Accepted for publication Woerkom, Piepenbrink et al

Ongoing measures to enhance the efficiency of prescribing of PPIs and statins in the Netherlands; influence and future implications Menno van Woerkom1, JF (Hans) Piepenbrink2, *Brian Godman3,4,5, Joost de Metz1; Stephen Campbell6, Marietta Eimers1; Lars L Gustafsson3 Dutch Institute for Rational Use of Medicines, Churchillaan 11, 3527 GV Utrecht, Netherlands College voor zorgverzekeringen [Health Care Insurance Board], Eekholt 4, 1112 XH Diemen, Netherlands Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-141 86, Stockholm, Sweden; 4Institute for Pharmacological Research ‘Mario Negri’, Via Giuseppe La Masa 19, 20156 Milan, Italy; 5Prescribing Research Group, University of Liverpool Management School, Chatham Street, Liverpool, UK L69 7ZH Email: Brian.Godman@ki.se Telephone + 46 585 810 68 Fax + 46 585 810 70 Primary Care Research Group, University of Manchester, United Kingdom M13 9PL Key words: Pharmaceuticals, reforms, Netherlands, demand measures, indicators, generics, PPIs, statins, drug utilisation studies *Author for correspondence (Accepted for publication in November in the Journal of Comparative Effectiveness Research Please keep CONFIDENTIAL) Abstract Introduction: Multiple reforms have recently been introduced in the Netherlands to improve prescribing efficiency These include preference pricing policies for multiple sourced products, guidelines, quality and efficiency targets, as well as regular pharmacotherapy meetings Objectives: Assess the influence of these multiple measures on prescribing efficiency Methods: Retrospective observational study of all reimbursed prescriptions for the proton pump inhibitors (PPIs) and statins between 2000 and 2010 using the GIP (Health Insurance) database Utilisation measured in defined daily doses Narrative review of reforms Results: Reimbursed expenditure for the PPIs fell by 58% in 2010 vs 2000 despite a fold increase in utilisation, helped by increasing utilisation of generic omeprazole at only 2% of the pre-patent loss price in 2010 Similarly, reimbursed expenditure for the statins fell by 14% in 2010 vs 2000 despite a 3.8 fold increase in utilisation Again, helped by increasing utilisation of generic simvastatin at only 2% of the pre-patent loss originator price Conclusion: Multiple supply- and demand-measures, including the preference pricing policy, appear to have appreciably enhanced PPI and statin prescribing efficiency, providing examples to other countries Introduction Scrutiny over pharmaceutical expenditure, including prescribing patterns and acquisition costs of generics, originators and patent protected products in a class or relates class, has intensified in recent years with the growth in pharmaceutical expenditure generally outstripping that of other components of ambulatory care expenditure [1-10] As a result, pharmaceutical expenditure has typically become the largest or equalling the largest cost component in ambulatory care [1-12] The growth rate will continue unless addressed, driven by well known factors including changing demographics, rising patient expectations and the continued launch of new expensive drugs [8-11] This has resulted in health authorities and health insurance agencies across Europe instigating multiple supply and demand side reforms to maintain the European ideals of comprehensive and equitable healthcare Supply-side reforms for existing drugs include price: volume agreements with payback mechanisms for over budget situations, compulsory price cuts as well as measures to obtain low prices for generics [1-6,8,12] Demand side measures, collated under the Es – Education, engineering, economics and enforcement [13], include [1,3-7,9,10,14-28]: • Educational activities – These range from simple distribution of printed material to more intensive strategies including academic detailing and monitoring of prescribing habits Examples include local, regional and national formularies The ‘Wise Drug’ list in Stockholm County Council, • • • containing approximately 200 drugs covering conditions typically encountered in ambulatory care, provides an example of a regional formulary Prescribing suggestions in the ‘Wise List’ generally include older well-established and well-documented drugs, typically available as generics, rather than newly marketed drugs Other initiatives include educating physicians in medical school to prescribe by INN (International Non-Proprietary Name), backed up by programmes in ambulatory care to enhance the use of generics when available, e.g UK, as well as information and other campaigns to allay patients’ fears about the effectiveness and/ or safety of generics should they occur, e.g France Engineering activities - Refers to organisational or managerial issues to influence change, e.g quality and prescribing targets as well as pro-active drug switching programmes Quality indicators include BP and lipid targets for patients with cardiovascular disease in the UK Efficiency indicators include percentage prescribing targets for generic drugs within a class or related class such as the percentage of generic proton pump inhibitors (PPIs) prescribed versus all PPIs, percentage of generic statins prescribed versus all statins and the percentage of Angiotensin Converting Enzyme Inhibitors (ACEIs) prescribed versus all renin-angiotensin inhibitor drugs Examples also include active drug switching programmes such as switching patients from atorvastatin to generic simvastatin and high cost angiotensin receptor blockers (ARBs) to lower cost ARBs Economic interventions – Refers to financial incentives These include financial incentives for physicians if they achieve agreed prescribing targets in a class, devolution of drug budgets to local GP groups combined with regular monitoring of prescribing behaviour, as well as fines for physicians with prescribing costs above agreed limits Initiatives also include co-payments, especially if patients wish a more expensive product than the current reference priced product, as well as payments to pharmacists to speak with patients to allay any fears regarding generics Enforcement – These include regulations by law such as compulsory INN prescribing, e.g Abu Dhabi and Lithuania, compulsory generic substitution in Sweden, and prescribing restrictions for patented statins