Cost-effectiveness of paediatric seasonal influenza vaccination in England and Wales

1. Cost-effectiveness of paediatric seasonal influenza vaccination in England and Wales RJ PitmanICON Health Economics, Oxford, UKCanadian Public Health Association Conference Toronto, CanadaMay, 2014

2. Why conduct cost-effectiveness analyses? • Health policy is formulated to maximise the health of the population • Budgets are finite • So how do we most efficiently use these limited resources?

3. Costs Policy A Outcomes  Benefit  Cost Choice :Policy A or B ? Outcomes Policy B Costs Incremental costs and benefits Does the extrabenefit justify the extra cost ?

4. Cost-effectiveness plane New treatment more costly New treatment more costly and more effective Old treatment dominates New treatment less effective New treatment more effective New treatment less costly and less effective New treatment dominates New treatment less costly

5. Cost-effectiveness and opportunity cost Cost Cost-effectiveness threshold £20,000 per QALY Price > P* £60,000 £30,000 per QALY Price = P* £40,000 £20,000 per QALY Price < P* £20,000 £10,000 per QALY QALYs gained 1 2 3 Net Health Benefit 1 QALY Net Health Benefit -1 QALY

6. The region of cost-effectiveness Difference in cost Cost-effectiveness threshold Difference in effect Region of cost-effectiveness

7. Cost-effectiveness plane l = cost-effectiveness threshold l

8. Cost effectiveness acceptability curve New Treatment 100% 80% Probability most cost-effective 50% 20% Current Treatment Cost-effectiveness threshold (l)

9. Moving from the ICER to net benefit Threshold defines value of health outcome Standard ICER decision rule: ΔC/ΔQ < λ Where λ is the threshold Net monetary benefit: (ΔQ x λ) – ΔC > 0 Net health benefit: ΔQ – (ΔC/ λ) > 0

11. Influenza vaccination In England and Wales vaccination against seasonal influenza was only offered if: • Over six months old and at an increased risk of influenza complications • This included everyone over the age of 65 years and anyone younger who falls into a predefined risk group

12. Influenza vaccination • Base case Influenza vaccination (status quo) • 6mo - <65yrs at risk of influenza related complications • 65+yrs vs Paediatric influenza vaccination • Status quo + 2yrs - <19yrs

13. The components of a vaccine cost-effectiveness model Pitman et al. Vaccine (2012) 30: 1208-1224

14. Who Acquires Infection From Whom (WAIFW) matrix Mossong J et al.PLoS Med (2008) 5: 381-391

15. The components of a communicable disease model Vynnycky E et al. Vaccine (2008) 26: 5321-5330

16. B(Vic) B(Yam) AH3N2 AH1N1 Pitman et al. J Infect (2007) 54: 530-538

17. Incremental cost effectiveness analysis over 15 years, at 50% uptake

18. 15 year cumulative burden of influenza, at 50% uptake CP + 2-18 yrs CP + 2-4 yrs Current practice (CP) No vaccination Pitman et al. Vaccine (2013) 31: 927-942

19. Cost effectiveness acceptability curves, using 15 year cumulative data, at 50% No vaccination Current policy CP + 2-18 yrs CP + 2-4 yrs Pitman et al. Vaccine (2013) 31: 927-942

20. Conclusions • Paediatric vaccination is likely to result in substantial health savings both within and beyond the vaccinated cohorts of children • While there is considerable uncertainty in the system, annual paediatric influenza vaccination was consistently estimated to be cost-effective

21. Thank You Contributors: Lisa Nagy – ICON Health Economics Mark Sculpher – York Centre for Health Economics Richard.Pitman@ICONplc.com

22. Reserve slides

23. Decisions when a treatment does not dominate • Assessing the opportunity cost • What existing treatments will have to be displaced? • What health benefits will be forgone? • A rule of thumb • How does the extra cost of a unit of benefit comparewith previous decisions? • What is society willing to pay for an extra unit of benefit? • Increase insurance premiums/taxation to provide new intervention

24. Influenza virus • Constantly changing virus • Comes in two types: A and B • Influenza A • Responsible for pandemics • Has numerous subtypes • A(H1N1) – 1918 • A(H2N2) – 1957 • A(H3N2) – 1968 • A(H1N1/09) – 2009 PHIL ID #11823, Dan Higgins, CDC

25. Burden of influenza in England & Wales The annual health burden of seasonal influenza is considerable Very roughly: • 1 million General Practice consultations • 25,000 Hospitalisations • 20,000 Deaths Pitman R et al, J Infect, 2007, 54, 530-538

26. Estimated annual rate of influenza A relatedprimary care consultations Pitman R et al, J Infect, 2007, 54, 530-538

27. Estimated annual rate of influenza A relatedhospitalisations Pitman R et al, J Infect, 2007, 54, 530-538

28. Estimated annual rate of influenza A relateddeaths Pitman R et al, J Infect, 2007, 54, 530-538

29. The debate: Who should we be targeting? • Those at greatest risk of complications? • Or a combination of both? • Those most likely to transmit the virus? Influenza virion TEM: #10073 CDC/ Dr. Erskine. L. Palmer; Dr. M. L. Martin

