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Influence of multiple initiatives in Sweden to enhance ARB prescribing efficiency following generic losartan; findings and implications for other countries
Brian Godman BSc PhD1,2,3*, Björn Wettermark MScPharm PhD3,4, Jamilette Miranda MD PhD5, Marion Bennie MSc6,7, Andrew Martin BSc8, Rickard E Malmström MD PhD9
1Institute for Pharmacological Research ‘Mario Negri’, Via Giuseppe La Masa 19, 20156 Milan, Italy. Email: [email protected]; 2Prescribing Research Group, University of Liverpool Management School, Chatham Street, Liverpool, UK L69 7ZH. 3Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-141 86, Stockholm, Sweden. Email: [email protected]. Telephone: 0046 8 585 81068. Fax: 0046 8 585 810704Centre for Pharmacoepidemilogy, Karolinska Institutet, Karolinska University Hospital Solna, SE-17176, Stockholm Sweden. Email: Bjorn. [email protected] of Healthcare Development, Public Healthcare Services Committee Administration, Stockholm County Council, Stockholm, Sweden. Email: [email protected] Institute for Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom; 7Head Drug Information Services Division, NHS National Services Scotland, Edinburgh, United Kingdom, EH12 9EB. Email: [email protected]. Telephone: +44 131 275 6432; Fax: +44 131 275 76068NHS Bury, 21 Silver Street, Bury BL9 0EN, UK. Email [email protected] of Medicine, Clinical Pharmacology Unit, Karolinska Institutet, Karolinska University Hospital Solna, SE-17176, Stockholm Sweden. Email: [email protected]
*Author for correspondence
(Accepted for publication – International Journal of Clinical Practice. Please keep CONFIDENTIAL).
What’s known
Multiple and intensive demand side measures do change physician prescribing habits All angiotensin receptor blockers are seen as equally effective for the management of
hypertension and heart failure at effective doses There is an opportunity to save considerable costs once one product in a class becomes
available as a generic by encouraging the prescribing of the generic versus existing patented products in the class
What’s new
Physicians do not readily transfer the lessons learnt regarding the prescribing of generics versus patented products in one drug class to another even if this is a similar class. This is especially the case when messages are being altered, i.e. from encouraging the prescribing of generic angiotensin converting enzyme inhibitors (ACEIs) first line versus angiotensin receptor blockers (ARBs) to preferentially prescribing ACEIs and generic ARBs
There are appreciable opportunities to save costs with the prescribing of generic losartan versus patented ARBs without compromising care. The costs of ARBs will fall further as more ARBs lose their patents
The removal of originator losartan from the reimbursement list does not appear to cause problems with appreciable prescribing of generic versus originator losartan after generics became available
Abstract
Background: Encouraging ACEIs first line versus ARBs has been a health authority focus with generic ACEIs, similar effectiveness between ACEIs and ARBs and limited coughing with ACEIs. This includes Sweden with its multiple initiatives keeping renin-angiotensin inhibitor expenditure similar between 2001 and 2007 despite appreciably increased volumes. Generic losartan was reimbursed in March 2010 providing further opportunities for the authorities in
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Sweden to save costs with all ARBs seen as similar in managing hypertension and CHF at appropriate doses. Aims: Assess changes in the utilisation of losartan versus other single ARBs after generic losartan alongside accompanying demand-side measures. In addition (i) assess changes in the price of generic losartan and single ARB expenditure over time, (ii) suggest additional programmes if needed, (iii) analyse utilisation of ARB FDCs and compare to ACEI FDCs. Methods: Retrospective observational study using an interrupted time series design. Results: Multiple demand-side measures introduced among the 21 regions in Sweden significantly enhanced the utilisation of generic losartan, growing from 26% to 27% of total ARBs (DDD basis) before generic losartan to 40% by August 2011. Losartan principally generics (97.4% by August 2011). Expenditure/ DDD for generic losartan 10% of pre-patent loss price in August 2011, reducing total single ARB expenditure by 26% by the study end despite a 16% increase in utilisation. Greater utilisation of ARB FDCs than ACEIs. This may be due to similarities in prices between single and FDC ARBs. Discussion: Multiple demand side measures appreciably enhanced ARB prescribing efficiency, mirroring other studies. No significant increase in losartan utilisation following generics in European countries not instigating specific measures. Losartan price reduction in line with expectations. Conclusion: Multiple and intensive demand side measures are needed to change physician prescribing habits, and authorities cannot rely on physicians transferring their activities from one class to another without interventions.