in Austria, Finland, Norway, and Sweden, ARBs in Austria, Croatia, Lithuania and Sweden, and esomeprazole in Norway, limiting the prescribing of these drugs to second line after generics In the Netherlands, there have been active programmes during the past years to lower the price of generics as well as enhance their utilisation versus premium priced patented products in a class or related class Reforms to lower the price of generics include [29-31]: • In 1991 introducing the Drugs Reimbursement System whereby drugs belonging to the same group of therapeutically equivalent drugs were placed in groups of comparable drugs, and the mean average price per standard dosage established the maximal reimbursement price (reference pricing system) • From 1991, pharmacists were allowed to keep any discounts they received from generic manufacturers to preferentially dispense their product • From 1996, prices of generics were based on average prices of originators and generics (same active substance, strength and dosage form) in Belgium, France, Germany and the UK In addition, pharmacists were actively encouraged to substitute by being able to retain 33% of the price difference between the current reference price for the molecule and the prescribed product • In 1998, a claw back system was instigated to enhance potential savings for the insurers from the increasing availability of generics; however this was only partially successful • In 2004, a covenant was instigated whereby generics should be priced at least 40% below the originator for reimbursement, with further agreements after this for both generics and originators to prevent that the Dutch authorities from introducing harsher measures, e.g for the statins • Introduction of the preference pricing policy in 2008 whereby only the cheapest generics would be reimbursed, with patients having to cover the costs themselves for a non-preferred drug Tenders were conducted for high volume generics among the various manufacturers to help achieve low prices This resulted in appreciable price reductions of between 76% to 93% for the 10 largest generics by volume, leading to estimated savings of €348mn/ year The scheme was extended in 2009 as more generics became available As a result, pharmaceutical expenditure has stabilised in the Netherlands in recent years Table documents the multiple demand-side measures that have been introduced in the Netherlands during the past decade to enhance the quality and efficiency of prescribing, especially for the PPIs and statins These have again been divided into the 4Es (Education, Engineering, Economics and Enforcement) to enhance comparisons with other countries [13], some of whose reforms have been described above Table – Demand side measures during the past decade with specific reference to the Proton Pump Inhibitors (PPIs) and statins [13, 39,51-58] Measure Education Economics Engineering Enforcement • Description Production and dissemination of guidelines for use in primary healthcare This includes the NHG Guideline on Gastric symptoms (2003) indicating that only a limited number of patients under 60 should be on chronic PPIs • National network of monthly Pharmacotherapy Audit Meeting groups (PTAM-groups) There is a tradition of continuous medical education in the Netherlands with groups typically including 10 GPs and Pharmacists This can include areas of prescribing concern leading to benchmarking, target setting and evaluation There are various levels of activity, with GPs financially rewarded for taking part The level depends on the extent of the activities undertaken • Prescription feedback by individual pharmacists (linked with PTAM meetings and other meetings) • Prescription feedback by the national databank of pharmacists (from 2002 onwards) • Multidisciplinary guideline on Cardiovascular Risk Management (CVRM) (2006) advocating pravastatin and simvastatin first line with atorvastatin and rosuvastatin second line in patients not achieving target lipid levels with either simvastatin or pravastatin - in view of the cost differential • Along with this, targets to enhance the number of CVD and diabetes patients on statins as well as the appropriateness of the dose prescribed • Financial incentives by health insurance for GPs to follow guidelines and take part in PTAM group meetings (above) The level of remuneration differs between Health Insurance groups • Preference pricing policies for generics including economic incentives to pharmacists to negotiate further price reductions These include targets suggested by the Institute for the Rational Use of Medicines based on regional data in the Netherlands, as well as other countries, and health insurers and include: • Quality o PPIs – Number of chronic PPI users up to 60 years of age versus the total number of patients in the population up to 60 years o Statins (Target score 75% o Statins – number of new users of generic statins (pravastatin and simvastatin) versus number of new users of statins Target = >75% • PPIs only reimbursed for long time use (longer than six months) (from 2012) • Other statins instead of simvastatin and pravastatin only reimbursed when authorized by the health insurer (from 2009 onwards) • The GPs must document the rationale in the patient’s notes as well as on the prescription, which can be checked at the pharmacy, to limit possible abuse Consequently, the primary objective of this paper is to assess the influence of these multiple supplyand demand-side measures introduced in the Netherlands during the past decade, including Table 1, on subsequent prescribing efficiency Two high volume classes will be used for the analysis These are the PPIs - Anatomical Therapeutic Chemical (ATC) A02BC, and the HMG CoA reductase inhibitors (statins) - ATC group C10AA [101] They were chosen as they are both high volume prescribing areas in ambulatory care They also contain a mixture of generics, originators and patented products in a class Prescribing efficiency is defined as utilisation growing faster than expenditure, with health authorities and health insurance companies across Europe believing all PPIs and statins are similar in the majority if not all patients [3-5,7,9,10,14,15,21-24,32] Consequently, generic PPIs and statins should be prescribed first line with patented products reserved for unresponsive