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Pharmacoepidemiology anddecision-making for health care

systemsPrepared 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, atypicalantipsychotics, PPIs and statins alongside learnings

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

Ways to improve utilisation of existing drugs to optimisethe 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 withpayers/ 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 asignificant 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 drugsincluding biologicals and stricter management targets

Pharmaceutical expenditure is now the largest/ equal largestcost 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 withcontinuing pressure on resources - through greater prevalenceof chronic diseases and new expensive drugs

Increasing focus on drug expenditure across allsectors 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 includemeasures to enhance the utilisation of low cost generics versusoriginators and patented products in a class/ related class

Aggregated cross national comparative (CNC)

pharmacoepidemiology studies can help authorities assess theinfluence/ impact of current measures (demand-side initiativesvia 4Es) to better plan for the future if you do notmeasure it how can you manage it

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

Pharmacoepidemiology helps assess the influenceof ongoing initiatives to guide future activities

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Pharmacoepidemiology brings together manydisciplines sitting between different areas

Ref: Godman, Shrank, Andersen et al 2010

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Demand side initiatives are growing across Europe to improveprescribing efficiency for established drugs; increasingly intandem with supply side measures

Demand side initiatives can be collated under 4 Es wellaccepted by payers and endorsed in publications: Educatione.g. Academic detailing, benchmarking,

guidelines and formularies Economicse.g. financial incentives Engineeringe.g. prescribing targets Enforcementlegally binding arrangements and

prescribing restrictions (not applicable in Scotland)

Do see appreciable differences among European countries intheir extent, nature and intensity; consequently opportunitiesfor considerable savings among some countries

Demand side measures based on 4 Es aregrowing 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 intensivestrategies 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. UKo Information and other campaigns among patients to address any fears about

the effectiveness and/ or safety of generics including speaking with patientsto address any fears, e.g. France

o

Physicians and pharmacists developing a list of potentially non-substitutableproducts where there are concerns with bioequivalence as well as thetherapeutic 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 ifphysicians 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 mandatorygeneric 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 ofdifferent demand side measures. However, intensity varies

Country Education Engineering Economics Enforcement

AT DE/ States EE ES/ regions FR* GBEn GB - Scot* IE IT/ Regions LT HR NO PO PT RS Selected drugsSE SI Selected drugsTR


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

In addition, great differences in GDP between the differentEU countries


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

Ref: Godman, Shrank et al 2010

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

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


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


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


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

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Intensity and nature of reforms led to considerabledifferences 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 Irelandover 60,000* Austria -19,299** France15,194*** Portugal15,197 Germany -13,864** Spain (Catalonia) -12,796 England -6186 Sweden -5832

Statins Republic of Irelandover 60,000* France -14,896*** Spain (Catalonia) -14,174 England -13,439**** Portugal10,031

Germany -6,833** Sweden -5192

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

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Th f d d id l li i d

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The range of demand-side measures also limitedARB utilisation in Scotland versus Portugal,matching the influence of prescribing restrictionsfor ARBs in Austria and Croatia

Ref: Adapted from Voncina, Strizrep et al 2011

As a result limited any increase in expenditure on renin

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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 appreciablyincreasing utilisation in all countries

Ref: Adapted from Voncina, Strizrep et al 2011

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M lti l d d id th C ti i

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Multiple demand side measures among the Counties inSweden including guidelines, benchmarking, formularies,prescribing targets, financial incentives and therapeuticswitching programmes significantly increased losartanutilisation post generics (March 2010)

Ref: Godman, Wettermark, Miranda et al 2013

However no change in the utilisation of losartan

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However, no change in the utilisation of losartanfollowing generics in Scotland even with measuresencouraging generic ACEIs (exacerbated by a morecomplex message). This suggests no spill over effect

Ref: Bennie, Bishop, Godman et al In Press

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No change initiall in the tilisation of losa tan follo ing

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Multiple measures for losartanGeneric losartan reimbursed

No change initially in the utilisation of losartan followinggenerics in NHS Bury. However, significant and substantialchange following multiple measures including therapeuticswitching 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 restrictionsintroduced in Sweden for duloxetine had limited impact on itssubsequent utilisation as complex disease area; however,significantly increased utilisation of venlafaxine

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

Care needed when introducing prescribingrestrictions 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)