Key words: Generics, losartan, demand side measures, drug utilisation study, Sweden
Background
The prescribing of angiotensin receptor blockers (ARBs) as opposed to angiotensin converting enzyme inhibitors (ACEs) has been a target for health authority and health insurance company activities across Europe for some time following the availability of generic ACEIs [1-5]. This is in view of their premium prices versus generic ACEIs, no perceived differences in effectiveness between ACEIs and ARBs across indications, and prospective clinical studies showing a dry cough only occurs in approximately 10% of patients prescribed ACEIs [1-3,5,6]. However, the incidence of dry coughing may as high as 25% among selected populations including patients with heart failure who require higher doses [5]. Having said this, only 2% to 3% of patients in ACEI clinical trials discontinued their treatment due to a dry cough [1-3,7-9], and a recent ecological study in Sweden demonstrated similar outcomes in hypertensive patients in terms of reducing their blood pressure irrespective of whether they were prescribed formulary drugs such as generic ACEIs versus non-formulary patented ARBs [10].
However, health authorities and health insurance companies are aware that compliance is typically poor in patients with long term asymptomatic conditions. For instance, a meta analysis demonstrated that the average mean reported compliance rate for patients prescribed antihypertensive drugs was only 64% to 80% or more one year after initiation [11]. As a result of these findings, authorities across Europe do reimburse ARBs but only after patients are experiencing side-effect or tolerance problems with ACEIs. National and regional health authority activities to enhance the prescribing of ACEIs versus ARBs have included printed guidance, guidelines, academic detailing, active switching programmes, prescribing targets for ACEIs versus ARBs, financial incentives for physicians as well as prescribing restrictions for ARBs [1,2,5,12-17]. Prescribing restrictions typically limit the prescribing of ARBs to patients experiencing unacceptable side-effects from ACEIs, or intolerant to ACEIs. They have been introduced in Austria, Croatia, Lithuania, the Republic of Srpska and Sweden [1,2,5,14,16]. Typically the restrictions are accompanied by financial incentives and sanctions as well as other activities to encourage their adherence, reducing the potential for physicians to ignore the restrictions [1,2,12,17]. There have also been initiatives to successfully switch patients between different ARBs where there are appreciable differences in their acquisition costs to save costs [18-20].