patients or those patients unable to tolerate generic PPIs or statins These beliefs are endorsed by IDEAL study, which failed to show a significant reduction in coronary vascular events for patients prescribed high dose atorvastatin (80mg/ day) versus low dose simvastatin (20mg/ day) [33], and a recent meta-analysis demonstrating that at comparable doses all statins appear therapeutically equivalent in reducing LDL-C [34] In addition, a recent ecological study showed that outcomes in terms of the subsequent impact of drug treatment on lipid levels were similar whether patients were prescribed formulary drugs (including generic simvastatin) versus non-formulary drugs, which included patented statins [35] Published studies have also shown that patients can be successfully switched between statins without compromising care [23,27], and physicians in the UK extensively use generic simvastatin to achieve agreed target lipid levels in the Quality and Outcomes Framework to maximise their income [5,9,23,36,37] Secondly, if pertinent, suggest additional reforms that could be instigated in the Netherlands to further enhance prescribing efficiency in ambulatory care Lastly, provide insights to other health authorities and health insurance companies as they strive to further increase their prescribing efficiency through additional reforms Methodology This is a retrospective observational study of all ambulatory care patients included in the Genees- en hulpmiddelen Informatie Project (GIP - Health Care Insurance Board) database, which covers almost all patients in the Netherlands This database provides the complete reimbursed prescription medication history of all patients, as well as the pharmacy where the prescription was dispensed, among the Health Insurance population in the Netherlands for the years documented The robustness and validity of the database is assured by regular monitoring and auditing of drugs dispensed The study included all patients dispensed at least one reimbursed prescription for any PPI (ATC – Anatomical Therapeutic Chemical Classification - group A02BC) or statin (C10AA) [101], between 2000 and 2010 These years were chosen because generic omeprazole was reimbursed in March 2002 (lansoprazole in December 2005, pantoprazole in May 2009 and esomeprazole in October 2010) and generic simvastatin in May 2003 (pravastatin in August 2004 and fluvastatin in August 2008) Consequently, provide baseline utilisation and expenditure values Defined daily doses (DDD) as well as DDDs/1000 inhabitants per day (DDD/TID) were used for measuring drug utilization, which is in line with international recommendations [9,10,101,102] DDDs defined as ‘the average maintenance dose of a drug when used in its major indication in adults’ [102] 2011 Defined Daily Doses (DDDs) were used for the study This is in line with International recommendations for conducting drug utilisation and expenditure comparisons between countries [9,10,38,101,102] Reimbursed expenditure was principally used as the perspective is from the health insurer Reimbursed expenditure just includes the costs paid by the health insurer for the various pharmaceuticals, excluding any patient co-payment or pharmacy fee, which varies between countries There has been no allowance for inflation as we wanted to compute the actual influence of the various policies in the Netherlands on reimbursed prices/ DDD over time, as well as compare with other European countries In addition, the tendency of authorities is to cut prices for both patented drugs and generics when pharmaceutical expenditure is rising more rapidly than agreed budgets [1,2,4,5,8,10] Alongside this, a number of European countries establish their initial prices for generics based on originator pre-patent loss prices [8,10] Consequently, the use of reimbursed expenditure, as well as no allowance for inflation, is in line with previous publications [4,5,8-10,23,24,26] Total cost data including pharmacy costs, which is also reimbursed by the health insurers, was also included in the analysis for comparison purposes A narrative review of the ongoing supply and demand side measures was undertaken by one of the co-authors (BBG), principally based on feedback from co-authors in view of the limited number of English language peer-reviewed papers in recent years dealing particularly with demand-side pharmaceutical policy and its influence in the Netherlands For instance, only four relevant papers in Pub Med since 2008 using two key words – Netherlands and pharmaceuticals – at the time of submission No confidence limits were included for expenditure and other calculations since the GIP/ Health Care Insurance Board database comprises nearly all the patients in the Netherlands No sophisticated analyses such as time series analyses, multivariate analysis or regression lines were performed This is recognition of the many different and varied supply and demand side initiatives introduced during the study period, e.g Table 1, alongside variations in the composition and influence of the many PTAM-groups throughout the Netherlands coupled with different financial incentives among insurers for physicians following guidelines and taking part in these meetings, as well as differences in preference pricing policies We accept this reduces the robustness of the findings; however, this reflects reality in the Netherlands Results • PPIs PPI utilisation increased three fold during the course of the study, rising from 28.6DDD/ TID in 2000 to 84.9 in 2010 (Figure 1), with utilisation dominated by omeprazole H blockers were principally used between 2000 and 2004/5 before PPIs dominated the prescribing of drugs to treat acid related disorders of the stomach Figure – Utilisation pattern for the PPIs 2000 to 2010 in DDDs/ TID However, whilst omeprazole dominated PPI utilisation, its % of total PPIs on a DDD basis decreased from 85% of total PPIs in 2000 to 56% in 2006, before climbing to 61% of total PPI utilisation (DDD basis) in 2010 The latest figures [39] suggest that between 89% - 100% of GPs in 2010 in the Netherlands met the efficiency targets for PPI prescribing suggested by the Institute for the Rational Use of Medicines, with a mean score of 95% Concurrent with this, there was growing utilisation of pantoprazole from 9% of total PPI utilisation in 2000 to 20% in 