Prepared by Brian Godman. Clinical Pharmacology Unit, Lyon

Transcription

1 Pan-European approaches to enhance the quality and efficiency of prescribing; what can we learn from CNC studies including the role of clinical pharmacologists? Prepared by Brian Godman Clinical Pharmacology Unit, Lyon 1

2 1. Introduction 2. Developments to optimise the managed entry of new drugs 3. Ongoing reforms to improve the quality and efficiency of prescribing of existing drugs and CNC studies 4. Role of clinical pharmacologists 5. Conclusions and recommendations 2

3 There is an increasing focus on drug expenditure across Europe which will continue As you know, healthcare expenditure represents a significant proportion of national expenditure among European countries Alongside this, European governments strive to maintain comprehensive and equitable healthcare in the face of growing pressures This has increased the focus on pharmaceutical expenditure in recent years as: Expenditure risen at between 4% to 13%/ annum in recent years outstripping other components of care although now decreasing in some countries As a result, pharmaceutical expenditure is typically the largest component of expenditure in ambulatory care Considerable opportunities to enhance the quality and efficiency of prescribing clinical pharmacologists can play a key role 3

4 Reforms will intensify to enhance the quality and efficiency of care with ongoing pressures Focus of pharmaceutical costs will continue as: Healthcare costs will rise even with current reforms - driven by ageing populations, new premium priced drugs and rising patient expectations New drugs include those for cancer estimated by one UK expert to cost up to 50billion a year within 4 years - raising UK basic tax by 15%. Often though with limited health gain Between 2007 and 2010 approximately 110 drugs lost their patents with combined global sales estimated at $50bn per year; this extends to combined global sales of $100bn/ year ( 50bn; 70bn) of drugs likely to lose their patent between 2008 and 2013 Continued variation in prescribing patterns between countries offering considerable opportunities to further enhance prescribing quality and efficiency 4 Ref: Sikora 2008, Frank 2007, Jack 2008, Garattini et al 2008, Godman, Shrank, Andersen et al 2010 and 2011

5 Reforms will intensify to enhance the quality and efficiency of care (continued) Future reforms as European governments strive to maintain comprehensive and equitable healthcare likely to include: Greater pro-activity to optimise the managed entry of new drugs, including budgeting, prescribing guidance to subpopulations where the value is greatest, and post launch follow-up. Post launch registries will play an increasing role with continuing concerns with the safety of some new drugs and value based pricing approaches Alongside this, stricter regulations for granting premium prices for new drugs as seen in France Greater refinement of risk sharing and other arrangements to enhance the value of new drugs Additional measures to enhance the quality and efficiency of prescribing of existing drugs building on the 4 Es (Education, Engineering, Economics and Enforcement) 5 Ref: Garattini et al 2008; Adamski, Godman et al 2010; Godman, Shrank, Andersen et al 2010 and 2011

6 The closer scrutiny in France in 2010 resulted in only very few drugs seen as truly innovative 6 Ref: I Durand-Zaleski, CEESTAHC 2011

7 1. Introduction 2. Developments to optimise the managed entry of new drugs 3. Ongoing reforms to improve the quality and efficiency of prescribing of existing drugs and CNC studies 4. Role of clinical pharmacologists 5. Conclusions and recommendations 7

8 Horizon Scanning activities are growing to optimise resources. Sweden provides direction Horizon Scanning, forecasting and critical drug evaluation activities are growing pre-launch across Europe especially where budgets are devolved to regions The objective is to optimise resources with funding new expensive drugs a growing challenge Processes generally start 18 to 24 months before likely launch dates. Key drugs include those likely to have a major impact on morbidity, mortality, service delivery and/ or costs Activities increasingly exist across Europe, with Stockholm County Council providing direction to others with its forecasting model incorporating input from clinical pharmacologists regarding the potential role of new drugs as well as major safety issues, e.g. Dabigatran, where they occur 8 Ref: Garattini et al 2008; Godman, Wettermark et al 2009; Wettermark, Godman, Eriksson et al 2010

9 Models to optimize managed entry include Horizon Scanning and post launch monitoring Time Industrial drug development Phase II Phase III Approval Phase IV Horizon scanning HTA pre-launch HTA post-launch Forecasting Structured introduction programmes Observational studies on effectiveness, safety and health economy 9 Ref: Wettermark, Godman, Eriksson et al 2010

10 Costs of biologicals in Stockholm County Council continues growing whilst others falling Current forecast Stockholm County (red) (msek) 10 Ref: Wettermark B Piperska Course Ljubljana 2012

