed approach to the pricing of generics. The price of the first generic has to be 40% lower than the price of the    original product to be reimbursed    Prices of subsequent generics must not be higher than the first generic to be reimbursed with market forces driving    down prices with the introduction of generic substitution with the cheapest product from 2003. Substitution    mandatory unless forbidden by the physician or patient; although there can be higher co-payments for more    expensive products Demand-side measures    Education – clinical guidelines as well as EBM initiatives to enhance the quality of prescribing. However, no    prescribing targets as seen in a number of other European countries    Economics – principally via patient co-payments       2001: PPIs – €8.41/purchase plus 50% co-payment (Basic Refund Category), similarly for statins for most patients.       Patients with familial hypercholesterolemia or coronary artery disease entitled to lower co-payment at €4.20/       purchase and 25% co-payment       2007: PPIs 58% co-payment; similarly for the statins unless familial hypercholesterolemia or coronary artery       disease entitlement where only 28% co-payment (applied to 15% of statin users)    Enforcement – in 2006 atorvastatin and rosuvastatin restricted to second line as appreciably more expensive than    other statins with limited additional benefit (restriction for atorvastatin subsequently abolished in 2009 with the    availability of generic atorvastatin and reference pricing for the molecule)
FR – France	Generic pricing    Prescriptive pricing for generics with the first generic priced 55% below the originator for reimbursement. Prices    further reduced by 7% after 18 months. Demand-side measures    Education – includes campaigns to enhance the prescribing and dispensing of generics through for instance    benchmarking of physician prescribing and campaigns to allay fears regarding generics    Economics       Incentives to physicians, patients and pharmacists to enhance the prescribing and dispensing of generics versus       originators including encouraging physicians to prescribe by INN name       Co-payments – working out on average 20% for PPIs and statins (when factoring in patients with long term illness)    Engineering       Price: volume agreements for existing compounds)       Campaigns from 2009 to enhance the prescribing of generics in a class through prescribing targets linked       with financial incentives (CAPI – Contrats d'amélioration des pratiques individuelles) prescribing targets       (engineering)
GB – England	Generic pricing    Market forces with transparency in pricing of generics coupled with high INN prescribing. This has typically resulted    in low prices for generics Demand-side measures (national and local with some variation among Primary Care Trusts)    Education – includes for instance national and local prescribing guidance (e.g., NICE, British National Formulary and    PCT prescribing guidance), benchmarking and academic detailing    Economics – budget devolution, Practice Based Commissioning and physician financial incentives    Engineering – includes Better Care, Better Value indicators for low cost PPIs and statins as well as prescribing support    programs encouraging active therapeutic substitution. In addition, proactively managing the introduction of new    generics through encouraging the prescribing of patent protected products in a class that will soon lose their patent    ahead of other single sourced products in a class
GB – Scotland	As for England However, budgets not devolved locally (GPs responsible for their drug budgets but not accountable)
HR – (Croatia)	Generic pricing    Mixed approach. The first generic should not be priced higher than 70% of the originator pre-patent price to be    reimbursed (originator price dropping by at least 10%)    Second generic – a maximum of 90% of the price of the first generic for reimbursement; third generic maximum    price of 90% of the second with market forces further lowering prices with patients paying the difference for a more    expensive molecule than the current reference Demand-side measures    Education – National formulary providing prescribing guidance, with only a limited number of treatment guidelines    Engineering includes – price: volume agreements – although applies to new drugs    Economics includes higher co-payments for more expensive products that the reference molecule. It also includes    co-payments for the statins and PPIs       For the statins – in 2003 – 25% co-payment for secondary prevention in patients with ischemic heart disease or       cerebrovascular disease and with patients with diabetes with a TC > 5 mmol/l; 75% for patients for primary       prevention whose 10-year chance of CHD >20% or will be at the age of 60. Reimbursement only if treatment       initiated for patients <70 years       In 2006, similar to 2003 for secondary prevention (25%). Primary prevention includes TC > 7 mmol/l after 3 months       diet (75% co-payment).       In 2008 (outside study period), no co-payment for patients meeting criteria for primary and secondary       prevention – co-payment only if they wish originator atorvastatin       For the PPIs – typically no co-payment in patients where H2 blockers no longer working for esophageal reflux,       alternatively for Zollinger Elisonov syndrome or eradication of Helicobacter pylori; otherwise 100% co-payment    Enforcement – Access to patient history to check criteria for reimbursement, e.g., statins and PPIs
IE – Republic of Ireland	Generic pricing    Overall mixed approach with the recent introduction of a two step price reduction process for patent expired    products – 20% reduction on patent expiry (in 2007) followed by a further 15% reduction after 22 months (in 2011)    (expected to realise €275 mn by 2011) Demand-side measures    Limited demand-side reforms to date to encourage the prescribing of generic drugs first line
IT – Italy	Generic pricing    The first generic 20% below the originator; market forces after that Demand-side measures (Variation among health authorities)    Educational initiatives – guidelines, academic detailing and benchmarking    Economics – financial incentives for GPs, additional patient co-payment for more expensive molecules than the    reference molecule    Engineering – capping ambulatory care budgets    Enforcement – prescribing restrictions for certain indications