2004 on a DDD basis, before stabilising at 20% to 21% of total PPI utilisation up to 2010 Similarly for esomeprazole, its utilisation rose from 2% in 2001 to 17% of total PPI utilisation on a DDD basis in 2007, before stabilising at 15% of total PPI utilisation in 2010 respectively (Figure 1) The utilisation of generic omeprazole versus the originator steadily increased from 82% in 2003 (first full year of generic availability) to 94% in 2010 There was though lower utilisation of generic versus originator lansoprazole at 77% of total lansoprazole in 2010 Total reimbursed expenditure for the PPIs fell by 58% during the study period, from €16257.4/ 1000 inhabitants/ year in 2000 to €6815.2 in 2010; 62% from 2001 (fully year before multiple sourced omeprazole available) to 2010 This was assisted by falling expenditure/ DDD for each PPI over time, especially generic as well as originator PPIs once multiple sources became available (Figure 2) Figure - Expenditure/ DDD (€) Generic (GN) and Originator (SP) PPIs 2000 to 2010 Overall, reimbursed expenditure/ DDD for generic omeprazole in 2010 was 98% below the pre-patent loss originator price at €0.04/ DDD vs €1.55/ DDD for originator omeprazole in 2001 (Figure 2) This reduction was assisted by the changes in the pricing regulations for generics in 2004, as well as the introduction of the preference price policies in 2008 described earlier Total expenditure on PPIs also decreased during the course of the study period, from €18205.2/ 1000 inhabitants/ year in 2000 to €11564.5 in 2010 However, the percentage reduction was lower at 36% due to an increasing proportion of costs such as pharmacy dispensing fees being included in total rather than reimbursed expenditure As a result, the difference between reimbursed and total expenditure rose from 12% in 2000 to 70% in 2010 • Statins Statin utilisation increased 3.8 fold during the course of the study, rising from 24.7DDD/ TID in 2000 to 88.8 in 2010 (Figure 3) Figure – Utilisation pattern for the statins 2000 to 2010 in DDDs/ TID Simvastatin and atorvastatin were the principal statins used in the Netherlands between 2000 and 2010 However, the utilisation of simvastatin as a percentage of total statin utilisation on a DDD basis decreased from 44% in 2000 to 31% in 2005, before climbing to 49% in 2010 following the CVRM initiatives in 2006 (Table 1) Latest figures [39] suggest that between 71% to 100% of GPs met the prescribing efficiency target for statins suggested by the Institute for the Rational Use of Medicines in 2010 However, only 11% to 100% (mean 57%) and 13% to 100% (mean 61%) met their target scores for the dosing of simvastatin/ pravastatin and atorvastatin/ rosuvastatin respectively Conversely, utilisation of atorvastatin as a % of total statins remained relatively steady at 34% to 37% of total statin DDDs from 2000 to 2008, before dropping to 27% in 2010 The utilisation of atorvastatin and rosuvastatin combined steadily increased from 34% of total statin utilisation (DDD basis) in 2000 to 49% in 2007 and 2008, before falling to 39% of total statin DDDs in 2010 The utilisation of generic simvastatin versus originator simvastatin reached 94% in 2004, the first full year of availability, before climbing to 97% to 98% of total simvastatin on a DDD basis from 2007 onwards Similarly, utilisation of generic pravastatin reached 92% of total pravsatatin DDDs in 2005, the first full year of availability, rising to 95% in 2010 Reimbursed expenditure for the statins increased 139% between 2000 and 2003, rising from €12666 per 1000 inhabitants per year in 2000 to €18904 per 1000 inhabitants per year in 2003 Reimbursed expenditure subsequently remained relatively stable until 2007, before falling to €10870 in 2010 This was a 42% reduction in 2010 versus 2003 levels; and overall a 14% decrease versus expenditure in 2000 This reduction was facilitated by a considerable decrease in expenditure/ DDD of generic statins versus pre-patent loss originator prices, as well as originator prices once multiple products became available (Figure 4) Figure – Reimbursed expenditure (€)/ DDD for generic (GN) and originator (SN) statins from 2000 to 2010 NB Cerivastatin not included as only limited utilisation in 2000 and 2001 before its withdrawal Overall, reimbursed expenditure/ DDD for generic simvastatin in 2010 was 98% below the pre-patent loss originator price at €0.03/ DDD in 2010 versus €1.51/ DDD for originator simvastatin in 2002, i.e just 2% of the originator price pre-patent loss There was a similar reduction (96%) for generic pravastatin at €0.04/ DDD in 2010 versus €1.16/ DDD in 2003 Similar to the PPIs, there was a fall in 2004 following the changes in the regulations for the pricing of generics and a further fall in 2008 following the introduction of the preference pricing policies This against a background of ongoing supply- and demand-sided measures reducing the robustness of any conclusions Total expenditure of statins rose by 3% in 2010 vs 2000 from €14315 in 2000 to €14779 in 2010 This again was driven by an increasing proportion of costs such as pharmacy dispensing fees being added to pharmacy reimbursed costs As a result, the difference between reimbursed and total expenditure again rose from 13% in 2000 (12% for PPIs) to 36% in 2010 (70% for the PPIs) Discussion The multiple supply and demand side measures, including Table 1, introduced in the Netherlands during the past decade appear to have enhanced reimbursed prescribing efficiency for both the PPIs and statins This is shown by a 58% reduction in reimbursed expenditure for PPIs between 2000 and 2010 despite a threefold increase in utilisation during this period In addition, a 14% decrease in reimbursed expenditure for the statins between 2000 and 2010 despite a 3.8 fold increase in utilisation This is similar to the situation in Scotland with its high International Non-proprietary name (INN) prescribing coupled with multiple reforms to enhance the prescribing of generic PPIs and statins once available as well as transparent pricing approaches to lower the cost of generics [23] Overall, reimbursed expenditure for the PPIs in 2010 in Scotland was 56% below 2001 levels despite a threefold increase in utilisation, with reimbursed expenditure for the statins in 2010 only 7% above 2001 levels despite 6.2 fold