Pharmacoepidemiology and decision-making for health care systems

Prepared by Brian Godman

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CV Dr Brian Godman - research activities

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
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Increasing focus on drug expenditure across all sectors and countries with continuing pressures
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
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Ref: Godman, Shrank, Andersen et al 2010; Godman, Bennie et al 2012; Sermet, Andrieu, Godman et al 2010

Pharmacoepidemiology helps assess the influence of ongoing initiatives to guide future activities
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
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Pharmacoepidemiology brings together many disciplines sitting between different areas

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Ref: Godman, Shrank, Andersen et al 2010

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

Measure Education Explanation and initiatives 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 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 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) 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

Engineering

Economics

Enforcement

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

Typically European countries have introduced a range of different demand side measures. However, intensity varies
Country AT DE/ States EE ES/ regions FR* GB En GB - Scot* IE IT/ Regions LT HR NO PO PT RS SE SI TR
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Education

Engineering

Economics

Enforcement

Selected drugs Selected drugs

Ref: Godman, Shrank, Andersen et al 2010

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

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Ref: Godman, Shrank, Andersen et al 2010

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

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Ref: Godman, Shrank et al 2010

Differences in intensity of supply and demand side reforms impacted on PPI prescribing efficiency
% change for PPIs in Europe - 2007 vs. 2001 (DDDs)

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Ref: Godman, Shrank, Andersen et al 2011

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

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Ref: Godman, Shrank et al 2010

Differences in intensity and nature of the reforms led to considerable differences in prescribing efficiency - statins % change for statins in Europe - 2007 vs. 2001 (DDDs)

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Ref: Godman, Shrank et al 2011

Intensity and nature of reforms led to considerable differences in expenditure across Europe PPIs and statins
Class PPIs /1000 inhabitants/ year in 2007 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 Republic of Ireland over 60,000* France - 14,896*** Spain (Catalonia) - 14,174 England - 13,439**** Portugal 10,031 Germany - 6,833** Sweden - 5192

Statins

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

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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

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Ref: Adapted from Voncina, Strizrep et al 2011

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

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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)

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Ref: Godman, Wettermark, Miranda et al 2013

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

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Ref: Bennie, Bishop, Godman et al In Press

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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
Generic losartan reimbursed Multiple measures for losartan

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

Care needed when introducing prescribing restrictions as expectations may not be fully realised
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)
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Ref: Godman, Sakshaug et al 2011; Voncina, Strizrep, Godman et al 2011; Godman, Persson et al (re-submitted)

Generic pravastatin

Restrictions on atorvastatin Reimbursed in patients with diabetes

Withdrawal originator pravastatin

Generic simvastatin

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

45 40 35
Generic simvastatin Originator simvastatin Generic pravastatin Originator pravastatin

DDD/ TID

30 25 20 15 10 5 0 2001 2003 Year 2005 2007

Fluvastatin Atorvastatin Rosuvastatin

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However nature of follow-up of restrictions led to difference in the utilisation of patented statins
Country and statins AT (Austria) A only R restricted from outset FI (Finland) Atorvastatin and Rosuvastatin NO (Norway) only A as R not reimbursed during study Nature of restrictions
Physicians need the permission of the Chief Medical Officer of the patients Social Insurance Fund for atorvastatin to be reimbursed, otherwise 100% co-payment Physicians have to specify on the prescription that second line treatment before atorvastatin or rosuvastatin reimbursed, Specific permission only if physicians wished to prescribe lower strength atorvastatin (10 and 20mg) Otherwise physicians trusted just to write rationale for atorvastatin in patients notes

Overall change in utilisation A + R 31.6% in 2003 to 10.9% in 2007

% change over time 66% reduction

44.2% before restrictions to 18.3% 1.2 years after 46.2% in 2004 (full year before restrictions) to 26.2% in 2008

59% reduction 44% reduction

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Ref: Godman, Sakshaug et al 2011

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

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Ref: Voncina, Strizrep, Godman et al 2011

Generic omeprazole launched

Generic lansoprazole launched

Prescribing restrictions for esomeprazole

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

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Ref: Godman, Sakshaug et al 2011

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

Prescribing restrictions Duloxetine

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

Pharmacoepidemiology helps assess the influence of ongoing initiatives to guide future activities
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 acidrelated stomach disorders, hypertension or hypercholesterolaemia
Lastly, drug utilisation and expenditure classes help focus attention on potential future initiatives, e.g. pricing of reninangiotensin FDCs in Serbia 31 Brazil

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

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Ref: Godman, Bennett, Bennie et al 2012

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

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Ref: Godman, Bucsics, Burkhardt et al 2013

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

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Ref: Kalaba, Godman et al 2012

In conclusion with established drugs ..

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. reninangiotensin 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
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Ref: Garuoliene, Godman et al 2011, Markovic-Pekovic V, Ranko krbi 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 GB290mn higher in Scotland in 2010 for 5.2mn population
Generic simvastatin reimbursed

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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

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

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

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

Thank You Any Questions!

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

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