11 Risk sharing arrangements are also growing to enhance funding for new expensive drugs Risk sharing schemes are growing for pharmaceuticals to help achieve two major aims. These include: Means by which payers can help control budgets especially where limited demand side measures subsequently influencing utilisation, e.g. Price: Volume agreements with pay back mechanisms, e.g. France and Italy Mechanisms by which pharmaceutical companies can enhance reimbursement/ funding for new drugs without cutting list prices, e.g. free drug and outcome guarantee schemes to improve the value proposition However, there are concerns with definitions as many different terms have been and are still being used In addition, scarcity of published data regarding the impact and outcome of current schemes to provide future guidance 11 Ref: Adamski, Godman et al 2010

12 We believed based on logic that risk sharing schemes can be divided into two models Financial/financial-based models: Price: volume agreements (PVAs) for new and existing drugs typically pay back/ rebate mechanisms if volumes and/ or expenditure exceed agreed limits for the drug, class, or overall pharmaceutical expenditure Patient access schemes involving free/ discounted drugs Price cap schemes whereby companies will cover the additional costs above agreed limits. This includes both patients and payers in the US Performance based or outcome models (with growing role of HTA): No cure, no pay schemes including rebates if drugs fail to produce desired outcomes Drugs provided free until their effectiveness is demonstrated Prices modulated if new drugs do not produce the desired patient benefits in practice (Value Based Pricing VBP) 12 Ref: Adamski and Godman 2010

13 Role of post launch registries will grow to ensure health authorities maximise value Patient registries will grow post launch to help health authorities maximise health gain with available resources/ monitor the effectiveness and safety of new drugs in routine clinical practice. Clinical pharmacologists can play a key role These include: Monitoring of prescribing against agreed guidance, e.g. Red Box System in Austria and follow-up registries in Stockholm, Sweden. This includes recent drugs such as dabigatran Monitoring the effectiveness and safety of new drugs as part of the reimbursement process (Italy) or proposed VBP in the UK Monitoring the safety of new drugs where concerns, e.g. TNF alphas for RA and psoriasis as well as natazilumab for MS following its re-launch 13 Ref: Adamski, Godman et al 2010; Papeix et al 2011; Godman, Buscics, et al 2008; Wettermark, Godman et al 2010

14 1. Introduction 2. Developments to optimise the managed entry of new drugs 3. Ongoing reforms to improve the quality and efficiency of prescribing of existing drugs and CNC studies 4. Role of clinical pharmacologists 5. Conclusions and recommendations 14

15 Ongoing measures to enhance the quality and efficiency of prescribing across Europe Ongoing developments include: Measures and initiatives to lower prices of generics as appreciable variation among countries (up to 36 fold depending on the molecule/ strength) Demand side measures to enhance the quality and efficiency of prescribing - educational, economic, engineering and enforcement activities (4 Es) especially with growing availability of generics across all classes Combining supply and demand side measures to maximise prescribing efficiency, e.g. PPIs, statins and ACEIs/ ARBs Ambulatory and hospital care physicians including clinical pharmacologists working together to maximise overall efficiency including joint formularies 15

16 Demand side measures based on 4 Es are growing in Europe to help maximise efficiency Demand side initiatives are growing across Europe to improve prescribing efficiency; 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: Economics e.g. financial incentives Education e.g. Academic detailing, benchmarking and formularies Engineering e.g. prescribing targets Enforcement legally binding arrangements and restricted prescribing initiatives Do see significant differences among European countries in their extent, nature and intensity; consequently opportunities to appreciably enhance prescribing efficiency in some countries 16 Ref: Godman, Wettermark et al 2009, Wettermark, Godman et al 2009, McGinn, Godman et al 2010

17 The definition of the 4Es and examples include: 4 E category Definition Examples Education Programmes that Examples include: influence simple distribution of printed treatment guidance prescribing through dissemination of material, which can intensive strategies such as educational outreach visits building on guidance for instance from Drugs and Therapeutic Committees be passive or active Subsequent monitoring of prescribing against agreed Engineering Economics Enforcement Organizational or managerial interventions Financial interventions (positive and negative) Regulations including those enforced by law guidance or guidelines coupled with feedback Examples include: price: volume agreements for existing drugs disease management programmes prescribing targets, e.g. the % of prescriptions for generic omeprazole versus all PPIs and % generic simvastatin versus all statins and goals for INN prescribing when this is not obligatory or enforced Examples include: patient co-payments for more expensive drugs than the current reference molecule positive and negative financial incentives for physicians devolved budgets to physicians Examples include: mandatory generic substitution in pharmacies prescribing restrictions such as prior authorisation schemes, e.g. atorvastatin in Austria; alternatively prescribing restrictions with follow-up only where concerns, e.g. Norway and Sweden 17 Ref: Wettermark, Godman et al 2009; Godman, Shrank et al 2010 and 2011