increase in utilisation since 2001 23] The key reforms to lower the prices of generics appear to be the changes in the pricing regulations for generics in 2004 and the introduction of the preference pricing policy in 2008 However, we cannot state this with certainty given the limitations in the study design However, these findings regarding the influence of the preference pricing policy mirror other publications [29,30] We are also now seeing other European countries learning from the tendering process for generics in the Netherlands, e.g Sweden with their recent introduction of monthly auctions [40] Consequently, we believe this initiative provides an alternative method to other European health authorities and health insurance agencies if needed on ways to further lower their generic prices in addition to measures such as compulsory generic substitution, e.g Sweden [3,8,10,15, 40], as well as increased transparency in the pricing of generics, including discounts offered by generic manufacturers, along with high INN prescribing (compulsory or voluntary), e.g Lithuania and UK [5,6,8,10,16,23] We believe the growth in omeprazole utilisation compared with other PPIs in recent years (Figure 1) will continue, especially with greater scrutiny over GP prescribing habits through regular PTAM-group meetings and prescribing targets established by the health insurers and groups such as the Institute for the Rational Use of Medicines (Table 1) However this remains to be proven In any event, PPI prescribing efficiency will be further enhanced with esomeprazole now losing its patent The rapid fall in reimbursed expenditure/ DDD for generic omeprazole in recent years adds (Figure 4) adds weight to this suggestion However, again this will need to be demonstrated Care is not compromised with increasing utilisation of generic omeprazole, with health authorities across Europe typically perceiving all PPIs as essentially similar [3-5,7-10,14,15,22,23,32] The various measures to enhance the use of generics versus originators, once multiple sourced products become available, also appear to be working with 77% of total lansoprazole DDDs as generics in 2010 and 94% for omeprazole This mirrors the findings in the UK with its high voluntary INN prescribing leading to 98% of all omeprazole and simvastatin dispensed as generics [23], as well as other European countries [3-6,8, 22-24] As stated, it has been difficult in practice to fully disassociate the various demand side measures from each other (Table 1), especially as the intensity of some measures vary over time and with each GP group Consequently, we have been unable to perform any sophisticated analyses such as an interrupted time series analysis or regression analyses, which is a recognised weakness of the paper Having said this, we believe the results demonstrate the influence of the multiple initiatives with improving PPI prescribing efficiency in the Netherlands as seen by major differences in the rate of change of utilisation versus expenditure during the course of the study Consequently, demonstrating again that multiple measures are typically needed to enhance prescribing efficiency [4,5,68,15,22,23,26,41,42] Potential future steps if needed to moderate overall utilisation of PPIs could involve specific DDD/ TID targets for the PPIs among the physicians in their PTAM groups, which have already been introduced among Primary Care groups in Stockholm, Sweden [15] However, this may not be necessary if PPIs continue not to be reimbursed for short term use, and so fewer patients becoming chronic users In addition, from January 2012 should patients persist with antacids for at least six months for acid related stomach disorders, antacids will continue to be reimbursed apart from the first prescription Both these initiatives should reduce the extent of problems that may develop with chronic PPI use [43-48] However, this again remains to be seen The multiple initiatives have appreciably enhanced prescribing efficiency for the statins in the Netherlands This includes greater encouragement of the prescribing of simvastatin and pravastatin in recent years following further demand side measures (Table 1, Figure 3) In addition, high utilisation of generic versus originator statins at 95% to 98% for pravastatin and simvastatin respectively on a DDD basis in 2010 mirroring the situation in Scvotland 23] Prescribing efficiency should further improve with the increasing use of generic pravastatin and simvastatin (Figure 3) as all statins are seen as essentially similar in all or nearly all patients [3-5,7-10,14-17,21-24,32] In addition, in 2012 atorvastatin will lose its patent and be entered into the preference pricing policy scheme However, this remains to be seen although such initiatives are estimated to save at least €100mn/ year (MVK – Personal Communication) As a result, current initiatives should be continued It has been difficult in practice to fully disassociate the multiple and variable demand side measures from each other (Table 1) Consequently, again we were unable to perform more sophisticated analyses such as an interrupted time series analysis so any findings need to be treated with a degree of caution The initiatives to encourage the utilisation of higher strength statins should be welcomed following the Heart Protection and other studies, which recommend 40mg simvastatin, echoing the SIGN guidelines in Scotland [23,49-52,103] However, the DDD/ TID for statins in Scotland was appreciably higher than the Netherlands at 143 in 2010 [23] This may reflect a more rapid move to higher strength simvastatin and atorvastatin in the UK as a result of considerable financial incentives for physicians achieving agreed lipid level targets in patients with CHD, hypertension and diabetes, coupled with recommendations such as the SIGN guidance [5,23,36,37] However, this is difficult substantiate without further research Consequently, we believe there is still room for improvement for GPs in the Netherlands when prescribing simvastatin This includes potentially identifying additional patients for active management as well as potentially increasing the prescribed doses of statins if needed Pharmacists could possibly help with this, building on recent initiatives [53] Alternatively, enhance physician remuneration levels to identify