Multiple demand-side activities have also been initiated among the counties in Sweden in recent years to enhance the prescribing of ACEIs versus ARBs. The drug budgets in Sweden are devolved to the counties (Regions), and they are responsible for staying within agreed budgets [12,13]. The multiple measures initiated include [2,10,12,13,17]:
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Educational activities including prescribing guidance, i.e. the ‘Wise List’ in Stockholm County Council, guidelines, routine benchmarking of physician prescribing habits against colleagues and against agreed guidance, and electronic prescribing support systems prompting generic ACEIs
Financial incentive schemes including devolving budgets to physician practices together with guidance on ways to enhance their prescribing efficiency. This is combined with penalties for over-budget situations, as well as direct financial incentives for physicians achieving ACEI prescribing targets
Prescribing targets including the % of ACEIs versus all ARBs (by volume)
The various initiatives limited ARB prescribing to 38% of total renin-angiotensin inhibitor drugs in Sweden in 2007 (defined daily dose – DDD basis). This combined with measures to lower the price of generics resulted in reimbursed expenditure for renin-angiotensin inhibitor drugs in Sweden similar in 2007 to that seen in 2001. This was despite a nearly doubling of the utilisation of renin-angiotensin inhibitor drugs during this period [2]. Expenditure on ARBs accounted for 84% of total renin-angiotensin inhibitor drug expenditure by the end of 2007 [2]. However, expenditure on renin-angiotensin inhibitor drugs has been increasing in the recent years [2]. This, coupled with the need for counties to save costs and enhance adherence to the guidelines recommending that patients be initiated on an ACEI, resulted in the national reimbursement agency (TLV) instigating prescribing restrictions for ARBs in 2008. This followed a full review of all drugs to treat patients with hypertension [14]. The restrictions were similar to those instigated in other European countries described earlier [2,5, 14]. A recent analysis showed that the number of patients initiated on ARBs first line decreased by 24% in the first four months following the prescribing restrictions compared with a similar period one year before restrictions, whilst those on ACEIs increased by 14% [14]. This demonstrates that prescribing restrictions can be added to other demand-side measures, and that their influence appears additive. This substantiates the findings with statins in Austria, Finland and Norway where prescribing restrictions were successfully instigated to limit the prescribing of patented versus generic statins [5,21,22].
In Sweden, there was limited utilisation of fixed dose combinations (FDCs) of renin-angiotensin inhibitor drugs in 2007 at approximately 7% of all ACEIs utilisation on a DDD basis [2], although higher utilisation of FDC ARBs. These utilisation rates for FDCs were lower than those seen in Austria, which were 33% to 35% of all ACEI and ARB utilisation in 2007 (DDD basis) [1,2]. This may reflect the need of physicians in Sweden to adequately titrate patients before initiating a FDC, different combinations being used to actually treat patients with hypertension than those seen with current FDCs, and perceived limited impact of FDCs on compliance in reality versus prescribing individual drugs separately [1,2,23].
Generic losartan was reimbursed in Sweden in March 2010. Consequently, the counties should be active in encouraging physicians to initiate patients on losartan when an ARB is indicated, as well as actively seek to switch patients on other ARBs to losartan. This is due to the envisaged low price for generic losartan versus still patented ARBs [12], total annual expenditure on single ARBs at SEK616mn (€71mn) just before generic losartan was reimbursed and losartan only accounting for 36% of total single ARB expenditure just before generic losartan. Alongside this, a Cochrane review concluded all ARBs have a statistically equivalent effect on blood pressure, which was endorsed by the National Institute for Health and Clinical Excellence (NICE) in the UK in their August 2011 guidance stating that patients with hypertension can be started on either an ACEI or low cost ARB [19, 24-26]. Alongside this, there have been no head to head trials showing any difference in effectiveness between the various ARBs for heart failure, although higher doses are typically needed to manage heart failure versus hypertension. In addition, a recent cohort study demonstrated that in patients with heart failure, higher doses of losartan (100mg/ day) were not associated with increased mortality versus candesartan, which is different for lower doses [27]. This mirrored the findings from HEAAL study which demonstrated that losartan 150mg daily reduced the rate of death or admission for heart failure for patients with heart failure compared with losartan 50mg [28]. As a result of the HEAAL, 150mg is the recommended dose within the ‘Wise List’ of Stockholm County Council [13]. Alongside this, patients in the UK have been successfully switched between ARBs without
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compromising care [18,19], although greater care may be needed when switching patients with heart failure [26,29].
The low prices for generics in Sweden have been achieved through compulsory generic substitution, apart from a limited number of situations, coupled with comprehensive IT and other systems. More recently, through the instigation of monthly pricing auctions for generics [12,30-32]. Patients though can still request the originator if wished, but they have to cover the additional costs themselves unless exempt, which is rare in practice [12,30,31].
