1. The journey to sustainable and widespread improvement – medicines matter Prof Dyfrig Hughes PhD MRPharmS Centre for Health Economics and Medicines Evaluation Bangor University

2. Overview 1. Economics of medicines  New medicines  Wasted medicines 2. Patients’ perspective  Preferences  Adherence

3. Demand Lancet DOI:10.1016/S0140-6736(12)60240-2

4. Supply (Wales corrected to -8.3%) (Scotland corrected to -1.3%) BMJ 2011;342 doi: 0.1136/bmj.d2982

5. Cost-effectiveness threshold Rawlins and Culyer, BMJ 2004;329:224-227 A = <£20,000 per QALY gained B = >£30,000 per QALY gained Increasing cost/QALY (log scale) Probability of rejection on grounds of cost infectiveness

6. “An assumption that underlies most of NICE's technology appraisals has been that “a QALY is a QALY is a QALY.” By this NICE means that a QALY gained or lost in respect of one disease is equivalent to a QALY gained or lost in respect of another. It also means that the weight given to the gain of a QALY is the same, regardless of how many QALYs have already been enjoyed, how many are in prospect, the age or sex of the beneficiaries, their deservedness, and the extent to which the recipients are deprived in other respects than health.” QALY is a QALY is a QALY Rawlins & Culyer. BMJ 2004;329:224

7. “I am uneasy about the mantra of ‘a QALY is a QALY is a QALY.’ It means that an increase in utility from 0.3 to 0.5 is valued the same as an increase from 0.7 to 0.9. I am not sure this is fair.” Rawlins. Value in Health 2012;15:568-9 QALY is a QALY is a QALY ^ not ^

8. Departing from the threshold For each £1m spent on a medicine whose ICER is twice the threshold (e.g. £50k/QALY):  Gain 20 QALYs  Lose 40 QALYs Net population loss of 20 QALYs

9. Departing from the threshold End-of-life criteria  Weightings applied to quality of life experienced at the end of life for life- extending medicines Cancer Drugs Fund Ultra-orphan drugs  Additional allowances in recognition of ICERs exceeding the threshold Value-Based Pricing criteria

10. Value-Based Pricing: Aims to Improve outcomes for patients through better access to effective medicines; Stimulate innovation and the development of high value treatments; Improve the process for assessing new medicines, ensuring transparent predictable and timely decision- making; Include a wide assessment, alongside clinical effectiveness, of the range of factors through which medicines deliver benefits for patients and society; Ensure value for money and best use of NHS resources.

11. Value-Based Pricing: Criteria Society may place a greater weight on treating particularly severe or life threatening conditions - SEVERITY The current system [of appraisal] may not fully reflect society’s preferences if there are no existing alternative treatments and so a significant unmet need – UNMET NEED A treatment representing a significant breakthrough … could also be represented by a qualitative assessment of the innovation reported by a new medicine reflecting, for example, new modes of action - INNOVATION Impacts of a product beyond direct health effects e.g. benefits related to reduced reliance on carers and other wider societal factors – NON-HEALTH-RELATED BENEFITS

12. Aligned with public preferences? Cross sectional survey (n=4,118) Asked respondents to choose between competing hypothetical patient groups

13. CriterionComparisonRationale ChildrenChildren vs. adultsNICE Disease rarityCommon disease vs. rare diseaseACNSS; AWMSG; SMC Disease severitySevere disease vs. moderate diseaseNICE; VBP Unmet needSeveral other treatment options available vs. none VBP CancerCancer vs. non-cancer diseaseCDF End of Life treatment Short life expectancy (18mths) vs. Longer life expectancy (60mths) NICE; AWMSG Disadvantaged populations Disadvantaged patient populations vs. Non- disadvantaged populations NICE InnovativeMedicine works in similar way to others vs. Medicine works in a new way NICE; VBP Wider societal benefits Patients reliant on carers vs. patients not reliant on carers VBP

14. Results Funding preferences exists for:  Severe disease  Medicines that address unmet needs  Medicines having wider societal benefits  Medicines that work in new way, but only when coupled with considerable improvement in health No funding preference for other criteria

15. Policy implications Value-based pricing  All 4 proposed criteria for rewarding new medicines with higher prices are supported Cancer Drugs Fund  Not supported Medicines for rare diseases  Policies that prioritise funding for rare diseases are not supported End-of-life treatments  No support for preferential funding allocation

16. Patients’ perspectives Patients have views too! Most patients are non-adherent most of the time Intentional non-adherence  can be thought as a revealed preference for a medicine Unintentional non-adherence  E.g. forgetting, cost barrier

17. Am J Med 2012; 125: 882-887 % Adherence to cardiovascular medicines

18. Breast Cancer Res Treat. 2010 Aug;122(3):843-51 Tamoxifen: Data from The Netherlands

19. J Clin Oncol. 2011 May 1;29(13):1657-63 RCT of 2 vs. 5 yrs tamoxifen

20. ABC project EU-funded “Ascertaining Barriers for Compliance” n=2,595 patients Prevalence  Antihypertensives Determinants  Multiple patient-, therapy-, condition-, social- and healthcare-system-related factors determine adherence

21. Netherlands (237) [24%] Germany (274) [33%] Austria (323) [34%] Wales (323) [38%] Belgium (180) [39%] England (323) [41%] Greece (289) [50%] Poland (323) [58%] Hungary (323) [70%] Total (2595) [44%] ■ ■ Overall non-adherence □ □ Intentional non-adherence 0% Non adherence

22. Odds Ratio[95% CI] Age0.98***0.970.99 Employment0.74*0.580.95 Number of medicines0.90***0.860.94 Dosage frequency1.28**1.091.50 Self-efficacy0.73***0.690.77 Barriers (TPB)1.10*1.011.19 Satisfaction with practitioner1.01*1.001.02 Barriers1.25**1.061.47 Personal control0.93**0.890.97 Concern about illness0.96*0.930.99 Borrowing money0.82***0.750.90 Constant34.25***12.2995.46 Main survey results

23. Stated preference

25. Am J Med 2012;125(9):888-96 Pay patients to adhere?

26. Conclusions Cost of new medicines set to increase  serious questions need to be asked about the value of new medicines  Many current criteria for prioritising treatments do not reflect societal preferences Reassuring that VBP criteria seem to be supported

27. Conclusions Patients don’t take their medicines  Clinical consequences  Economic consequences Methods for improving adherence needed  Must first understand the underlying reasons

29. He was prone to memory lapses when not taking medication for mental health problems