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Pharmacoepidemiology and decision-making for health care

systems

Prepared by Brian Godman

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PhD research activities initially across Austria, France, Germany, Italy, Poland, Sweden and UK regarding measures to:

Enhance the prescribing of generics first line and drive down prices to enhance prescribing efficiency

Optimise the managed entry of new drugs Extended across Europe and globally researching:

Classes - including ACEIs, ARBs, antidepressants, atypical antipsychotics, PPIs and statins alongside learnings

Potential risk sharing and other activities to optimise reimbursement/ funding for new premium priced drugs

Ways to improve utilisation of existing drugs to optimise the quality and efficiency of prescribing - based on 4Es

More recently, researching ICT in Fragile States Over 50 peer reviewed publications in the past 5 years with

payers/ advisers/ academics in Australia, Canada, Europe, Middle East, US and S. America

CV – Dr Brian Godman - research activities

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As you are aware, healthcare expenditure represents a significant proportion of national expenditure

Focus on pharmaceutical expenditure has grown as: Ambulatory care drug expenditure rose by an averaging of 50%

in real terms between 2000 and 2009 among OECD countries - driven by demographics, new expensive drugs including biologicals and stricter management targets

Pharmaceutical expenditure is now the largest/ equal largest cost component in ambulatory care and growing in hospitals

Considerable opportunities to enhance prescribing efficiency through e.g. increasing use of generics at lower prices

Led to multiple reforms across countries, especially in Europe, to help maintain comprehensive and equitable healthcare with continuing pressure on resources - through greater prevalence of chronic diseases and new expensive drugs

Increasing focus on drug expenditure across all sectors and countries with continuing pressures

Ref: Godman, Shrank, Andersen et al 2010; Godman, Bennie et al 2012; Sermet, Andrieu, Godman et al 2010

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Multiple reforms have been instigated across countries to enhance the quality and efficiency of prescribing. These include measures to enhance the utilisation of low cost generics versus originators and patented products in a class/ related class

Aggregated cross national comparative (CNC) pharmacoepidemiology studies can help authorities assess the influence/ impact of current measures (demand-side initiatives via 4Es) to better plan for the future – ‘if you do not measure it – how can you manage it’

Lessons learnt include: (i) need for multiple initiatives to favourably change prescribing habits – with no ‘spill over’ effect even in related classes, (ii) the influence of prescribing restrictions is affected by their nature/ follow-up, (iii) timing of restrictions is important, (iv) more difficult to effect change in some classes, e.g. antidepressants and antipsychotic drugs

Pharmacoepidemiology helps assess the influence of ongoing initiatives to guide future activities

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Pharmacoepidemiology brings together many disciplines sitting between different areas

Ref: Godman, Shrank, Andersen et al 2010

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Demand side initiatives are growing across Europe to improve prescribing efficiency for established drugs; increasingly in tandem with supply side measures

Demand side initiatives can be collated under 4 ‘E’s – well accepted by payers and endorsed in publications:

Education – e.g. Academic detailing, benchmarking, guidelines and formularies

Economics – e.g. financial incentives Engineering – e.g. prescribing targets Enforcement – legally binding arrangements and

prescribing restrictions (not applicable in Scotland)

Do see appreciable differences among European countries in their extent, nature and intensity; consequently opportunities for considerable savings among some countries

Demand side measures based on 4 Es are growing in Europe to help conserve resources

Ref: Wettermark, Godman et al 2009, Godman, Shrank et al 2010 and 2011; Godman, Bennie et al 2012

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The definition of the 4Es and examples include:

Ref: Wettermark, Godman et al 2009; Godman, Wettermark, Bishop et al 2012

Measure Explanation and initiatives Education Activities range from simple distribution of printed material to more intensive

strategies including academic detailing and monitoring of prescribing habits Examples include:

o Education of trainee doctors in medical schools to prescribe by INN (International Non-Proprietary Name), e.g. UK

o Information and other campaigns among patients to address any fears about the effectiveness and/ or safety of generics including speaking with patients to address any fears, e.g. France

o Physicians and pharmacists developing a list of potentially non-substitutable products where there are concerns with bioequivalence as well as the therapeutic equivalence of generics, e.g. Sweden and UK

Engineering This refers to organisational or managerial interventions Examples include substitution targets for certain drugs in community pharmacies if

physicians are still prescribing the originator, e.g. France Economics This includes financial incentives for physicians, patients and pharmacists, e.g.:

Higher co-payments for patients if they wish to receive a more expensive product than the current referenced price molecule, e.g. Finland, Sweden

Devolution of drug budgets to physicians with sanctions for over budget situations (e.g. Germany, Sweden and UK)

Enforcement This includes regulations by law such as mandatory INN prescribing or mandatory generic substitution at pharmacies apart from a limited number of agrees situations, e.g. Lithuania and Sweden

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Typically European countries have introduced a range of different demand side measures. However, intensity varies