and treat patients to agreed target lipid levels, mirroring the situation in the UK [5,23,36,37] This is a possible consideration for the future The measures to lower reimbursed prices of generics in recent years, including the preference policies and auctions, appear to be working well for high volume generics such as omeprazole and simvastatin following their introduction [Figures and 4] As a result, reimbursed expenditure/ DDD for generic omeprazole in 2010 was appreciably lower in the Netherlands than generally seen across Europe in 2007 and in the UK in 2010 (Table 2) Total expenditure/ DDD for omeprazole was €0.57 in 2007 dropping to €0.19 in 2010 There was a similar reduction for simvastatin, dropping from €0.53 in 2007 to €0.14 in 2010 Table – Comparative reimbursed expenditure/ DDD (€) for generic omeprazole and simvastatin among European countries in 2007 unless stated [5,6,8,16,23,59-61] NB: Austria and Germany = total expenditure Consequently overall, we believe there is limited opportunity to introduce additional measures to further lower the reimbursed prices for generic omeprazole and generic simvastatin The only way to reduce total expenditure would be to reduce payments to pharmacists, similar to the UK [40] In conclusion, the multiple supply- and demand-measures and initiatives introduced in the Netherlands in recent years have enhanced prescribing efficiency for both the PPIs and statins These include measures to obtain low reimbursed expenditure/ DDD for both generic omeprazole and simvastatin through recent preference pricing and other policies The various initiatives also appear to increas the dose of statins prescribed; although there are opportunities for further improvement As a result of the prescribing efficiencies that have been achieved for the PPIs and statins, we believe there are only limited additional measures that could potentially be introduced in the Netherlands to to further improve prescribing efficiency in ambulatory care The results have also confirmed that multiple measures are typically needed to appreciably improve prescribing efficiency Finally, we hope some of the measures described in the paper provide examples to other European countries as they strive to further enhance their prescribing efficiency with ever greater pressure on resources • • • Scrutiny over pharmaceutical expenditure is increasing across Europe leading to the instigation of multiple supply- and demand-side measures to maintain the European ideals of equitable and comprehensive healthcare Multiple supply side measures introduced in the Netherlands in recent years include measures to lower the price of generics, e.g covenants signed in 2004 whereby generics should be priced at least 40% below the originator to be reimbursed followed later by preference pricing policies Multiple demand side measures introduced in the Netherlands in recent years include a national network of monthly Pharmacotherapy Audit Meeting groups (PTAM-groups) with GPs incentivised to take part, prescription feedback by individual pharmacists (linked with PTAM meetings and other meetings), prescription feedback by the national databank of pharmacists (from 2002 onwards), multidisciplinary guideline on Cardiovascular Risk Management (CVRM) advocating pravastatin and simvastatin first line with documentation in patients’ notes if not followed, financial incentives for GPs as well as quality and efficiency targets 10 • • • • Reimbursed expenditure for the PPIs fell by 58% in 2010 vs 2000 despite a fold increase in utilisation (DDD based), aided by increasing use of generic omeprazole vs other PPIs at 2% of pre-patent loss originator prices (expenditure / DDD) by the end of the study period Reimbursed expenditure for the statins fell by 14% in 2010 vs 2000 despite a 3.8 fold increase in utilisation, aided by increasing use of generic simvastatin at 2% of pre-patent loss prices by the end of the study period There were similar findings in Scotland with their intensive multiple supply- and demand-side measures to enhance prescribing efficiency for the PPIs and statins In both these drug classes, all drugs are seen as essentially similar in all or nearly all patients As a result, multiple and intensive supply- and demand-side measures enhance prescribing efficiency in ambulatory care, with both needed to achieve the results seen in the Netherlands and Scotland Financial & competing interests disclosure J.F (Hans) Piepenbrink works for the Health Care Insurance Board (CVZ: College voor zorgverzekeringen) in the Netherlands, and is responsible for the national information system (database) on drug use (GIP: Genees- en hulpmiddelen Informatie Project) The Institute for the Rational Use of Medicines is funded 50% by the Ministry of Health in the Netherlands; the remainder through assignments and projects for healthcare organisations including pharmacy organisations The authors acknowledge the help of Fredrik Granath from the Karolinska Institutet, Stockholm, Sweden, for his helpful advice regarding statistical analyses The analysis and production of this paper was assisted by a grant from the Karolinska Institute The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those discussed No writing assistance was utilized in the production of this manuscript References Sermet C, Andrieu V, Godman B, Van Ganse E, Haycox A, Reynier JP Ongoing pharmaceutical reforms in France; implications for key stakeholder groups Applied Health Economics and Health Policy 2010;8:7-24 Godman B, Bucsics A, Burkhardt T, Haycox A, Seyfried H, Wieninger P Insight into recent reforms and initiatives in Austria; implications for key stakeholders Expert Rev Pharmacoeconomcis Outcomes Research 2008; 8:357-371 Wettermark B, Godman B, Andersson K, Gustafsson LL, Haycox A, Bertele’ V Recent national and regional drug reforms in Sweden – implications for pharmaceutical companies in Europe Pharmacoeconomics 2008; 26: 537-50 Coma A, Zara C, Godman B, Augusti A, Diogene E et al Policies to enhance the efficiency of prescribing in the Spanish Catalan Region: impact and future direction Exp Review of Pharmacoeconomics and Outcomes Research 2009; 9: 569-81 McGinn D, Godman B, Lonsdale J, Way R, Wettermark B, Haycox A Initiatives to enhance the quality and efficiency of statin and PPI prescribing in the UK; impact