Vaccines related epidemiologyProgramme design

and policy options

First EpiTrain course in

Advanced Epidemiology Jurmala Latvia 29.10.2004

Hanna NohynekKTL Helsinki Finland

Vaccination Policy Options

Eradication Activities New Vaccine Introduction

Outbreak vs routine control of epidemic diseases

?

Newer Vaccine Research and Development

Evolution of Immunization Programmes

Pre-vaccine IncreasingCoverage

Loss of Confidence

1 2 3

Outbreak

AdverseEvents

Resumption of Confidence Eradication

4 5

Vaccinations Stops

Disease

Vaccine Coverage

Maturity of programme

Inci

den

ce

Ref: Grabenstein JD, Hospital Pharmacy 1996

When planning vaccinating (an individual or) a

population

Vaccine efficacy

Severity of disease

Risk to contractCoverage

Adverse events

Price

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 ?

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

Case Finland: Rationale and aims of

changes in programme 2001-Opportunity to make major revisions

arising from decision to stop national vaccineproduction (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 evaluationCarefully controlled implementation Follow up of implementation and evaluation of

effectiveness

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

Possible programmatic changes discussed

New combination vaccine to replace wP in DTwP

Reductions / omissionsBCG

Add ons hepatitis B, pertussis, influenza, pneumococcus (PPV),tick born encephalitis (regionally)

New vaccinesvaricella, pneumococcus (PCV), (meningococcus C)

Costs of the Finnish nEPIMilj. €

Vaccination programme in 2002 4,54

DTaP-Hib-IPV x 3 4,20Savings from stopping ownproduction and single doses -1,68

d/DTaP to >6-year olds 0,77

Influenza to >65-year olds 0,89

New (mandatory additions) 8,72

Population 5.2 mi, birth cohort 60 000

nEPI costs...

Milj. €

New (mandatory additions) 8,72

BCG-vaccine reductions -0,03

Stopping polio boosters -0,49

New (minimum) 8,20

Costs of new nEPI ?Milj. €

New (minimum) 8,20

Varicella x 2 3,93

Pnc-conjugate x 4 12,11Hepatitis B -vaccine x 3(part of a combo vacc) 1,51

New (maximum) 25,75

= 5 - fold difference !

Roles and responsibilities in decision making for nEPI

N ational Advisory C om m itteefor In fectious D iseases

National A dvisory C ommitteefor Vac c ination (K RAR)

Disease / Vaccine Specificw orking groups

KTL Advisory Boardon Vaccines

National Public Health Institute(KTL)

Minis try of Health

Disease / vaccine specific subgroup reports

• Pertussis• BCG• Varicella • Influenza• Pneumococcus (PPS, PCV) • Combination vaccines• Hepatitis B• TBE

VE evidence categorizedaccording to ~EBM

Cost effectiveness analyses

New decision making process adopted

= 4 steps approachFactors to consider

1) Expected public health benefit

2) Safety of vaccine individually

3) Safety effects on population level

4) Benefit / cost of vaccine

Outcome of the 4 step evaluation for 7PCV

1) Expected public health benefit

+

Efficacy of PncCRM vaccine

0 10 20 30 40 50 60 70 80 90 100

NCKP (all)

FinOM (all)

FinOM (PNC)

FinOM (VT)

Soweto (HIV+)

Soweto (HIV-)

Arizona (RSV-)

NCKP

Soweto

Arizona

NCKP

%

Acute Otitis

Pneumonia (X-ray positive)

Invasive Infections

3ISPPD 2002

Invasive Pnc infections in Finland in 1995-99

0

20

40

60

80

100

<5 5-9 10-14

15-19

20-24

25-29

30-34

35-39

40-44

45-49

50-54

55-59

60-64

65-69

70-74

>750

5

10

15

20

25

30

Age, years

Cases/year

Source: National Register for Infectious Diseases

Incidence/100 000/year7PCV serotypecoverage

67,5 %

49,4%

Incidence of pneumonia strongly affected by case definition

Also has an impact on expected VE of PCV

Incidence of Acute Otitis Media

02468

101214161820

2 3 5 7 9 11 13 15 17 19 21 23

Age, months

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

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 AOM2 400 otologic surgery procedures

4 steps approach for 7PCV

1) Expected public health benefit

+

2) Safety of vaccine+

large scale RC trials demonstrated safety

on individual level

4 steps approach for 7PCV

1) Expected public health benefit

+

2) Safety of vaccine+

3) Population level effects

+ herd effect

?/- replacement

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

Cost category

No

7PCV

Yes

7PCV

Net cost

€Total medical 26 486 016 22 303 132 - 4 182 884Vaccination programme 0 11 929 766 11 929 766

Health care 26 486 016 34 232 898 7 746 882

Travel 1 342 152 1 226 297 - 114 856

Total direct 27 827 169 35 459 195 + 632 026

Productivity 11 798 063 10 348 785 - 1 449 277

Total cost 32 625 232 45 807 980 +6 182 749

Costs € of introducing 7PCV into national program

Salo H et al. ESPID 2003

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

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.

 

Final conclusionExpert 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.

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.)

Further comment by WG

1. Introduction of new vaccines should not be compared to introduction of old vaccinesRight 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 !

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)

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

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

DTaP-Polio-Hib

National vaccination programme in 2005

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

Haemophilus influenza type b immunizationWHO European Region 2004

Source: Joint reporting form as of 30/09/2004

Euro52.shpUniversal infantPart of the countryNot introducedNo Data

Hib3 coverage in the WHO European Region 2003

>95

90-95

80-90

<80

No data

No immunization

0

5

10

15

20

25

30

35

40

45

50

Icel

and

Fin

land

Sw

eden UK

Sw

itzer

land

Den

mar

k

Isra

el

Net

herla

nds

Spa

in

Nor

way

Aus

tria

Slo

vaki

a

Fra

nce

Luxe

mbu

rg

Irel

and

Ital

y

Slo

veni

a

Cze

ch R

epub

lic

Mal

ta

Ger

man

y

Gre

ece

Pol

and

Bul

garia

Rus

sia

Fed

erat

ion

Cro

atia

Hun

gary

Latv

ia

maxmin

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

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?How accurate is this information?

Vaccine programmes for the rich vs. poor

5

6

7

8

9

10

11

12

13

1975 1985 1995 2004

RichPoor

• Rich: DTP, IPV, MMR + HBV, Hib + Varicella, PCV

+ Influenza• Poor:

BCG, DTP, OPV, M + HBV, (Hib)

• -> GAVI