1. EHC Workshop on Economics and HTA’s for EU Member Organisations September 20 th, 2014 Keith Tolley Director Tolley Health Economics Ltd keith@tolleyhealtheconomics.com 1

2. Disclaimer – my opinions 2

3. These are economically challenging times for health care payers! 3

4. Pressures on the payers… Drug expenditures continue to rise New drugs are rarely cost saving New drugs for previously untreated conditions Ageing, obesity, etc Growing patient awareness Budgets for health care becoming even more constrained Always been constrained - Economic austerity of last few years meaning becoming even more constrained 4

5. In economically challenged times new innovative therapies need to represent good value for money! Need to provide the patient, health service and societal benefits at a cost that payers are willing to pay The more an unmet need is met the more payers may be willing to pay! This willingness to pay can be expected to vary across healthcare payers in Europe (depending on budgets and health care priorities) 5

6. Innovation is about addressing an unmet need! Source: Morgan et al. 2008, Open Medicine 2 (1):E4-7 “Neither newness nor effectiveness separately or together constitute innovation” 6

7. COST Health Benefit RISK Clinical Benefit GETTING MARKETING AUTHORISATION GETTING MARKET ACCESS

8. Not all drugs that get marketing authorisation get market access. CONTROLLED by: ………..restrictions on the price for public reimbursement ……….limiting the level of reimbursement ……….controlling market access through Health Technology Assessment (HTA) – UK situation Market access controls

9. Health Technology Assessment Health Technology Assessment (HTA) is “a form of policy research that systematically examines the short-and long- term consequences, in terms of health and resource use, of the application of a health technology” (Henshall et al., 1997) HTA has been used as a tool across many countries to help national and regional authorities and payers assess the added value new pharmaceuticals bring: To determine reimbursement and/or price at market access To inform clinical guidance/prescribing HTA in Europe is co-ordinated through organisations such as EUnetHTA 9

10. National decision makers and local payers 10 Decision makers: National reimbursement and HTA bodies e.g. NICE in UK, TLV in Sweden, IQWiG in Germany, AHTAPol in Poland Local Payers: Local payers are health authorities and hospitals

11. What are health care decision makers and payers willing to pay for ? 11 Not just newness, or new mechanism of action alone, or new formulation! But…… The health care benefits a drug brings: Clinical benefits Survival improvements Quality of life (QoL) improvements Healthcare resource savings: Reductions in hospital inpatient use Significant improvements in the quality of care Wider Societal benefits: Quality of life benefits for family members and caregivers Improved economic and social returns

12. What does a payer want to know? What offers best value – payers want value based assessments? What can we afford? Perspective and what is included within “value” is important and varies by country/type of payer: In Sweden a societal perspective is adopted In UK a healthcare and social service perspective is adopted, but moving more ‘societal’ Regional payers (Spain, Italy) concerned with budget impact, cost offsets Local payers focussed on affordability in every country Other factors could be important: orphan, unmet need, clinician and patient demand 12

13. Assessments of cost-effectiveness The QALY is growing in use around Europe as the ‘standard’ measure of the health benefits (and hence value) of new pharmaceutical interventions Long established in UK and several other European countries More recently seen to be adopted in European countries relatively new to the use of HTA e.g. Estonia, Croatia 13

14. UK Benchmark for decisions: incremental cost per QALY gained (Historical) Source: Rawlins and Culyer, BMJ 2005;329:224-227 A = <£20,000 per QALY gained: -Considered an efficient use of resources B = >£30,000 per QALY gained -Would need special circumstances to accept Increasing cost/QALY (log scale) Probability of rejection on grounds of cost ineffectiveness

15. Questions of value in haemophilia Possible questions an HTA organisation could ask: Which approach to the treatment of haemophilia A with inhibitors offers the best value? Is the reimbursement of prophylactic use of factor VIII better value than treating bleeds on-demand in haemophilia A or B? Do new recombinant factor VIII products offer good value for money for use in prophylaxis compared to existing recombinant products such that they should be reimbursed? What additional benefits do they bring e.g. less frequent administration? 15

16. Published studies Most attention given to cost-effectiveness of prophylaxis versus on-demand factor VIII treatment (more recent attention on cost-effectiveness of inhibitors treatment) Early health economic studies (90’s) did not have QALY as the outcome measure Recent systematic review found 7 cost per QALY studies (CUA’s): Two were assessments of treatments for inhibitors Five were assessments prophylaxis v on-demand 16

17. Cost-utility analyses StudyStudy design and countries Utility measure used Ekert et al, 2001 CUA of recombinant factor VIIa (Novo7) v usual care for haemophilia with inhibitors Before and after NovoSeven. Single hospital - Australia Generic EQ 5D Knight et al, 2003 Alternative on-demand regimens for haemophilia A with inhibitors Decision model - UKGeneric EQ 5D Miners et al. 2002 & Miners 2009 Prophylaxis vs on-demand in severe haemophlia Markov model – UKGeneric EQ 5D Lippert et al, 2005 Prophylaxis vs on-demand in severe haemophlia Cross sectional study patients aged 14+ years – Ger, Swe, UK, Neth Generic SF 6D Risebrough et al 2008 Tailored prophylaxis, vs primary prophylaxis vs on-demand in young children 0-6 years Markov model - CanadaDirect Standard gamble in general public Colombo et al 2011 Prophylaxis vs on-demand in severe haemophlia Markov model - ItalyGeneric EQ 5D Farrugia et al 2013 Prophylaxis vs on-demand in severe haemophlia Markov model – US, UK, SweGeneric EQ 5D/SF 6D

18. Key results StudyTreatment/patients considered Incremental costs QALYs gained in a cohort Cost/QALY Result Miners 2009 Lifetime treatment with prophylaxis vs on- demand for severe haemophilia in UK (70 yrs follow-up) £214,0005.63£38,000 per QALY gained for primary prophylaxis Colombo, 2011 Lifetime treatment with prophylaxis vs on- demand for severe haemophilia in Italy (70yrs follow-up) €787,00016.03€40,000 per QALY gained for primary prophylaxis Ferrugia 2013 Lifetime treatment with prophylaxis vs on- demand for severe haemophilia in 4 countries -£280,000 (UK) SEK 5.3 million (Swe) 9.69 10.99 - SEK 485,000 per QALY gained 18

19. Importance of uncertainty! Cost-effectiveness prophylaxis vs on-demand is sensitive to: Perspective adopted Dosage and cost of factor VIII assumed Probability of inhibitor with prophylaxis vs on-demand Time horizon and discounting Quality of life estimated for prophylaxis vs. on-demand: 19 Source: Noone et al, 2013

20. HTA and payer questions of value of a new treatment What are the patient reported benefits – how many QALYs can be gained for the population? How high is the incremental cost per QALY gained – what is the opportunity cost of funding the new treatment? How robust, how uncertain are we of the costs and benefit – how much risk do we want to take? 20

21. Summary – HTA and payer perspective HTA is a supportive tool for decision making, based on demonstration of value. It takes a population rather than individual perspective, but what’s important in that perspective can vary. Can expect closer HTA scrutiny of haemophilia in the future: focussed on what value do new haemophilia treatments bring, are they worth paying a premium price? What value for longer half life, less frequent administration? Will payers be willing to pay more for this? 21