Transcript No Slide Title

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
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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
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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
Engineering
Economics
Enforcement
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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
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
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Engineering
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Economics
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Enforcement
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Selected drugs
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Selected drugs
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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
Statins
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€/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
*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
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Multiple measures for losartan
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
Withdrawal
originator
pravastatin
Reimbursed
in patients
Generic
with
simvastatin
diabetes
Atorvastatin restricted
in Austria once generic
simvastatin available
(prior authorisation).
Physician incentives to
prescribe generic
simvastatin
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DDD/ TID
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Generic simvastatin
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Originator simvastatin
Generic pravastatin
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Originator pravastatin
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Fluvastatin
15
Atorvastatin
10
Rosuvastatin
5
0
2001
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2003
2005
Year
2007
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
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Nature of restrictions
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
Physicians have to specify on the prescription
that second line treatment before atorvastatin
or rosuvastatin reimbursed,
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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
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
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
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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
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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
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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
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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 Škrbić R, Godman B et al 2012
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
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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;
[email protected]
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