Pharmacoepidemiology and decision-making for health care systems Prepared by Brian Godman

1. Pharmacoepidemiology and decision-making for health care systems Prepared by Brian Godman

2. 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

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

5. 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

6. Pharmacoepidemiology brings together many disciplines sitting between different areas Ref: Godman, Shrank, Andersen et al 2010

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

9. The definition of the 4Es and examples include: Ref: Wettermark, Godman et al 2009; Godman, Wettermark, Bishop et al 2012

10. Typically European countries have introduced a range of different demand side measures. However, intensity varies Ref: Godman, Shrank, Andersen et al 2010

11. Each European country has different approaches to the pricing of generics. However, can be consolidated under 3 headingsIn addition, great differences in GDP between the different EU countries Ref: Godman, Shrank, Andersen et al 2010

12. Intensity and nature of the reforms impacts on PPI utilisation patterns post generic omeprazole Ref: Godman, Shrank et al 2010

13. 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

14. 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

15. 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) Ref: Godman, Shrank et al 2011

16. Intensity and nature of reforms led to considerable differences in expenditure across Europe – PPIs and 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 Ref: Godman, Shrank et al 2011; Godman, Wettermark and Bishop et al 2012

18. 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

19. 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

21. 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

22. 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

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

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

26. Generic pravastatin Atorvastatin restricted in Austria once generic simvastatin available (prior authorisation). Physician incentives to prescribe generic simvastatin Withdrawal originator pravastatin Restrictions on atorvastatin Reimbursed in patients with diabetes Generic simvastatin

27. However nature of follow-up of restrictions led to difference in the utilisation of patented statins Ref: Godman, Sakshaug et al 2011

28. Greater scrutiny of patients in Croatia with potential fines enhances utilisation of ACEIs Ref: Voncina, Strizrep, Godman et al 2011

29. Esomeprazole restriction less influence in Norway as first PPI prescription/ referral via specialist Prescribing restrictions for esomeprazole Generic omeprazole launched Generic lansoprazole launched Ref: Godman, Sakshaug et al 2011

30. Prescribing restrictions limiting duloxetine to refractory patients in Sweden appreciably enhanced the utilisation of venlafaxine but limited influence on duloxetine as depression complex disease Prescribing restrictions Duloxetine Generic venlafaxine Ref: Godman, Persson et al – re-submitted for publication

31. 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 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

32. 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

33. 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

35. 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

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

37. 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

40. 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

41. 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

42. Thank You Any Questions! Brian.Godman@ ki.se; mail@briangodman.co.uk