1. Vaccines related epidemiology Programme design and policy options First EpiTrain course in Advanced Epidemiology Jurmala Latvia 29.10.2004 Hanna Nohynek KTL Helsinki Finland

2. Vaccination Policy Options Eradication Activities New Vaccine Introduction Outbreak vs routine control of epidemic diseases ? Newer Vaccine Research and Development

4. Evolution of Immunization Programmes Pre-vaccine Increasing Coverage Loss of Confidence 123 Outbreak Adverse Events Resumption of Confidence Eradication 45 Vaccinations Stops Disease Vaccine Coverage Maturity of programme Incidence Ref: Grabenstein JD, Hospital Pharmacy 1996

5. When planning vaccinating (an individual or) a population Vaccine efficacy Severity of disease Risk to contract Coverage Adverse events Price

6. Basic questions when introducing new vaccines into a national programme Is the vaccine efficacious enough and safe ? Is there big enough vaccine preventable disease burden in the country ? Is the public aware of the importance of the disease ? Is the vaccine coverage good ? How could the vaccine be introduced into the national schedule ? How can the country assure availability of the vaccine in long term ?

7. Decision making processes for introducing new vaccines vary greatly in industrialized countries Reasons -national health systems in place -funding basis of programme -gross national product -national prioritization health vs. other values within health

8. Case Finland: Rationale and aims of changes in programme 2001- Opportunity to make major revisions arising from decision to stop national vaccine production (to end by December 2004) Best possible/affordable protection to whole population National consensus process Revisions need to base on scientific evidence and cost effectiveness evaluation Carefully controlled implementation Follow up of implementation and evaluation of effectiveness

9. Age <1 weeks 3 mo 4 mo 5 mo 6 mo 12 mo 14-18 mo 20-24 mo Vaccine BCG DTwP DTwP + Hib DTwP Polio + Hib Polio MMR + Hib DTwP + polio Injections National vaccination programme in 2001

10. Possible programmatic changes discussed New combination vaccine to replace wP in DTwP Reductions / omissions BCG Add ons hepatitis B, pertussis, influenza, pneumococcus (PPV), tick born encephalitis (regionally) New vaccines varicella, pneumococcus (PCV), (meningococcus C)

11. Costs of the Finnish nEPI Population 5.2 mi, birth cohort 60 000

12. nEPI costs...

13. Costs of new nEPI ? = 5 - fold difference !

14. Roles and responsibilities in decision making for nEPI

15. Disease / vaccine specific subgroup reports Pertussis BCG Varicella Influenza Pneumococcus (PPS, PCV) Combination vaccines Hepatitis B TBE VE evidence categorized according to ~EBM Cost effectiveness analyses

16. New decision making process adopted = 4 steps approach Factors to consider 1) Expected public health benefit 2) Safety of vaccine individually 3) Safety effects on population level 4) Benefit / cost of vaccine

17. Outcome of the 4 step evaluation for 7PCV 1) Expected public health benefit +

18. Efficacy of PncCRM vaccine Acute Otitis Pneumonia (X-ray positive) Invasive Infections 3ISPPD 2002

19. Invasive Pnc infections in Finland in 1995-99 Age, years Cases/year Source: National Register for Infectious Diseases Incidence/100 000/year 7PCV serotype coverage 67,5 % 49,4%

20. Incidence of pneumonia strongly affected by case definition Also has an impact on expected VE of PCV

21. Incidence of Acute Otitis Media AOM / 100 childmonth FinOM cohort Pilot study All AOM AOM by Pnc AOM is most common among children 7-12 mo of age. Kilpi et al. Pediatr Infect Dis J 2001;20:654-62

22. Pnc disease burden in Finland Birth cohort 60 000 Universal use of 7PCV potentially prevents annually 50 - 60 cases of IPD 500 - 1 800 cases of pneumonia 10 000 episodes of AOM 2 400 otologic surgery procedures

23. 4 steps approach for 7PCV 1) Expected public health benefit + 2) Safety of vaccine + large scale RC trials demonstrated safety on individual level