Aim
The principal objective is to assess the extent of any changes in the utilisation of losartan versus other single patented ARBs after generic losartan was reimbursed in Sweden alongside any accompanying demand-side measures. In addition (a) assess the impact of the reforms and initiatives on the price of generic losartan over time as well as overall single ARB expenditure, (b) assess the impact of the reforms and initiatives on overall single ARB prescribing efficiency with all ARBs seen as essentially similar for hypertension and heart failure at appropriate doses, (c) suggest additional programmes that could be instigated if needed to further enhance ARB prescribing efficiency in Sweden, and (d) analyse the utilisation of ARB FDCs and compare these with the earlier situation with ACEI FDCs to suggest the rationale for any differences seen. This is because we would expect low utilisation of ARB FDCs versus single ARBs on a DDD basis in line with the situation previously seen for ACEI FDCs in Sweden. Methodology
We principally used an interrupted time series design to analyse the changes in monthly reimbursed prescriptions of all patients in Sweden contained in the national Swedish Pharmacy Register dispensed at least one ARB (C09DA01 to 09) [33] between January 2007, i.e. over 3 years before generic losartan was reimbursed in Sweden, to August 2011, some 18 months after generic losartan was reimbursed. We also conducted an observational study on the utilisation of ARB FDCs (C09DA01 to 09, C09DB01 to 05, C09DX01 to 03) [33] between January 2010 and August 2011, i.e. before generic losartan combinations were reimbursed (March 2010) to 1.5 years after. The reason for the different design is that the principle emphasis of this paper is on single ARBs with anticipated lower utilisation of ARB FDCs. The database covers all patients in Sweden, and is regularly audited to ensure the robustness of the data. Drug utilisation data is readily available to the Counties in Sweden. However more sophisticated analyses, including patient diagnosis and drug sequencing data, requires special approval. Consequently, in this first paper we will just concentrate on drug utilisation data.
ARB utilisation in both studies was assessed using DDDs, with DDDs defined as ‘the average maintenance dose of a drug when used in its major indication in adults’, as this measure is recognised as the international standard to assess utilisation patterns within and between countries [34]. 2011 DDDs were used in line with international guidance [33-36], with the WHO methodology used to calculate the DDDs for the FDCs. This was based on the principle of counting the FDC as one dose [33,34].
Serial autocorrelations of losartan DDDs were assessed in the interrupted time series design using an ARIMA model and a Box-Jenkins-Tiao strategy [37]. DDDs were plotted over time in months. The graphs were visually inspected to assess the trends or the nonstationarity of the data. Alongside this, a segmented regression analysis of the interrupted time series was used to assess the effect of the reimbursement of generic losartan and the multiple demand-side measures instigated in March 2010. Common segmented regression models were used to fit a least-squares regression line to each segment of the independent variable (time t), assuming a linear relationship between time and the outcome within each segment. The effect of the intervention (generic losartan and the multiple measures) was assessed using the model: Yt = β0 + β1 (timet = 0, 1, 2, …, 24) + β2 (intervention 1t) + β3 (time after intervention 1 t) + β4 β2 (intervention 2 t) + β5 (time after intervention 2 t)+ et, where Yt was losartan’s DDDs per month t, time is a continuous variable indicating time (in months) at time t from the start until the end of the observation period, intervention is an indicator variable for time t occurring before (t = 0 month)
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or after (t = 1 month) the reimbursement of generic losartan, and et is the error term at time t [38]. The time after reimbursement (months) is a continuous variable that counts the number of months after the intervention at time t including the demand-side measures, coded time 0 before the intervention (March 2010). The Durbin-Watson statistic was calculated to test for a serial autocorrelation of the error terms in the regression models [39]. The statistical package IBM SPSS Statistics version 19.0 was used for all analyses. A P value of <0.05 was considered significant [40].
We are confident we can undertake this type of analysis as the demand-side measures were instigated by the various Counties in Sweden in direct response to the availability of generic losartan to enhance their ARB prescribing efficiency.