and implications Expert Rev Pharmacoeconomics and Outcomes Res 2010; 10: 73-85 Garuoliene K, Godman B, Gulbinovič J, Wettermark B, Haycox A European countries with small populations can obtain low prices for drugs: Lithuania as a case history Expert Rev Pharmacoeconomics Outcomes Res 2011; 11: 341-7 11 Abuelkhair M, Abdu S, Godman B et al Imperative to consider multiple initiatives to maximise prescribing efficiency from generic availability: case history from Abu Dhabi Expert Review Pharmacoeconomics and Outcomes Research 2012; 12: 115-124 Godman B, Shrank W, Wettermark B et al Use of generics – a critical cost containment measure for all healthcare professionals in Europe? Pharmaceuticals 2010; 3:2470-94 doi 10.3390/ph/3082470 ISSN 1424-8247 Godman B, Shrank W, Andersen M et al Comparing policies to enhance prescribing efficiency in Europe through increasing generic utilisation: changes seen and global implications Expert Rev Pharmacoeconomics Outcomes Res 2010; 10: 707–22 10 Godman B, Shrank W, Andersen M et al Policies to enhance prescribing efficiency in Europe: findings and future implications Frontiers Pharmacol 2011; (141): 1-16 doi: 10.3389/fphar.2010.00141 11 Garattini S, Bertele V, Godman B, Haycox A, Wettermark B, Gustafsson LL Enhancing the rational use of new medicines across European healthcare systems – A Position Paper Eur Jn Clinical Pharmacology 2008; 64:1137–8 12 Adamski J, Godman B, Ofierska-Sujkowska G, Osinska B, Herholz H et al Review of risk sharing schemes for pharmaceuticals: considerations, critical evaluation and recommendations for European payers BMC Health Services Research 2010, 10:153 doi:10.1186/1472-6963-10-153 13 Wettermark B, Godman B, Jacobsson B, Haaijer-Ruskamp F Soft regulations in pharmaceutical policymaking - an overview of current approaches and their consequences Appl Health Econ Health Policy 2009; 7: 137-47 14 Godman B, Malmstrom RE, Bennie M et al Prescribing restrictions - a necessary strategy among some European countries to enhance future prescribing efficiency? Reviews in Health Care 2012; 3: 5-16 15 Godman B, Wettermark B, Hoffman M, Andersson K, Haycox A, Gustafsson LL Multifaceted national and regional drug reforms and initiatives in ambulatory care in Sweden; global relevance Expert Rev Pharmacoeconomcis Outcomes Research 2009; 9:65-83 16 Godman B, Wettermark B, Bishop I et al European payer initiatives to reduce prescribing costs through use of generics GABI 2012; 1:22-27 17 Petterson B, Hoffmann M, Wandell P, Levin L-A Utilisation and costs of lipid modifying therapies following health technology assessment for the new reimbursement scheme in Sweden Health Policy 18 Wettermark B, Godman B, Neovius M et al Initial effects of a reimbursement restriction to improve the cost-effectiveness of antihypertensive treatment Health Policy 2010; 94: 221-29 19 Wettermark B, Pehrsson A, Juhasz-Haverinen M et al Financial incentives linked to selfassessment of prescribing patterns – a new approach for quality improvement of drug prescribing in primary care Quality in Primary Care 2009;17:179–89 20 Gustafsson LL, Wettermark B, Godman B et al The “Wise List”- A comprehensive concept to select, communicate and achieve adherence to recommendations of essential drugs in ambulatory care in Stockholm Basic & Clinical Pharmacology & Toxicology 2011; 108:224-233 21 Martikainen, J., Saastamoinen, L., Korhonen, M., et al Impact of restricted reimbursement on the use of statins in Finland Medical Care 2010; 48: 761-6 22 Godman B, Sakshaug S, Berg C, Wettermark B, Haycox A Combination of prescribing restrictions and policies to engineer low prices to reduce reimbursement costs Expert Rev Pharmacoeconomics Outcomes Res 2011; 11: 121–9 12 23 Bennie M, Godman B, Bishop I, Campbell S Multiple initiatives continue to enhance the prescribing efficiency for the proton pump inhibitors and statins in Scotland Expert Review Pharmacoeconomics and Outcomes Research 2012; 12: 125-130 24 Godman B, Burkhardt T, Bucsics A et al Impact of recent reforms in Austria on utilisation and expenditure of PPIs and lipid lowering drugs; implications for the future Expert Rev Pharmacoeconomics Outcomes Research 2009; 9:475-484 25 Voncina L, Strizrep T Croatia: 2009/2010 Pharmaceutical pricing and reimbursement reform Eurohealth 2011; 16:20-2 26 Vončina L, Strizrep T, Godman B et al Recent policies to enhance renin-angiotensin prescribing efficiency in Europe; implications for the future Expert Rev Pharmacoeconomics and Outcomes Res 2011; 11: 469-79 27 Usher-Smith J, Ramsbottom T, Pearmain H, Kirby M Evaluation of the clinical outcomes of switching patients from atorvastatin to simvastatin and losartan to candesartan in a primary care setting: years on Int J Clin Pract 2008; 62:480-4 28 Moon J, Flett A, Godman B, Grosso A, Wierzbicki A Getting better value from the NHS drug budget BMJ 2011; 342: 30-32 29 Boonen LH, van der Geest SA, Schut FT, Varkevisser M Pharmaceutical policy in the Netherlands: from price regulation towards managed competition Adv Health Econ Health Serv Res 22:53-76 (2010) 30 Schut F, Van De Ven W Effects of purchaser competition in the Dutch health system: is the glass half full or half empty? Health Economics, Policy and Law 6: 109–123 (2011) 31 Vektis Zorgthermometer Vooruitblik 2010 (Care Thermometer Prospects for 2010), Zeist: Vektis 32 Godman B, Haycox A, Schwabe U, Joppi R, Garattini S Having your cake and eating it: Office of Fair Trading proposal for funding new drugs to benefit patients and innovative companies Pharmacoeconomics 2008; 26:91-8 33 Pedersen TR, Faergeman O, Kastelein JJ et al High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial JAMA 2005; 294:2437-45 34 Weng T-C, Kao Yang Y-H, Lin S-J, Tai S-H A systematic review and meta-analysis on the therapeutic equivalnec of statins Jn Clinical Pharmacy Therapeutics 2010; 35:139-151 35 Norman C, Zarrinkoub R, Hasselström J, Godman B, Granath F, and Wettermark B Potential savings without compromising the quality of care Int J Clin Pract 2009: 63:1320–26 36 Roland M Linking Physicians' Pay to the Quality of Care - A Major Experiment in the United Kingdom NEJM 2004; 351:1448-54 37 Doran T, Fullwood C, Gravelle H, Reeves D, Kontopantelis E, Hiroeh U, Roland M Pay-forperformance programs in family practices in the United Kingdom NEJM 2006; 355:375-84 38 