How to Define Influenza?

Seasonal Influenza
Vaccination in Europe
Thomas D. Szucs, MD
Patricia R. Blank, PhD
Institute of Pharmaceutical Medicine
European Center of Pharmaceutical Medicine
University of Basel
Switzerland
Overview
• On efficacy and
effectiveness
• On policy
• On economics
3
3
Efficacy* / Effectiveness** of
Influenza Vaccination
in different population segments
* Efficacy = randomized, controlled trials
** Effectiveness = observational trials
How to Define Influenza? No gold standard clinical
case definition for influenza
URI
Influenza
Illness
Influenza
infection
Lab
confirmed
influenza ILI
Hosp /
Death
Implications of the heterogeneity of influenza case definitions: care
must be exercised in interpreting and comparing the results of studies
assessing vaccine efficacy and effectiveness
K.L. Nichol / Vaccine 24 (2006) 6726–6728
How to Define Influenza?
No gold standard clinical case definition for influenza
Lab
confirmed
influenza
89%
100
Vaccine
effectiveness
90
ILI
80
70
60
50
63%
Acute
respiratory
illness
60%
40
30
28%
20
10
0
Specificity
Influenza Vaccine in CommunityDwelling Elderly
Cohort studies
RCTs
Outcome
Risk Ratio
95% CI
Flu-like illness
0.59
(0.47, 0.73)
Influenza
0.42
(0.27, 0.66)
Influenza
admissions
0.52
(0.30, 0.90)
Deaths (all cause)
1.02
(0.11, 9.72)
Flu-like illness
1.05
(0.58, 1.89)
Influenza
0.19
(0.02, 2.01)
Resp admissions
0.88
(0.54, 1.43)
Influenza
admissions
0.72
(0.62,0.85)
Deaths (influenza)
0.87
(0.70, 1.09)
Deaths (all cause)
0.58
(0.45, 0.67)
The choice of the outcome can
dramatically affect the numbers reported
Jefferson T, Cochrane Review
Randomized Placebo-controlled
Trials Among Young Adults
Efficacy of Inactivated Vaccine Against
Lab-confirmed* Influenza, Michigan
Season
Placebo (%+)
Trivalent
Inactivated
Vaccine (%+)
2004-20051
7.8
1.9
75% (42 to 90)
2005-20062
1.8
1.5
16% (-171 to 70)
2007-20083
10.8
3.4
68% (46 to 81)
Vaccine Efficacy
(95% CI)
1. Ohmit SE, et al. N Engl J Med. 2006;355:2513-2522. 2. Ohmit SE, et al. J Clin Infect Dis. 2008;198:312-317.
3. Monto AS, et al. N Engl J Med. 2009;361:1260-1267. Fiore, CDC, Atlanta
*Culture and/or polymerase chain reaction (PCR) assay. CI = confidence interval.
TIV Effectiveness Estimates by Age
and Risk Group
When Vaccine Strains Match Circulating Strains,
Using a Variety of Study Designs
Age/Risk Group
Outcome
Effectiveness*
6 months-18 years
Influenza†
50-90%
18-64 years
Influenza†
50-90%
>65 years, community
Influenza†
50-70%
Influenza†
30-40%
Hospitalization or death
40-80%
Elderly, nursing home
Pregnant women
Influenza in newborn†
ILI in mother
63%
36%
* Effectiveness is lower when vaccine and circulating strains are
antigenically different. No vaccine effectiveness is sometimes observed
when the prevalence of antigenically different strains is high.
CDC. MMWR Morb Mortal Wkly Rep. July 12, 2009;58:1-52.
†Laboratory-confirmed influenza virus infection.