Country Education Engineering Economics Enforcement AT √ √ √ DE/ States √ √ √ √ EE √ √ √ √ ES/ regions √ √ √ √ FR* √ √ √ √ GB – En √ √ √ GB - Scot* √ √ √ IE √ IT/ Regions √ √ √ √ LT √ √ √ √ HR √ √ √ √ NO √ √ PO √ √ √ PT √ √ √ √ RS √ Selected drugs SE √ √ √ √ SI √ √ Selected drugs TR √

Ref: Godman, Shrank, Andersen et al 2010

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Each European country has different approaches to the pricing of generics. However, can be consolidated under 3 headings

In addition, great differences in GDP between the different EU countries

Ref: Godman, Shrank, Andersen et al 2010

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Intensity and nature of the reforms impacts on PPI utilisation patterns post generic omeprazole

Ref: Godman, Shrank et al 2010

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Differences in intensity of supply and demand side reforms impacted on PPI prescribing efficiency

% change for PPIs in Europe - 2007 vs. 2001 (DDDs)

Ref: Godman, Shrank, Andersen et al 2011

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Intensity and nature of the reforms impacts on utilisation, e.g. statins in Ireland and France vs. Sweden and UK

Ref: Godman, Shrank et al 2010

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Differences in intensity and nature of the reforms led to considerable differences in prescribing efficiency - statins

Ref: Godman, Shrank et al 2011

% change for statins in Europe - 2007 vs. 2001 (DDDs)

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Intensity and nature of reforms led to considerable differences in expenditure across Europe – PPIs and statins

Ref: Godman, Shrank et al 2011; Godman, Wettermark and Bishop et al 2012

Class €/1000 inhabitants/ year in 2007 PPIs Republic of Ireland – over €60,000*

Austria - €19,299** France – €15,194*** Portugal – €15,197 Germany - €13,864** Spain (Catalonia) - €12,796 England - €6186 Sweden - €5832

Statins Republic of Ireland – over €60,000* France - €14,896*** Spain (Catalonia) - €14,174 England - €13,439**** Portugal – €10,031 Germany - €6,833** Sweden - €5192

*Population in Ireland with subsidised health care with greater morbidity than the total population. **Total expenditure.***Excludes 35% co-payments. ****GPs in England are incentivised to reach target lipid levels which appreciably increased statin utilisation versus other European countries

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The range of demand-side measures also limited ARB utilisation in Scotland versus Portugal, matching the influence of prescribing restrictions for ARBs in Austria and Croatia

Ref: Adapted from Voncina, Strizrep et al 2011

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As a result, limited any increase in expenditure on renin-angiotensin inhibitor drugs in recent years in Austria, Croatia and Scotland vs. Portugal despite appreciably increasing utilisation in all countries

Ref: Adapted from Voncina, Strizrep et al 2011

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Multiple demand side measures among the Counties in Sweden including guidelines, benchmarking, formularies, prescribing targets, financial incentives and therapeutic switching programmes significantly increased losartan utilisation post generics (March 2010)

Ref: Godman, Wettermark, Miranda et al 2013

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However, no change in the utilisation of losartan following generics in Scotland even with measures encouraging generic ACEIs (exacerbated by a more complex message). This suggests no ‘spill over’ effect

Ref: Bennie, Bishop, Godman et al In Press

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Multiple measures for losartanGeneric losartan reimbursed

No change initially in the utilisation of losartan following generics in NHS Bury. However, significant and substantial change following multiple measures including therapeutic switching – this also confirms no ‘spill over’ effect

Ref: Martin, Godman et al (re-submitted for publication); Godman, Bennie et al 2012

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Differences in the nature and follow up of prescribing restrictions also important to effect change: Patented statins versus generics in Austria, Finland and Norway Renin-angiotensin inhibitor drugs Austria and Croatia. Both

introduced prescribing restrictions for ARBs as higher requested price than ACEIs with no efficacy difference

Esomeprazole (patented PPI) versus generic PPIs in Norway

The disease area is also important. Prescribing restrictions introduced in Sweden for duloxetine had limited impact on its subsequent utilisation as complex disease area; however, significantly increased utilisation of venlafaxine

Timing is also important – limited impact of prescribing restrictions for patented statins in Sweden some 6 years + after multiple measures among the Counties (Regions)

Care needed when introducing prescribing restrictions as expectations may not be fully realised

Ref: Godman, Sakshaug et al 2011; Voncina, Strizrep, Godman et al 2011; Godman, Persson et al (re-submitted)

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Generic pravastatin

Generic simvastatin

Restrictions on

atorvastatin

Withdrawal originator

pravastatin

0

5

10

15

20

25

30

35

40

45

2001 2003 2005 2007

Year

DD

D/

TID

Generic simvastatin

Originator simvastatin

Generic pravastatin

Originator pravastatin

Fluvastatin

Atorvastatin

Rosuvastatin

Reimbursed in patients

with diabetes

Atorvastatin restricted in Austria once generic simvastatin available (prior authorisation). Physician incentives to prescribe generic simvastatin

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However nature of follow-up of restrictions led to difference in the utilisation of patented statins