LT – Lithuania	Generic pricing    Currently first generic 30% below originator, second and third generics 10% below this; market forces after that Demand-side measures    Education – some guidelines in place to encourage rational use of medicines but not obligatory. In addition auditing of    prescribing habits with possible financial penalties for excessive costs    Economics – includes co-payments for PPIs and statins, as well as possible financial penalties for physicians (above)       PPIs – 50%+ for majority of indications       Statins - Only 20% co-payment. Initially statins only reimbursed for secondary prevention (post event) and for only       6 months. Reimbursement restrictions now lifted for generic statins    Engineering – includes obligatory INN prescribing unless concerns ( compulsory from 2010 unless prior authorization    from Hospital or Polyclinic Therapeutic Committee)    Enforcement (statins only) – reimbursement only post AMI and only for 6 months (reimbursement restrictions now    lifted for generic statins). In addition, the first prescription must be written by a cardiologist otherwise 100%    co-payment
NO – Norway	Generic pricing    Aggressive prescriptive pricing policy for generics with high volume generics 85% below originator prices Demand-side measures    Limited educational initiatives during the study period    Enforcement       PPIs – prescribing of esomeprazole restricted in 2007. Specialists though required to verify the diagnosis and       recommend therapy       Statins – atorvastatin restricted from 2005 (rosuvastatin not reimbursed) with physicians encouraged to actively       substitute patients currently prescribed atorvastatin. Spot checks undertaken amongst physicians if abuse suspected
PO – Poland	Generic pricing    Market forces driving down generic prices. In addition reference pricing in a class and across therapeutic groups (ATC    Levels 3 and 4) Demand-side measures    Education – generally limited educational interventions; although variable among the regions    Economics – includes co-payment for the indication as well as additional co-payment for a more expensive brand than    the reference product (molecule, class, or therapeutic area)       PPIs – 30% (apart from esomeprazole which is not reimbursed)       Statins – 30% (apart from rosuvastatin which is not reimbursed)    Enforcement – Pharmacists are obliged to inform patients about generic products if they have the same active ingredient,    dosage, package and route of administration as the prescribed product but cheaper (as branded generics in Poland)
PT – Portugal	Generic pricing    Mixed approach to the pricing of generics with the first generic priced at least 35% below the originator; this reduces    to 20% if the originator price is below €10/pack. Further price reductions in 2005, 2007, and 2008    2005 and 2007 – 6% price reduction for all reimbursed medicines    After March 2007 also annual price reductions for generics depending on the market share of each active substance    (5, 9, or 12%)    2008 – further 30% price reduction for generic medicines    2010 – further changes to try and reduce prices within homogeneous groups, i.e., same active substance,    pharmaceutical form, strength and route of administration    In addition, ongoing activities by pharmaceutical companies to suspend market authorization for generics as a    counter measure. The official database from Infarmed (July 2010) includes 17 active substances and more than 500    medicines (packages) where marketing authorization has been suspended
	Demand-side measures    Education – includes guidelines (although not mandatory) and campaigns promoting generics. The latter include    patient campaigns via TV, radio, leaflets in hospitals and community pharmacies as well as physicians updated every    quarter by INFARMED of available generics    Economics – includes establishing a Reference Price System (RPS) in 2002 defining a fixed amount paid by the NHS    for homogeneous groups. In May 2010 no co-payment for pensioners (100% reimbursement) whose income is    below the national minimum wage (the so called Special Regime). In June 2010, new legislation reimbursing 100%    only the five cheapest medicines in a homogeneous group    Engineering – Agreements between the Portuguese Pharmaceutical Industry (represented by APIFARMA) and the    Ministry of Health with the objective of limiting the growth in the NHS expenditure on pharmaceuticals    Enforcement – includes since 2002 an obligation for physicians to prescribe by INN for medicines with approved    generics; however they can prohibit substitution where patient concerns. Pharmacists are allowed to substitute    generics where physicians have prescribed by INN name and have not prohibited substitution, and should also inform    patients about generic prices versus originators (however no financial incentives for this)
RS – Serbia	Generic Pricing    Mixed approach with the first generic priced at least a minimum of 80% of average current prices in three reference    countries (Slovenia, Croatia and Italy)    Subsequent generics should be priced similar or lower to gain market share with the lowest price product    establishing the reference price for the molecule    In addition, to help further lower prices originator and generic drugs must now have the same price for    reimbursement with no opportunity for patients to pay an additional co-payment for a more expensive product Demand-side measures    Economics - Patients initially required to pay an additional co-pay for a more expensive product than the current    reference price (same INN name - ATC Level 5) - now changing (above). Prescribing efficiency helped by early    availability of generics – similar to the situation in Poland (above)    Enforcement – Prior authorization schemes in place for selected premium priced drugs based on step therapy    approaches
SE – Sweden	Generic pricing    Market forces driving down prices with compulsory generic substitution Demand-side measures (some variation among the Counties)    Education – includes a range of measures incorporating prescribing guidance and guidelines, routine benchmarking    against colleagues and against recommended drugs, as well as electronic prescribing support systems    Economics – includes devolved budgets and financial incentives    Engineering – includes prescribing targets such as % of statins as generic statins    Enforcement – includes prescribing restrictions for rosuvastatin (since launch) and atorvastatin (post 2007)
SI – Slovenia	Generic pricing    First generic no higher than an average of 82% of prices in Austria, France and Germany; market forces after that Demand-side measures    Education – includes the Health Insurance Institute organizing therapeutic meetings and undertaking audits of    prescribing habits    Economics – includes additional co-payments for more expensive compounds than the reference product    Enforcement – includes prescribing restrictions for certain drugs based on their more limited value versus current standards
TR – Turkey	Generic pricing    The first generic must be priced no higher than 66% of the originator's pre-patent loss price; subsequently subject to    a 11% price reduction Demand-side measures    Education – limited activities to date    Enforcement – some prescribing restrictions but not applying to PPIs or statins