Generic

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Genericpravastatin

Genericsimvastatin

Restrictionson

atorvastatin

Withdrawaloriginator

pravastatin

0

5

1015

20

25

30

35

40

45

2001 2003 2005 2007

Year

DDD/TID

Generic simvastatin

Originator simvastatin

Generic pravastatin

Originator pravastatin

Fluvastatin

AtorvastatinRosuvastatin

Reimbursedin patients

withdiabetes

Atorvastatin restrictedin Austria once genericsimvastatin available(prior authorisation).Physician incentives toprescribe genericsimvastatin

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

Ref: Godman, Sakshaug et al 2011

Country andstatins

Nature of restrictions Overall change inutilisation A+ R % changeover time

AT (Austria)AonlyRrestricted fromoutset

Physicians need the permission of the ChiefMedical Officer of the patients SocialInsurance Fund for atorvastatin to bereimbursed, otherwise 100% co-payment

31.6% in 2003 to10.9% in 2007

66%reduction

FI (Finland)Atorvastatin andRosuvastatin

Physicians have to specify on the prescriptionthat second line treatment before atorvastatin

or rosuvastatin reimbursed,

44.2% beforerestrictions to 18.3%

1.2 years after

59%reduction

NO (Norway)only Aas Rnot reimbursedduring study

Specific permission only if physicianswished to prescribe lower strengthatorvastatin (10 and 20mg)

Otherwise physicians trusted just to writerationale for atorvastatin in patients notes

46.2% in 2004 (fullyear before

restrictions) to 26.2%in 2008

44%reduction

Greater scrutiny of patients in Croatia with

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Greater scrutiny of patients in Croatia withpotential fines enhances utilisation of ACEIs

Ref: Voncina, Strizrep, Godman et al 2011

Esomep a ole

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Genericomeprazolelaunched

Genericlansoprazolelaunched

Prescribingrestrictions foresomeprazole

Esomeprazolerestriction lessinfluence in Norway asfirst 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 patientsin Sweden appreciably enhanced the utilisation of venlafaxine butlimited influence on duloxetine as depression complex disease

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

Ph id i l h l th i fl

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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 inrelated classes

The influence of prescribing restrictions is affected by theirnature/ follow-up. Consequently, care is needed whenintroducing 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 antipsychoticdrugs, as they are complex disease areas to treat versus acid-

related stomach disorders, hypertension orhypercholesterolaemia

Lastly, drug utilisation and expenditure classes help focusattention on potential future initiatives, e.g. pricing of renin-

angiotensin FDCs in Serbia

Pharmacoepidemiology helps assess the influenceof ongoing initiatives to guide future activities

Limited demand side measures meant no

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Limited demand-side measures meant nochange in risperidone utilisation followinggenerics across Europe exacerbated by thecomplexity of treating schizophrenia and BPD

Ref: Godman, Bennett, Bennie et al 2012

Si il tt i A t i d S i

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

Ref: Godman, Bucsics, Burkhardt et al 2013

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Reference pricing being contemplated in Serbia with

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Reference pricing being contemplated in Serbia withthe recent increase in expenditure on renin-angiotensin drugs driven by comparatively higher costsof 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 changephysician 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 toeffect a change in physician prescribing habits. This occurseven when the classes are closely related, e.g. renin-

angiotensin inhibitor drugs with losartan

Care is needed when introducing prescribing restrictions astheir nature, intensity and follow-up can appreciably influencesubsequent prescribing

The population size of a country is not a barrier to introducingmultiple initiatives as seen with the plethora of measuresintroduced in Lithuania (population 3.4mn) and Republic ofSrpska (population 1.43mn) in recent years to improve helpimprove health within resource constrained environments

In conclusion with established drugs ..

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

Multiple measures to increase simvastatin use at 3% of the

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Multiple measures to increase simvastatin use at 3% of theoriginator price meant no increase in expenditure (7%) despite 6fold increase in utilisation. Without these, statin expenditureGB290mn 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

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y, p j gwith safety data to point out potential areas ofconcern in European countries with the prescribing ofantipsychotics (APs) and antihistamines, e.g. APs

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

The ARITMO project combines drug utilisation and

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p j gsafety data to point out potential areas of concern inEuropean countries with the prescribing ofantipsychotics (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;[email protected]

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