30. Objective • To assess the cost effectiveness of adopting a policy of routine childhood influenza vaccination in the England and Wales, taking account of the dynamics of transmission and indirect protection (herd protection)

31. Herd Immunity Susceptible Immune following infection Vaccinated Protected by herd immunity

32. Current policy High risk groups • 65+ years old • 6 months – 64 years old in the following groups: • Residents of nursing or residential homes for the elderly and other long-stay facilities • or with the following conditions: • Chronic respiratory disease (includes asthma treated with continuous or repeated use of inhaled or systemic corticosteroids or asthma with previous exacerbations requiring hospital admission) • Chronic heart, liver or renal disease • Chronic neurological disease • Diabetes mellitus • Immunosuppression because of disease or treatment • HIV infection (regardless of immune status) • Carers of the above • Health care workers • Pregnant women

33. Methods: Univariate sensitivity analysis • Population mixing • Homogeneous (random) • Basic reproductive rate • 1.4 • 2.2 • No Seasonality • Seeding • 10 / year / age band; 5 – 50 years of age • Vaccine Coverage • 10% • 50% • 80%

34. Status quo • Elderly (65+yrs) and at risk groups vaccinated • Annually from 2000 onwards • Jefferson T. et al Cochrane Database Syst Rev, CD004879 2008 • Jefferson T. et al Cochrane Database Syst Rev, CD001269 2007 • Rivetti, D. et al Cochrane Database Syst Rev, CD004876 2006 • 2. Health Protection Agency data

35. Paediatric vaccination • Annually from 2009 onwards • Efficacy 80% 1,2 • Coverage 50% • Target age groups • Pre-school: 2 - <5 • Primary School age: 5 - <11 • Secondary school age: 11-<19 • Jefferson T. et al Cochrane Database Syst Rev, CD004879 2008 • Jefferson T. et al Cochrane Database Syst Rev, CD001269 2007 • Rivetti, D. et al Cochrane Database Syst Rev, CD004876 2006 • Belshe, R. B. et al N Engl J Med, 2007, 356, 685-696 • Rhorer, J. et al Vaccine, 2009, 27, 1101-1110

36. Cost-effectiveness analysis

37. Assumptions • Health Service (NHS) perspective • 3.5% discount rate applied to both costs and benefits

38. Costs • Vaccination • GP consultation • Vaccine price point • TIV – mean list price • LAIV = TIV • Health outcomes – age stratified mean cost of influenza related • GP consultation • Hospitalisation • Costs inflated to 2009 prices, where appropriate

39. Outcomes • Averted • General practice consultations • Hospitalisations • Deaths • Quality adjusted life years • QALY decrements based on estimates from 2003 HTA report1 • Adult QALYs used • Turner D et al Health Technol Assess. 2003; 7: 1-170

40. Sensitivity analyses • Univariate sensitivity analysis • Probabilistic Sensitivity analysis • Variation in probabilities: beta distribution • Variation in costs and utility decrements: gamma distribution • Probability cost-effective: Cost-effectiveness acceptability curve (CEAC) • Probability of option with highest net benefit being cost-effective: Cost-effectiveness acceptability frontier (CEAF) • Extreme value analysis

41. Extreme Value Analysis • The transmission coefficient (R0 of 1.4, 1.8 and 2.2) • Infectious cases seeded into the population each year (50, 100, 150) • Duration of natural immunity (influenza A: 5 years, 6 years, 7 years; influenza B: 11 years, 12 years, 13 years) • Duration of infectiousness (1 day, 2 days, 5 days) • Percentage of infected individuals that experience symptoms (55%, 64%, 73%) • Latent period (1 day, 2 days, 3 days) • Duration of vaccine induced immunity (Flu A: 3 years, 6 years, 7 years; Flu B: 6 years, 12 years, 13 years)

42. Vaccination of elderly Paediatric vaccination Simulated influenza

43. Results: Sensitivity of the 15 year cumulative averted influenza cases per 100,000 population, assuming 80% coverage of 2 to 18 year old children with LAIV in addition to current practice

44. Extreme value analysis Influenza A Influenza B

45. The cost of an influenza related GP consultation General Practice Research Database 2000 - 2009 Personal and Social Services Research Group Report 2008

46. The cost of an influenza related hospitalisation Hospital Episode Statistics 2005-06 NHS National Schedule of Reference Costs 2007-08

47. Annual primary care and hospitalisation costs of influenza in England & Wales Total annual cost ~ £175,000,000 Hospital Episode Statistics 2005-06 NHS National Schedule of Reference Costs 2007-08 General Practice Research Database Person and Social Services Research Unit annual report Pitman R et al, J Infect, 2007, 54, 530-538

48. Results: Sensitivity of ICER to time horizon, at 50% uptake

49. 15 year estimated cumulative burden of influenza, at increasing levels of paediatric vaccine uptake

50. Cost effectiveness acceptability frontier, based on 15 year cumulative data, at 50% uptake