24. 4 steps approach for 7PCV 1) Expected public health benefit + 2) Safety of vaccine + 3) Population level effects + herd effect ?/- replacement

25. 4 steps approach for 7PCV 1) Expected public health benefit + 2) Safety of vaccine + 3) Population level effects + herd effect, ? replacement 4) Benefit / cost of vaccine - with 4 doses

26. Cost category No 7PCV Yes 7PCV Net cost Total medical 26 486 01622 303 132- 4 182 884 Vaccination programme 011 929 766 Health care 26 486 01634 232 8987 746 882 Travel 1 342 1521 226 297- 114 856 Total direct27 827 16935 459 195+ 632 026 Productivity11 798 06310 348 785- 1 449 277 Total cost32 625 23245 807 980+6 182 749 Costs of introducing 7PCV into national program Salo H et al. ESPID 2003

27. Cost effectiveness of 7PCV in Finland 1) The price of 7PCV should be third (half) the price 2) Effect of reducing number of 7PCV doses and/or using 23PncPS for boosting needs to be evaluated 3) Benefits = quality of life > life years saved Salo H et al. ESPID 2003

28. Conclusion from step 4 evaluation Introduction of 4 doses of 7PCV would almost triple the costs of universal childhood vaccination program compared to the 2001 level, even if all savings achieved by reduced disease burden were taken into account.

29. Final conclusion Expert consensus: even if pneumococcus causes substantial public health disease burden, 7PCV is safe and possibly has positive herd effect extending to older age groups, 7PCV is not cost efficacious if given according to the recommended 4-dose schedule; therefore, at the time being 7PCV is not recommended to be implemented into national vaccination program in Finland.

30. Further comment by WG Introduction of new vaccines should not be compared to introduction of old vaccines Right comparision = new vaccines vs. any other preventive health intervention (screening for prostate cancer, hip replacement, etc.)

31. Further comment by WG 1. Introduction of new vaccines should not be compared to introduction of old vaccines Right comparision = new vaccines vs. any other preventive health intervention (screening for prostate cancer, hip replacement, etc.) 2. Any health intervention to be introduced should have a firm scientific evidence base 3. Limited resources should be targeted at interventions with equal benefit obtained with least amount of costs Shift of paradigm !

32. In October 2004, Finland is -Getting ready to introduce a new routine infant immunization programme without 7PCV (January 2005->) -Recalculating costs and benefits taking into consideration accumulating evidence of the effects of 7PCV (herd immunity, need of less than 4 doses, replacement)

33. Age <1 weeks 3 mo 4 mo 5 mo 6 mo 12 mo 14-18 mo 20-24 mo Vaccine BCG DTwP DTwP + Hib DTwP Polio + Hib Polio MMR + Hib DTwP + polio Injections National vaccination programme in 2004

34. Age <1 weeks 3 mo 4 mo 5 mo 6 mo 12 mo 14-18 mo 20-24 mo Vaccine BCG DTaP-Polio-Hib MMR Injections DTaP-Polio-Hib National vaccination programme in 2005

35. 11 countries receiving support from GAVI/VF Universal newborn Universal infant Universal adolescent No universal Hep B Immunization Hep B immunization policy WHO European Region, 2004

36. Haemophilus influenza type b immunization WHO European Region 2004 Source: Joint reporting form as of 30/09/2004

37. Hib3 coverage in the WHO European Region 2003 >95 90-95 80-90 <80 No data No immunization

38. Annual incidence of Hib meningitis in children <5 years of age before the introduction of immunization based on about 70 studies in countries of the WHO European Region

39. Other new and under-used antigens in the European Region (as shown on the WHO/UNICEF Joint Reporting Forms for 2003) Accellular pertussis vaccine (aP and aP- containing vaccines) –25 countries (WE and CCEE) Meningococcal conjugate vaccine –10 WE countries Pneumococcal conjugate vaccine –6 WE countries Varicella vaccine –2 WE countries How accurate is this information?

40. Vaccine programmes for the rich vs. poor Rich: DTP, IPV, MMR + HBV, Hib + Varicella, PCV + Influenza Poor: BCG, DTP, OPV, M + HBV, (Hib) -> GAVI