Fiore, CDC, Atlanta
Recommendations on influenza vaccination
are getting stronger worldwide
WHO guidelines
European Union
recommendations
2010 ACIP
recommendations
Target:
Target:
Universal vaccination
75% coverage
for the adults over 65
by 2010/2011 1
75% coverage
for the adults over 65
by 2014/2015 2
for people aged
6 months and older 3
Overall, more than 50 countries fund influenza vaccination
to nationally defined high-risk groups 1
1) World Health Organization. Wkly Epidemiol Rec 2005; 33: 277–288. 2) EPHA. Council recommendation of 22 December 2009 on
seasonal influenza vaccination. 3) ACIP. Prevention and Control of Influenza with Vaccines Recommendations of the Advisory
Committee on Immunization Practices (ACIP), 2010. MMWR, August 6, 2010; 59(rr08):1-62
Global coverage
Russia
Estonia
Latvia
Lithuania
Poland
Denmark
United Kingdom
Czech Republic
Bulgaria
Serbia
Spain
Portugal
Turkey
Morocco
Tunisia
Algeria
Venezuela
Mexico
South Korea
China
Saudi
Arabia
Brazil
South Africa
Chile
Uruguay
Argentina
Sanofi Pasteur internal data (2010)
Malaysia
Singapore
40-60%
20-40%
10-20%
5-10%
<5%
Not available
Thailand
Influenza vaccination of adults over 65:
Recommendation & Reimbursement by country
Russia
Estonia
Latvia
Lithuania
Poland
Denmark
United Kingdom
Czech Republic
Bulgaria
Serbia
Spain
Portugal
Turkey
Morocco
Tunisia
Algeria
Venezuela
Mexico
South Korea
China
Saudi
Arabia
Brazil
Malaysia
Singapore
South Africa
Chile
Uruguay
Argentina
Recommendation & Funding
Recommendation & No funding
No recommendation
Not available
Adapted from Vaxiworld/ Omnibus surveys (2006) and Sanofi Pasteur internal data (2010)
Thailand
Vaccine coverage rates vary considerably
across Europe
Blank et al. J Infect. 2009 Jun;58(6):446-58.
17
Policies on seasonal influenza
vaccination coverage rates
Official vaccination recommendations
across EU countries
GBR NLD
FRA
ESP
ITA
50+
60+
IRL
BEL
DEU CHE
FIN
SWE PRT
CZE
SVK
*
Some
Regio
ns
No Yes
POL BGR
55+
*
65+
Chronic Disease
Sufferers incl.
children
School-age
children (all)
3M12Y
Children < 3 y.o.
(all)
3M12Y
Healthcare
professionals
Pregnant women
*Recommendation/ reimbursement with lower priority than 65+
Blank and Szucs, unpublished data, 2010
19
Implemented policy elements among
European countries differ considerably
GBR
NLD
FRA
Recommendation for <65 years
ESP
ITA
IRL
a)
BEL
DEU
CHE
FIN
SWE
PRT
CZE
SVK
POL
BRG
b)
National object per year for flu
Monitoring VCR each year by target (By HA
and/or NVIG)
HCW have objective to achieve in high risk
groups (GP and/or Specialist)
a)
d)
HCW financial incentive (yes/no)
d)
c)
a)
e)
Reimbursement of vaccine (90-100%)
Letter for free flu vaccine (from HA/ GP/ HC)
a)
Awareness campaigns: Radio and tv
d)
d)
a)
*
a)
d)
a)
f)
Awareness campaigns: press adverts
a)
a)
Awareness campaigns: Flyers in medical waiting
rooms
Awareness campaigns: Website for public
Awareness campaigns: Press / media
conference for pub
a)
d)
d)
No Yes
VCR, vaccination coverage rates; HA, Health Authority; NVIG, National Vaccine Industry Group; GP, general practitioners; HC, Health centre
a)regionally restricted; b) reimbursement with lower priority than 65+; c) some information available; d) not uniformly implemented; e) GP consult
fee or nurse fee; f) Past years
* Since 2009: in the face of a pandemic, the Ministry of Health has issued an act saying about a special program of vaccination for HCW
20
Blank and Szucs, unpublished data, 2010
Which factors can predict influenza
vaccinations?
France
Germany Italy
United
Spain
Kingdom
Austria
Czech
Republic
Finland
Ireland
Poland
Portugal
Belonging to risk group*
Gender (Male)
Size of household:
2 vs 1 person/s
≥ 3 vs 1 person/s
Size of town:
2nd smallest vs smallest category
2nd largest vs smallest category
Largest vs smallest category
Level of education:
Secondary vs primary
Tertiary vs primary
Household income :
Middle to lowest category
Highest to lowest category
* Includes persons aged ≥ 65 years, or suffering of chronic illness, or working in medical field
Positive predictor;
Negative predictor;
Factor with no significant odds ratio;
21
Not applicable
Endrich MM et al, Vaccine. 2009 Jun 19;27(30):4018-24.