Total expenditure was calculated for losartan over time as well as for originator losartan and generic losartan after generic losartan was reimbursed. This was expressed in terms of expenditure/ DDD for the various losartan preparations in Swedish Kroner (SEK). We chose to measure total expenditure as we wanted to assess the extent to which the originator company would reduce its price to limit patient co-payment with originator losartan removed from the reimbursement list once generic losartan became available; hence subject to 100% co-payment. We also chose SEK rather than Euros as we wanted to ascertain the level of price reductions without any influence of currency fluctuation rates, especially given the current financial situation with the Euro. Total ARB expenditure was also calculated to assess the influence of both the supply-side and demand-side measures on single ARB prescribing efficiency after the availability of generic losartan.
The demand-side measures have been collated into the 4Es; namely Education, Engineering, Economics and Enforcement [41]. These include [1,2,5,12-17,20,21,32]: Education, i.e. programmes that influence prescribing such as the distribution of printed
guidelines and guidance including the ‘Wise List’ in Stockholm; academic detailing and the monitoring of prescribing against agreed guidance
Engineering, i.e. organizational or managerial intervention, including prescribing and quality targets
Economics, i.e. financial incentives and interventions, including devolved budgets to physicians combined with financial incentives, additional co-payments for a more expensive drug than the current reimbursed drug (molecule or class) and financial incentives for physicians for achieving agreed prescribing targets
Enforcement, i.e. regulations including those enforced by law such as compulsory generic substitution and prescribing restrictions
A narrative review of measures instigated among the 21 Counties was undertaken by two of the co-authors (BBG and BW).
Results
Table 1 consolidates the range of initiatives instigated among the various Counties in Sweden to enhance the prescribing of generic losartan. Their intensity though may vary within individual Counties (currently 21 in Sweden).
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Table 1 – Demand side activities undertaken by the Counties in Sweden following the availability of generic losartan
Activity ExamplesEducation Changes in guidance, guidelines, and formularies to recommend
losartan first line for the management of hypertension or heart failure when an ARB is indicated
Academic detailing endorsing losartan as the ARB of choice Monitoring prescribing habits against agreed guidance on a monthly
basis and feeding the results back to physicians Benchmarking ARB prescribing patterns among colleagues and
feeding these back to physiciansEngineering Prescribing targets, e.g. % losartan as a % of all ARBs (DDD based)
Instigation of active switching programmes to change other ARBs to losartan among some counties
Economics Budget devolution combined with positive or negative financial rewards to stay within budget
Revision of physician or practice based financial incentives to now include the prescribing of losartan versus other ARBs
Enforcement There were no national prescribing restrictions for patented ARBs versus generic losartan. However, the restrictions limiting the prescribing of ARBs to second line still remained in place
Single ARB utilisation grew by 16% on an accumulated 6 monthly DDD basis by the end of the study period following the availability of generic losartan compared to the situation seen just before generic losartan was reimbursed (Table 2).
Table 2 – Accumulated 6 monthly utilisation for total single ARBs (6 months accumulated DDDs - millions) before and after the availability of generic losartan
Time from reimbursement generic losartan
Accumulated 6 months utilisation (million DDDs)
24 months before 57.7118 months before 59.8812 months before 62.326 months before 64.76Generic losartan reimbursed 66.166 months after 69.4012 months after 72.3818 months after 76.48
This growth in single ARB utilisation was driven by a significant increase in the utilisation of losartan after the availability of generic losartan (Figures 1 and 2, Table 3) coupled with the multiple interventions to enhance its utilisation versus other ARBs (Table 1), with stabilisation in the utilisation of all other single ARBs (Figure 1).
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Figure 1 – Monthly ARB utilisation January 2007 to August 2011 (DDDs)
Generic losartan reimbursed
Overall, the utilisation of losartan as a percentage of all other single ARBs (DDD basis) grew from an average of 26% to 27% from January 2010 to February 2011 to 40% by the end of the study period.