Vlahovic-Palcevski V, Gantumur M, Radosevic N et al Coping with changes in Defined Daily Dose in longitudinal drug consumption databases Pharm World Sci 32:125-9 (2010) 39 Eimers M, Nijpels M Report – Prescription Behaviour Monitor for General Practioners 2011 Dutch Institute for Rational Use of Medicines Postbus 3089, 3502 GB Utrecht 40 Godman B, Abuelkhair M, Vitry A, Abdu S et al Payers endorse generics to enhance prescribing efficiency; impact and future implications, a case history approach (In Press GABI) 13 41 Bero LA, Grilli R, Grimshaw JM et al Closing the gap between research and practice: an overview of systematic reviews of interventions to promote the implementation of research findings BMJ 317:465-8 (1998) 42 Barton S Using clinical evidence BMJ 322:503-4 (2001) 43 Yang YY; Lewis J; Epstein S, et al Long-term Proton Pump Inhibitor Therapy and Risk of Hip Fracture JAMA 296, 2947-53 (2006) 44 Gulmez S, Holm A, Frederiksen H et al Use of proton pump inhibitors and the risk of communityacquired pneumonia: a population-based case-control study Arch Intern Med 167, 950-5 (2007) 45 Leonard J, Marshall JK, Moavvedi P Systematic review of the risk of enteric infection in patients taking acid suppression Am J Gastroenterol 102, 2047-56 (2007) 46 Gray SL, LaCroix AZ, Larson J et al Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: results from the Women's Health Initiative Arch Intern Med 70:765-71 (2010) 47 Editorial Failing the acid test - benefits of proton pump inhibitors may not justify the risks for many users Arch Intern Med 170, 747-8 (2010) 48 Howell M, Novack V, Grgurich P et al Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium difficile infection Arch Intern Med 170, 784-90 (2010) 49 Collins R, Armitage J, Parish S, et al MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial Lancet 361:2005-16 (2003) 50 Vooght G-D, Maitland-van der Zee A-H, Schalekamp T, Mantel-Teeuwisse A, Jansen P Statin Prescribing in the Elderly in the Netherlands: A Pharmacy Database Time Trend Study Drugs Aging 27 (7): 589-596 (2010) 51 Numans ME, De Wit NJ, Dirven JAM, Hurenkamp GJB, Meijer QCM, Muris JWM, Van der Laan JR, Van Balen JAM NHG-Standaard Maagklachten (Tweede herziening) Huisarts Wet 2003;46(12): 690-700 52 Nederlands Huisartsen Genootschap (NHG) NHG Standaard Cardiovasculair risicomanagement Last update 2007, [Accessed on 2008] http://nhg.artsennet.nl/uri/? uri¼AMGATE_6059_104_TICH_R1831296 11676033 53 van de Steeg-van Gompel C, Michel Wensing M, De Smet P Implementation of a pharmacist-led intervention to enhance statin prescribing for secondary prevention in primary care: a cluster randomized trial European Journal of Preventive Cardiology 19(2): 169–176 (2011) 54 Multidisciplinaire Richtlijn Cardiovasculair risicomanagement CBO, 2006 55 Paes AH, Cornips PMJM Ontstaan en verloop van een farmacotherapie-overleg [the emergence and development of pharmacotherapeutic meetings] Pharm Weekbl 1987, 122:225-230 (1987) 56 Eimers M, de Groot J FTO peiling 2005, kwaliteit van farmacotherapieoverleg in Nederland in beeld [PTAM audit 2005, quality of pharmacotherapeutical audit meetings in the Netherlands made visible] DGV Nederlands instituut voor verantwoord medicijngebruik [DGV the Dutch Institute for the Proper Use of Medicine] 2006 57 Trietsch J, van der Weijden T, Verstappen W et al A cluster randomized controlled trial aimed at implementation of local quality improvement collaboratives to improve prescribing and test ordering performance of general practitioners: Study Protocol Implementation Science 4:6 doi:10.1186/17485908-4-6 (2009) 14 58 Smulders Y, Burgers J,T ScheltensT et al Clinical practice guideline for cardiovascular risk management in the Netherlands Netherlands Journal of Medicine 66:169-74 (2008) 59 Godman B, Wettermark B Impact of reforms to enhance the quality and efficiency of statin prescribing across 20 European countries 9th Congress EACPT 2009; 65-69 Editors Webb D and Maxwell S Medimond International Proceedings - Medimond s.t.l Via G Verdi 15/1, 1-40067 Rastignano (Bologna), Italy Volume: ISBN 978-88-7587-548-0; CD: ISBN 978-88-7587-549-7 60 Godman B, Wettermark B Trends in consumption and expenditure of proton pump inhibitors (PPIs) in 20 European countries 9th Congress EACPT 2009; 71-75 Editors Webb D and Maxwell S Medimond International Proceedings - Medimond s.t.l Via G Verdi 15/1, 1-40067 Rastignano (Bologna), Italy Volume: ISBN 978-88-7587-548-0; CD: ISBN 978-88-7587-549-7 61 Markovic-Pekovic V, Ranko Škrbić R, Godman B, Gustafsson LL Ongoing initiatives in the Republic of Srpska to enhance prescribing efficiency; influence and future direction (Submitted to Expert Review of Pharmacoeconomics and Outcomes Research) 62 Godman B, Wettermark B, Bennie M et al Enhancing prescribing efficiency through increased utilisation of generics at low prices (E)Hospital 13 (3): 28-31 (2011) Web based references 101 World Health Organisation (WHO) Guidelines for ATC classification and DDD assignment 2009 Oslo: WHO Collaborating Centre for Drug Statistics Methodology www.whocc.no [Accessed 15 May 2012] 102 World Health Organization (WHO) Introduction to Drug Utilisation Research WHO International Working Group for Drug Statistics Methodology, WHO Collaborating Centre for Drug Statistics Methodology, WHO Collaborating Centre for Drug Utilization Research and Clinical Pharmacological Services ISBN 92 156234 X (NLM classification: WB 330) Available via URL: http://www.who.int/medicines/areas/quality_safety/safety_efficacy/Drug%20utilization%20research.pdf [Accessed 15 May 2012] 103 SIGN Heart Disease – quick reference guide February 2007 Available via URL: http://www.sign.ac.uk/pdf/qrgchd.pdf [Accessed 20 May 2012] 15 ... 12: 115-124 Godman B, Shrank W, Wettermark B et al Use of generics – a critical cost containment measure for all healthcare professionals in Europe? Pharmaceuticals 2010; 3:2470-94 doi 10.3390/ph/3082470... ScheltensT et al Clinical practice guideline for cardiovascular risk management in the Netherlands Netherlands Journal of Medicine 66:169-74 (2008) 59 Godman B, Wettermark B Impact of reforms to... Ofierska-Sujkowska G, Osinska B, Herholz H et al Review of risk sharing schemes for pharmaceuticals: considerations, critical evaluation and recommendations for European payers BMC Health Services Research 2010,