18 The Wise List has been successfully developed in Stockholm to enhance rational use of drugs The Wise List was developed in Stockholm as a means to enhance the quality of drug prescribing, with the first version published in 2001 The Wise List typically contains approximately 200 drugs for treating common diseases, with guidance for first and second line choices. It is updated each year Clear criteria for drug selection (EBM principals), coupled with trust among the physicians and public (with a separate Wise List ), has enhanced adherence, with 77% of all prescriptions in primary care adhering to the recommendations Clinical pharmacologists play a key role in compiling and amending the list. Adherence is enhanced by regular monitoring, prescribing indicators and financial incentives 18 Ref: Gustafsson, Wettermark, Godman et al 2011; Godman, Wettermark, Hoffmann et al 2009

19 A 5 point plan was developed to select first and second line drugs to enhance trust in the Wise List 5-point criteria developed by Stockholm County Council for inclusion of drugs in the Wise List Efficacy and safety based on available evidence preferably including data from randomised controlled trials as the highest level of evidence Pharmaceutical suitability formulations, strengths, and pharmacokinetic properties Efficiency mainly based on comparative reimbursed prices and the overall budget impact of the drug with the TLV currently not considering the budget impact of drugs in its deliberations Experience mainly concerned with drug safety. Recommended drugs should generally have been available for at least two years Environmental aspects if drugs are considered similar based on available evidence and similarly priced, environmental considerations guide choices. This development is seen as novel among the counties as well as other countries although the issue is of increasing concern 19 Ref: Godman, Wettermark, Hoffmann et al 2009

20 Key questions are asked about any new drug for the inclusion in the Wise List (EBM principals) 11 key questions reviewed by Expert Groups in Stockholm What was the main scientific question posed? How was patient selection conducted and diagnoses, etc.? What patients were included in the control groups and what type of study was conducted, e.g. cross-over, parallel, placebo controlled, etc.? Was the study-double-blinded, single-blinded, etc.? How was the randomisation conducted? What about the pharmacokinetics? What about concomitant medications, are these documented, valid, etc.? Are the drug effects well defined, relevant, reproducible, etc.? What about adverse events, are these well studied, described, etc.? How appropriate was the statistical design and evaluation of the results was this adequate. What about measures such as absolute risk reduction can this be calculated? What about the conclusions of the studies were these adequate, doubtful, irrelevant? 20 Ref: Wettermark, Godman et al 2008, Godman, Wettermark et al 2009

21 The Wise Drug List contains approximately 200 substances (broken down by ATC class) 21 Ref: Gustafsson, Wettermark et al 2011

22 Range of activities enhances high adherence rates to this voluntary prescribing guidance Red line refers to adherence among the 156 PHCs in 2003 Trust, academic detailing, regular monitoring, prescribing targets and financial incentives key to high adherence rates 22 Ref: Gustafsson, Wettermark et al 2011

23 Financial incentive schemes appear to be working alongside budget devolution in Sweden A variety of financial incentive models have been introduced across Sweden including Stockholm. In Stockholm this led to: Improved adherence to the Wise List of drugs Physicians identifying areas of improvement including limiting prescribing where weak evidence and safety issues - this novel inclusion has provided direction to others Savings greater than 30,000SEK/ GP for every % increase in adherence to the recommended drugs in the Wise List A recent ecological study found similar surrogate outcomes between patients prescribed formulary drugs such as generic statins and ACEis versus non-formulary drugs such as single sourced statins and ARBs (first line) Resources saved can be used to fund increased volumes and improved compliance within finite budgets 23 Ref: Wettermark et al 2008, Wettermark, Pehrsson et al 2009, Norman, Zarrinkoub et al 2009

24 Increased prescribing of higher strength simvastatin in Scotland after various measures. Use funded by low prices for generic simvastatin SIGN guidance advocating 40mg simvastatin QoF Targets Heart Protection Study 24 Ref: Bennie, Godman, Bishop et al 2012

25 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 25 Ref: Godman, Shrank, Andersen et al 2010