Table 3 - Parameter estimates, standard errors and P-values from the segmented regression model predicting the extent of losartan DDDs before and after generic losartan reimbursed (Coefficient variable is losartan DDDs)
Coefficientsa
Model
Unstandardized Coefficients
Standardized
Coefficients
T Sig.
95.0% Confidence Interval for B
B Std. Error Beta Lower Bound Upper Bound
1 (Constant) 2424573.721 48124.762 50.381 .000 2328004.321 2521143.120
Time 14660.481 2151.129 .303 6.815 .000 10343.924 18977.038
Reimbursement 37241.024 85167.954 .022 .437 .664 -133660.978 208143.026
After reimbursement 104201.606 6947.640 .710 14.998 .000 90260.147 118143.065
a. Dependent Variable: Losartan items dispensed
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Figure 2 – Change in utilization patterns for losartan (DDDs) over time before and after generic losartan was reimbursed and the initiation of multiple demand-side measures
Losartan was principally generic losartan, reaching 97.4% of total losartan in August 2011, helped by the removal of originator losartan from the reimbursement list in Sweden once generic losartan became available.
The utilisation of ARB FDCs as a percentage of total ARB utilisation was relatively constant from January 2010 to August 2011, averaging 24% to 26% of total ARBs (DDD basis) – Figure 3. However, the utilisation of losartan FDCs (losartan plus a diuretic) as a percentage of all ARB FDC utilisation appreciably increased after the availability of generic losartan FDCs in March 2010 (Figure 3), rising from 43% of total ARB FDCs to 51% by the end of the study period, mirroring the rise with losartan versus single ARBs.
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●Before reimbursement● After reimbursement
Figure 3 – Percentage utilisation of losartan FDC versus other ARB FDCs January 2010 to August 2011, as well as total ARB FDCs versus total ARBs (DDD basis)
Generic losartan FDCs
There was an immediate fall in the expenditure/ DDD for losartan after the availability of generic losartan in March 2010 (Figure 4). This was driven by the increasing utilisation of generic losartan versus the originator at decreasing prices, with originator losartan maintaining its price after the availability of generic losartan (Figure 4). The utilisation of originator losartan was just 2.6% of total losartan in August 2011. The price of generic losartan in August 2011 was 90% below pre-patent loss prices (expenditure/ DDD).
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Figure 4 - Total expenditure/ DDD losartan (SEK total) from January 2007 to August 2011 (total as well as originator and generic after March 2010)
Total expenditure/ DDD for generic losartan FDCs in August 2011 was 1.01SEK, 89% below the pre-patent loss price of 8.86SEK DDD. The originator price remained relatively steady after the availability of generic FDCs at 8.22SEK/ DDD in August 2011 (Figure 4). Utilisation of originator losartan FDCs was 2.9% of total losartan FDC utilisation (DDD basis) in August 2011, mirroring the situation for originator losartan versus total losartan (DDD basis).
The fall in expenditure/ DDD for generic losartan, coupled with the increasing utilisation of losartan, reduced total expenditure on single ARBs by 26% by the end of the study period (accumulated 6 monthly basis) compared with the situation just before the launch of generic losartan and the multiple demand-side initiatives (Table 1) – Table 4. This equated to SEK80mn on an accumulated 6 monthly basis 18 months after generic losartan became available (Table 4), equivalent to savings of SEK160mn on an annual basis.