Influenza
Diagnostic tool
Influenza Diagnostic tool
• There is a need for:
Understanding the impact of vaccination policies
Determining ways to improve seasonal influenza VCRs among
recommended groups
• The main aim of this study was:
To identify essential elements of vaccination policies
To identify the influence of policy-related driving factors on
vaccine uptake rates among the elderly
23
Methods
• Survey with 15 European national vaccine industry
groups regarding vaccination policies in each country
related to 4 main areas (2009)
1. Management of vaccination programmes
2. Influence of health care workers (HCWs)
3. Price and practical access to vaccine
4. Role of information & communication campaigns to the general
public
• The information retrieved was put in relation to current
national vaccination rates among the adults over 65 years
of age
• Correlation coefficients
24
There is a variety of immunization policies available –
but do countries take advantage of them?
GBR
NLD
FRA
Recommendation for <65 years
1.
2.
d)
HCW financial incentive (yes/no)
d)
e)
BEL
DEU
CHE
FIN
SWE
Letter for free flu vaccine (from HA/ GP/ HC)
Awareness campaigns: press adverts
CZE
SVK
POL
BRG
c)
a)
*
a)
a)
f)
PRT
VCRs affected by
number of
implemented policy
items?
a)
Awareness campaigns: Radio and tv
4.
IRL
b)
a)
Reimbursement of vaccine (90-100%)
3.
ITA
a)
National object per year for flu
Monitoring VCR each year by target (By HA
and/or NVIG)
HCW have objective to achieve in high risk
groups (GP and/or Specialist)
ESP
a)
d)
d)
d)
a)
a)
Awareness campaigns: Flyers in medical waiting
rooms
Awareness campaigns: Website for public
Awareness campaigns: Press / media
conference for pub
a)
d)
d)
No Yes
VCR, vaccination coverage rates; HA, Health Authority; NVIG, National Vaccine Industry Group; GP, general practitioners; HC, Health centre
a)regionally restricted; b) reimbursement with lower priority than 65+; c) some information available; d) not uniformly implemented; e) GP consult fee or nurse fee; f) Past years
* Since 2009: in the face of a pandemic, the Ministry of Health has issued an act saying about a special program of vaccination for HCW
Policy elements can have an impact on
VCRs as stand-alone or combined element
HCW financial incentives
(payment fee or additional
revenue)
HCW objectives for
their risk groups
Awareness
campaign: Radio-TV
Awareness
campaign: flyers in
medical rooms,
press adverts,
website
National policies
impacting
influenza
coverage rate
Reimbursement of flu
vaccine (90-100%)
National objectives per
year (VCR)
Personal letter for
free flu vaccine or
voucher
Monitoring VCR
Positive correlation of stand alone policy
Positive correlation if 2 policies are
combined
26
Positive correlation of stand-alone policy, Spearman's rho ρ (p-value < 0.05)
A combination of three elements showed strongest
associations with VCR among the elderly
National
objectives
Spearman's
ρ)
rho (ρ
National
objectives
&
HCW financial
incentive
&
Reimbursement
of vaccine (100%)
Patients
receive
personal
letter/voucher
for free flu
vaccine
&
Reimbursement
of vaccine (100%)
Monitoring
VCR
(By HA and/or
NVIG)
Monitoring VCR
(By HA and/or NVIG)
•
•
•
0.734
Letter or
free flu
vaccine
Radio
and tv
(yes/no)
100%
reimburse
ment of
vaccine
Flyers in
medical
waiting
rooms
0.607
0.631
0.607
0.694
0.558
HCW
financial
incentive
0.734
0.721
Flyers in medical waiting rooms
Personal invitation letters for free flu vaccine
Reimbursement of vaccination
Positive correlation of three policies, ρ (p-value < 0.05)
NB: Correlation coefficients to indicate probable directions of effects. Statistically significant correlations were not expected to be seen
VCR, vaccination coverage rates; HA, Health Authority; HCW, Health care worker;
NVIG, National Vaccine Industry Group.