Ref: Godman, Sakshaug et al 2011

Country and statins

Nature of restrictions Overall change in utilisation ‘A’ + ‘R’

% change over time

AT (Austria) – ‘A’ only – ‘R’ restricted from outset

Physicians need the permission of the Chief Medical Officer of the patient’s Social Insurance Fund for atorvastatin to be reimbursed, otherwise 100% co-payment

31.6% in 2003 to 10.9% in 2007

66% reduction

FI (Finland) – Atorvastatin and Rosuvastatin

Physicians have to specify on the prescription that second line treatment before atorvastatin or rosuvastatin reimbursed,

44.2% before restrictions to 18.3%

1.2 years after

59% reduction

NO (Norway) – only ‘A’ as ‘R’ not reimbursed during study

Specific permission only if physicians wished to prescribe lower strength atorvastatin (10 and 20mg)

Otherwise physicians trusted just to write rationale for atorvastatin in patient’s notes

46.2% in 2004 (full year before

restrictions) to 26.2% in 2008

44% reduction

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Greater scrutiny of patients in Croatia with potential fines enhances utilisation of ACEIs

Ref: Voncina, Strizrep, Godman et al 2011

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Generic omeprazole launched

Generic lansoprazole launched

Prescribing restrictions for esomeprazole

Esomeprazole restriction less influence in Norway as first PPI prescription/ referral via specialist

Ref: Godman, Sakshaug et al 2011

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Generic venlafaxine Prescribing restrictions Duloxetine

Prescribing restrictions limiting duloxetine to refractory patients in Sweden appreciably enhanced the utilisation of venlafaxine but limited influence on duloxetine as depression complex disease

Ref: Godman, Persson et al – re-submitted for publication

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Lessons learnt include: There is a need for multiple initiatives to favourably change

prescribing habits – with no apparent ‘spill over’ effect even in related classes

The influence of prescribing restrictions is affected by their nature/ follow-up. Consequently, care is needed when introducing these else authorities may be disappointed with the outcome

The timing of introducing prescribing restrictions is also important to maximise their impact

It is more difficult to effect change in physician prescribing habits in some classes, e.g. antidepressants and antipsychotic drugs, as they are complex disease areas to treat versus acid-related stomach disorders, hypertension or hypercholesterolaemia

Lastly, drug utilisation and expenditure classes help focus attention on potential future initiatives, e.g. pricing of renin-angiotensin FDCs in Serbia

Pharmacoepidemiology helps assess the influence of ongoing initiatives to guide future activities

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Limited demand-side measures meant no change in risperidone utilisation following generics across Europe – exacerbated by the complexity of treating schizophrenia and BPD

Ref: Godman, Bennett, Bennie et al 2012

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Similar patterns seen in Austria and Spain (Catalonia) where generic risperidone was launched prior to the start of the CNC study - confirming the complexity of disease area, e.g. Austria

Ref: Godman, Bucsics, Burkhardt et al 2013

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Reference pricing being contemplated in Serbia with the recent increase in expenditure on renin-angiotensin drugs driven by comparatively higher costs of FDCs with limited clinical justification for their use over combining single agents and higher prices

Ref: Kalaba, Godman et al 2012

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Multiple-demand side measures are needed to change physician prescribing habits. This can result in an appreciable increase in prescribing efficiency, e.g. statins in Scotland

There appears to be no ‘spill over’ effect between classes to effect a change in physician prescribing habits. This occurs even when the classes are closely related, e.g. renin-angiotensin inhibitor drugs with losartan

Care is needed when introducing prescribing restrictions as their nature, intensity and follow-up can appreciably influence subsequent prescribing

The population size of a country is not a barrier to introducing multiple initiatives as seen with the plethora of measures introduced in Lithuania (population 3.4mn) and Republic of Srpska (population 1.43mn) in recent years to improve help improve health within resource constrained environments

In conclusion with established drugs ..

Ref: Garuoliene, Godman et al 2011, Markovic-Pekovic V, Ranko Škrbić R, Godman B et al 2012

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Multiple measures to increase simvastatin use at 3% of the originator price meant no increase in expenditure (7%) despite 6 fold increase in utilisation. Without these, statin expenditure GB£290mn higher in Scotland in 2010 for 5.2mn population

Generic simvastatin reimbursed

Ref: Bennie, Godman, Bishop et al 2012; Godman, Bennie et al 2012

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Finally, the ARITMO project combines drug utilisation with safety data to point out potential areas of concern in European countries with the prescribing of antipsychotics (APs) and antihistamines, e.g. APs

Ref: Raschi, Poluzzi, Godman et al 2012 and In Press (abstracts) and being prepared for submission

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The ARITMO project combines drug utilisation and safety data to point out potential areas of concern in European countries with the prescribing of antipsychotics (APs) and antihistamines, e.g. APs

Ref: Raschi, Poluzzi, Godman et al 2012 and In Press (abstracts) and being prepared for submission

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Thank You

Any Questions!

Brian.Godman@ ki.se; mail@briangodman.co.uk