Table 4 – Accumulated 6 monthly expenditure of all single ARBs (total) in SEK (mn) from January 2007 to August 2011
Time from generic losartan Total expenditure (mnSEK)24 months before 307.2918 months before 303.4812 months before 308.826 months before 306.77Launch generic 307.706 months after 244.8612 months after 233.9218 months after 227.27
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Discussion and conclusion
Multiple demand side measures in Sweden appreciably enhanced the utilisation of losartan versus other ARBs after the availability of generic losartan (Figures 1 and 2, Table 2). This includes both new patients as well as switched patients given the rate of increase in losartan utilisation versus that seen for all single ARBs combined (Figure 1, Table 1). Six monthly accumulated DDDs for losartan increased by 14.57mn DDDs (Figure 1) by the end of the study period versus the situation just before generic losartan was reimbursed. This compares with an increase of 10.32mn DDDs for all single ARBs combined (Table 2). We accept that switching rates could have been higher given the price difference between generic losartan and patented ARBs. However, other ARBs will shortly lose their patents reducing the need for active switching of all patients. Having said this, these findings confirm those from other studies that multiple intensive demand side measures do favourably change physician prescribing behaviour [42,43].
The influence of multiple demand side measures is also confirmed by recent findings among an English PCT (Bury NHS) where these measures, including active switching programmes, appreciably increased losartan utilisation versus patented ARBs [20,44]. Prior to this, there was no appreciable change in losartan utilisation versus other ARBs despite the availability of generic losartan [20,44].
However some countries and regions, including Scotland and Spain (Catelonia), chose not to instigate any demand-side measures to enhance the prescribing of generic losartan versus patented ARBs following its availability. The reasons for this included other generic ARBs will shortly be available and reimbursed in these countries, and the current quality focus was on other disease and topic areas [44, M. Bennie Personal Communication]. Not surprisingly perhaps, there was no change in the utilisation patterns for losartan following the availability of generics versus patented ARBs [44, M. Bennie Personal Communication]. This again endorses previous findings that multiple measures are needed to change physician prescribing patterns. This is even despite multiple ongoing demand-side measures in each of these two countries to enhance the prescribing of generics first line versus patented products in a class or related class [31,44-46]. These various findings substantiate the observation that there is no transfer of physician prescribing behaviour from one class to another even if the classes are closely related as on this occasion with ACEIs and ARBs, i.e.no Hawthorne effect [47-50], and that multiple interventions are needed to change physician prescribing behaviour. The Hawthorne effect in studies relates to the confounding that occurs if experimenters fail to realise how the consequences of a given subject’s performance in one area may affect activities in another area [51]. The lack of transfer of learnings from encouraging the prescribing of generic ACEIs to encouraging the prescribing of generic ARBs and ACEIs may be exacerbated in this situation by the message being more complex than simply encouraging generic drugs first line, i.e. suggesting to physicians they can now prescribe a generic ARB if wished when previously multiple demand-side measures were aimed at limiting ARB prescribing. In addition, current European and International guidelines typically still recommend ACEIs first line [6,7,13,52-54]. Having said this, NICE in the UK now endorses generic ARBs alongside generic ACEIs as first line treatment of patients with hypertension before patent protected ARBs [25,26]. We believe these findings are transferable to other classes as more standard drugs become available as generics [2,5,20,45].
We accept that we have not been able to fully evaluate the influence of the demand-side measures instigated by each County (Table 1) and have consolidated these. This is because it is difficult to undertake such activities when reporting national data. We also acknowledge that we have not evaluated individual patient data to ascertain the extent of prescribing changes in practice including any switching. This requires specific permission and is more complex to undertake. Consequently, the next stage of the research will involve ascertaining the extent and intensity of individual demand-side initiatives within each County ranked alongside their influence on subsequent prescribing of losartan in new and existing patients. The objective being to provide future guidance to the Counties in Sweden, and across Europe, on which demand side measures have the most influence on prescribing habits.
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In the meantime we believe our findings are valid, and as mentioned earlier, mirror the findings from other studies that multiple interventions are needed to successfully influence physician prescribing habits. Without such measures, there appears to be limited change in physician prescribing habits as seen with no appreciable change in the utilisation patterns of losartan in Scotland and Spain (Catalonia) following generic availability [44, M Bennie Personal Communication] or initially in Bury NHS [20,44]. Consequently, both findings provide guidance to other health authorities and health insurance agencies of the need to introduce multiple demand side measures to favourably influence future prescribing habits if they wish to save costs. In this case SEK80 million over 6 months despite a 16% increase in utilisation.