0.820
What are the implications of this tool?
1.Its not the quantity, but the quality
which counts
2.There are policies with a higher
or lower impact on VCR
3.Cultural and religious beliefs and
socioeconomic factors might have
an additional influence
4.BUT, initiatives on political,
governmental, scientific and
community level are urgently
needed to meet the goal of 75%
28
Policy elements
≥ 10
8-9
6-7
4-5
≤3
What are the limitations?
• Limited number of countries included
• Restricted level of detail of the survey data
• Duration and timing of the awareness
campaigns were not taken into account
31
Influenza
Economic Considerations
Cost-effectiveness of flu vaccination in
Poland
• Health outcomes and
costs associated
• Third-party payer
Diagram of the model structure and key
parameters from the moment when
individuals are infected by influenza.
perspective
Cases
Influenza
vaccination
Healthy
New situation
• Influenza vaccination in
No vaccination
elderly compared to a
current situation
–
Vaccination paid by the
private sector
• out-of-pocket
• other private insurance funds
Karina Jahnz-Rozyk et al., unpublished data
HR
Influenza
vaccination
Population
65+
Existing situation
LR
No vaccination
Considerable consequences due public
funding of influenza vaccination
• Introduction of the public funding of influenza
vaccination for 65+ in Poland (reimbursement level: 100%)
– Assumed vaccination rate: 40% (currently 13.5%)
– Cost of vaccination program: PLN 79 million
– Effects per year:
• 23,900 cases of influenza averted
• 1,777 hospitalisations averted
• 548 premature deaths averted
Karina Jahnz-Rozyk et al., unpublished data
42
42
Health economic consequences of flu
vaccination
• If Influenza vaccination fully funded for 65+
– Incremental cost-effectiveness ratio: 26,118 PLN / QALY
(compared to no reimbursement)
– Third party perspective
– Below the yearly annual GDP per capita in Poland (PLN
34,015 in 2009)
• The number of people needed to be vaccinated to
prevent
– One case of influenza: 57 individuals
– One hospitalisation: 842 individuals
– One death: 2,809 individuals
Karina Jahnz-Rozyk et al., unpublished data
43
Increase of vaccine use in the European Union (EU)
would result in an important reduction of influenza
burden
• Increasing vaccine use across all EU-25 countries so that a
100% coverage rate of the target at-risk population could be
achieved
Current coverage
of at-risk population
35.4% coverage
100% coverage
Number vaccinated
79,054,065
223,442,807
Number of cases of influenza
18,391,577
~-7M
11,172,140
PCP visits for treatment of
influenza
5,119,959
~-2M
3,158,794
Hospital admission
3,075,911
~ - 0,8 M
2,279,169
133,542
~ - 70 K
65,005
Excess deaths
Ryan J, et al. Vaccine 2006; 24: 6812–6822.[121]
Conclusion
•
Influenza vaccine coverage rates among recommended
groups are well below the WHO goals
•
Implementation of appropriate vaccination policies can
positively influence uptake rates
•
Health cost of treating viral respiratory infections is
considerable
•
Reimbursing flu vaccination for 65+ in Poland can be
assumed cost-effective
•
Several factors would encourage vaccination and break
down obstacles to immunisation
–
Physician recommendation
–
Perception of the disease and the vaccine
–
Trust in the vaccine
–
Strong official recommendations
–
Free access to vaccine
46
Acknowledgments
• Patricia Blank, University of Basel and University of
Zurich
• Matthias Schwenkglenks, University of Basel
• Michael Endrich, Bern
• EVM
• Angus Nicoll, ECDC
47
Thank you for your attention!
48
Questions?
49
Contact
Thomas D. Szucs, MD MBA MPH LLM
T
+41 61 265 76 50
Institute of Pharmaceutical Medicine
F
+41 61 261 76 55
European Center of Pharmaceutical Medicine
E
[email protected]
University of Basel
W www.ecpm.ch;
www.szucs.ch
Klingelbergstrasse 61
CH-4056 Basel
50