26 The intensity and nature of the reforms impacts on utilisation, e.g. PPIs in France and Ireland vs. England and Sweden 26 Ref: Godman, Shrank, Andersen et al 2010

27 The intensity and nature of the reforms also impacts on statin utilisation France and Ireland vs. Sweden and UK 27 Ref: Godman, Shrank, Andersen et al 2010

28 Overall considerable differences in generic prices and their utilisation - leads to considerable differences in efficiency Country Class Utilisation 2007 vs Expenditure 2007 vs /1000 inhabitants/ year in 2007 AT PPI 3.6 fold 2.1 fold Statins 2.4 fold 3% 9555 DE PPIs 3.2 fold 1.4 fold Statins 2.1 fold 54% 6833 FR* PPI 2.1 fold 38% Statin 72% 19% GB Eng PPI 2.3 fold 38% 6186 Statin 5.1 fold 20% IE PPI 2.4 fold 2.6 fold Over 60,000 Statin 7.1 fold 4.9 fold Over 60,000 SE PPI 42% 48% 5832 Statins 2.5 fold 51% 5192 * In France co-pays up to 35% for each class 28 Ref: Godman, Shrank et al 2010

29 Multiple reforms successful in Scotland to moderate RA utilisation matching prescribing restrictions in AU and HR 29 Ref: Voncina, Strizrep, Godman et al 2011

30 Intensity of reforms leading to efficiency differences versus Portugal with its limited demand side measures Reimbursed expenditure for ACEIs/ ARBs in Europe. Low cost generics in Sweden and UK enhances efficiency / i n h a b i t a n t s / y e a r AT ES GB - Scot HR PT SE Year 30 Ref: Voncina, Strizrep, Godman et al 2011

31 The ongoing measures surrounding the P4P in France also beginning to make a difference Early analysis of the pilot P4P programme (CAPI) in France indicated a positive influence on physician behaviour reversing previous trends Consequently, now extended to all GPs in France Analysis of losartan and other ARBs (single and FDCs) in France showed no change in utilisation patterns after the availability of generics to before - unlike the situation for PPIs and statins. The same for newer anti-depressants (venlafaxine, mirtazepine, duloxetine and agomelatine). In addition mirtazepine IR vs. orodispersible tablets Opportunity to help with revisions of P4P measures as more PPIs, statins and ARBs loose their patent to further enhance the quality of prescribing 31 Ref: Godman, Paterson et al In Press; Fagot, Godman, van der Erf et al (being submitted); ISPE abstract (2012)

32 1. Introduction 2. Developments to optimise the managed entry of new drugs 3. Ongoing reforms to improve the quality and efficiency of prescribing of existing drugs and CNC studies 4. Role of clinical pharmacologists 5. Conclusions and recommendations 32

33 Increasingly seeing key stakeholder groups working together to maximise efficiency Clinical pharmacologists can help health authorities and others enhance the quality and efficiency of prescribing via for instance: Providing critical drug evaluations pre-launch to give guidance on the potential value of new products at launch including any safety concerns, e.g. Stockholm with dabigatran This includes input into post launch registries and potential quality indicators, as well as help with any pharmacoeconomic analyses Ensuring contracts for drugs in hospitals increasingly take into account likely price differences in the community, e.g. helping to combat loss leaders in hospitals, e.g. Scotland Seeking to develop separate guidance on suggested common drugs ( Wise Drug List ) for out-patient hospital specialists, as well as working with key stakeholder groups to develop guidance for suggested drugs in the community as part of any networks 33 Ref: Godman, Wettermark, Bennie, Diogene et al (2012); Godman, Paterson et al In Press

34 1. Introduction 2. Developments to optimise the managed entry of new drugs 3. Ongoing reforms to improve the quality and efficiency of prescribing of existing drugs and CNC studies 4. Role of clinical pharmacologists 5. Conclusions and recommendations 34

35 Countries will need to continue learning from each other. Catalonia can provide direction European countries need to continue learning from each other to maintain the European ideals. As a result, likely to see: 35 the pace of learning accelerating with greater collaboration between countries through CNC studies. CNC studies are hard work; however, essential to assess the influence of current reforms and plan for the future greater pro-activity to optimise the managed entry of new drugs additional reforms to enhance the quality and efficiency of existing drugs building on P4P and other measures Overall, the 4E methodology provides an easily understandable methodology to describe current reforms and suggest future measures Clinical pharmacologists can play a key role with enhancing the quality and efficiency of future prescribing

36 Thank You Any Questions! marionegri.it; ki.se; 36