The rapid reduction in the price (expenditure/ DDD) for losartan (Figure 4) is in line with expectations. The same was seen for generic losartan FDCs. We would expect further reductions in expenditure/ DDD for both generic losartan and generic losartan FDCs with recent measures instigating monthly auctions for generics which will further reduce generic prices in Sweden [20,32]. However, this remains to be seen.
The low utilisation of originator losartan at appreciably higher expenditure/ DDD than generic losartan is also in line with expectations following the removal of originator losartan from the reimbursement list in Sweden once generic losartan became available. This coupled with significantly increased utilisation of losartan versus other ARBs (Figures 1 and 2) appreciably increased ARB prescribing efficiency. Total accumulated six monthly expenditure on single ARBs decreased by 26% (Table 4) by August 2011 compared with the situation just before generic losartan was reimbursed despite a 16% increase in their utilisation (Table 1). Prescribing efficiency is enhanced with all ARBs seen as essentially similar for the different indications at optimal dosing [18,19,24,27-29].
A surprising finding was the high utilisation of ARB FDCs (FDCs), appreciably higher than previously seen with ACEI FDCs versus all ACEIs [2]. We believe this appreciably increased utilisation is enhanced by the close proximity of expenditure/ DDD for losartan versus its FDC (Table 5), which was not true for patented ARBs, coupled with increasing budget devolution to local combined physician groups (Physician Primary Healthcare Centres). However, this remains to be substantiated.
Table 5 – Expenditure/ DDD for single ARBs and ARB FDCs in August 2011 (SEK)
ARB Exp/ DDD (SEK) Difference (SEK)Losartan single 0.62Losartan FDC 1.01 0.39Valsartan single 4.91Valsartan FDC 9.26 4.35Irbesartan single 5.37Irbesartan FDC 8.51 3.14Candesartan single 4.04Candesartan FDC 7.33 3.29
The close proximity of the prices for certain single ARBs and the corresponding FDC has persisted with ongoing measures to lower the price of generics in Sweden, e.g. in October 2012 (reimbursed price per tablet for some of the lowest priced tablets available): Losartan FDC (100mg/ 25mg hydrchlorothiazide) – 0.22SEK Losartan 100mg – 0.26SEK Valsartan FDC (now available as a generic – 160mg/ 12.5mg) – 0.46SEK Valsartan 160mg – 0.66SEK
In conclusion, multiple and intensive demand-side measures among the Counties in Sweden appreciably enhanced the utilisation of losartan versus patented ARBs once generic losartan became available. There has been no change in the utilisation pattern of losartan versus other
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ARBs in countries or regions with no active demand-side measures encouraging generic losartan. This is despite ongoing initiatives in these countries to enhance the prescribing of generics versus patented products in a class or related class. The active measures in Sweden, coupled with ongoing initiatives to lower the price of generics, appreciably enhanced ARB prescribing efficiency. As a result, provide guidance to other regions and countries seeking to further enhance their prescribing efficiency.
Financial disclosure and acknowledgements
BW and JM are employed by Stockholm County Council, Stockholm; MB is employed by NHS Scotland; AM is employed by NHS Bury. The authors have no other conflicts of interest to declare.
This work was in part supported by grants from the Karolinska Institutet, Sweden.
No writing assistance was provided for this paper.
We thank Peter Skiöld of TLV for his assistance with the reimbursed prices of ARBs alone or as FDCs in October 2012.
Author contributions
Brian Godman – Undertook the analysis and wrote the initial and final drafts Björn Wettermark and Rickard Malmstrom – critiqued the first and subsequent drafts, with
Björn Wettermark providing the drug utilisation data from the national Swedish database Marion Bennie and Andrew Martin – critiqued the first drafts including comments on
Scotland and England Jamilette Miranda – Performed the statistical analysis and critiqued the comments made
References
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